CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial.

PubMed

Tong, Steven Y C; Nelson, Jane; Paterson, David L; Fowler, Vance G; Howden, Benjamin P; Cheng, Allen C; Chatfield, Mark; Lipman, Jeffrey; Van Hal, Sebastian; O'Sullivan, Matthew; Robinson, James O; Yahav, Dafna; Lye, David; Davis, Joshua S

2016-03-31

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20-50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. ClinicalTrials.gov Identifier: NCT02365493 . Registered 24 February 2015.

Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting

PubMed Central

Singer, Joseph; Shortt, Nicholas; Beasley, Richard; Salih, Shahlaa AL

2017-01-01

Introduction Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as ‘cold sores’, which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban). Methods and analysis This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. Ethics and dissemination New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants. Trial registration number Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results. SCOTT Registration: 15/SCOTT/14 Protocol version 4.0 (12 June 2017) PMID:28775197

The impact of a disease management program (COACH) on the attainment of better cardiovascular risk control in dyslipidaemic patients at primary care centres (The DISSEMINATE Study): a randomised controlled trial

PubMed Central

2012-01-01

Background To evaluate the efficacy of Counselling and Advisory Care for Health (COACH) programme in managing dyslipidaemia among primary care practices in Malaysia. This open-label, parallel, randomised controlled trial compared the COACH programme delivered by primary care physicians alone (PCP arm) and primary care physicians assisted by nurse educators (PCP-NE arm). Methods This was a multi-centre, open label, randomised trial of a disease management programme (COACH) among dyslipidaemic patients in 21 Malaysia primary care practices. The participating centres enrolled 297 treatment naïve subjects who had the primary diagnosis of dyslipidaemia; 149 were randomised to the COACH programme delivered by primary care physicians assisted by nurse educators (PCP-NE) and 148 to care provided by primary care physicians (PCP) alone. The primary efficacy endpoint was the mean percentage change from baseline LDL-C at week 24 between the 2 study arms. Secondary endpoints included mean percentage change from baseline of lipid profile (TC, LDL-C, HDL-C, TG, TC: HDL ratio), Framingham Cardiovascular Health Risk Score and absolute risk change from baseline in blood pressure parameters at week 24. The study also assessed the sustainability of programme efficacy at week 36. Results Both study arms demonstrated improvement in LDL-C from baseline. The least squares (LS) mean change from baseline LDL-C were −30.09% and −27.54% for PCP-NE and PCP respectively. The difference in mean change between groups was 2.55% (p=0.288), with a greater change seen in the PCP-NE arm. Similar observations were made between the study groups in relation to total cholesterol change at week 24. Significant difference in percentage change from baseline of HDL-C were observed between the PCP-NE and PCP groups, 3.01%, 95% CI 0.12-5.90, p=0.041, at week 24. There was no significant difference in lipid outcomes between 2 study groups at week 36 (12 weeks after the programme had ended). Conclusion Patients who received coaching and advice from primary care physicians (with or without the assistance by nurse educators) showed improvement in LDL-cholesterol. Disease management services delivered by PCP-NE demonstrated a trend towards add-on improvements in cholesterol control compared to care delivered by physicians alone; however, the improvements were not maintained when the services were withdrawn. Trial registration National Medical Research Registration (NMRR) Number: NMRR-08-287-1442 Trial Registration Number (ClinicalTrials.gov Identifier): NCT00708370 PMID:23046818

The impact of a disease management program (COACH) on the attainment of better cardiovascular risk control in dyslipidaemic patients at primary care centres (The DISSEMINATE Study): a randomised controlled trial.

PubMed

Selvaraj, Francis Jude; Mohamed, Mafauzy; Omar, Khairani; Nanthan, Sudha; Kusiar, Zainab; Subramaniam, Selvaraj Y; Ali, Norsiah; Karanakaran, Kamalakaran; Ahmad, Fauziah; Low, Wilson H H

2012-10-10

To evaluate the efficacy of Counselling and Advisory Care for Health (COACH) programme in managing dyslipidaemia among primary care practices in Malaysia. This open-label, parallel, randomised controlled trial compared the COACH programme delivered by primary care physicians alone (PCP arm) and primary care physicians assisted by nurse educators (PCP-NE arm). This was a multi-centre, open label, randomised trial of a disease management programme (COACH) among dyslipidaemic patients in 21 Malaysia primary care practices. The participating centres enrolled 297 treatment naïve subjects who had the primary diagnosis of dyslipidaemia; 149 were randomised to the COACH programme delivered by primary care physicians assisted by nurse educators (PCP-NE) and 148 to care provided by primary care physicians (PCP) alone. The primary efficacy endpoint was the mean percentage change from baseline LDL-C at week 24 between the 2 study arms. Secondary endpoints included mean percentage change from baseline of lipid profile (TC, LDL-C, HDL-C, TG, TC: HDL ratio), Framingham Cardiovascular Health Risk Score and absolute risk change from baseline in blood pressure parameters at week 24. The study also assessed the sustainability of programme efficacy at week 36. Both study arms demonstrated improvement in LDL-C from baseline. The least squares (LS) mean change from baseline LDL-C were -30.09% and -27.54% for PCP-NE and PCP respectively. The difference in mean change between groups was 2.55% (p=0.288), with a greater change seen in the PCP-NE arm. Similar observations were made between the study groups in relation to total cholesterol change at week 24. Significant difference in percentage change from baseline of HDL-C were observed between the PCP-NE and PCP groups, 3.01%, 95% CI 0.12-5.90, p=0.041, at week 24. There was no significant difference in lipid outcomes between 2 study groups at week 36 (12 weeks after the programme had ended). Patients who received coaching and advice from primary care physicians (with or without the assistance by nurse educators) showed improvement in LDL-cholesterol. Disease management services delivered by PCP-NE demonstrated a trend towards add-on improvements in cholesterol control compared to care delivered by physicians alone; however, the improvements were not maintained when the services were withdrawn. National Medical Research Registration (NMRR) Number: NMRR-08-287-1442Trial Registration Number (ClinicalTrials.gov Identifier): NCT00708370.

Assessing the effectiveness of a 3-month day-and-night home closed-loop control combined with pump suspend feature compared with sensor-augmented pump therapy in youths and adults with suboptimally controlled type 1 diabetes: a randomised parallel study protocol.

PubMed

Bally, Lia; Thabit, Hood; Tauschmann, Martin; Allen, Janet M; Hartnell, Sara; Wilinska, Malgorzata E; Exall, Jane; Huegel, Viki; Sibayan, Judy; Borgman, Sarah; Cheng, Peiyao; Blackburn, Maxine; Lawton, Julia; Elleri, Daniela; Leelarathna, Lalantha; Acerini, Carlo L; Campbell, Fiona; Shah, Viral N; Criego, Amy; Evans, Mark L; Dunger, David B; Kollman, Craig; Bergenstal, Richard M; Hovorka, Roman

2017-07-13

Despite therapeutic advances, many individuals with type 1 diabetes are unable to achieve tight glycaemic target without increasing the risk of hypoglycaemia. The objective of this study is to determine the effectiveness of a 3-month day-and-night home closed-loop glucose control combined with a pump suspend feature, compared with sensor-augmented insulin pump therapy in youths and adults with suboptimally controlled type 1 diabetes. The study adopts an open-label, multi-centre, multi-national (UK and USA), randomised, single-period, parallel design and aims for 84 randomised patients. Participants are youths (6-21 years) or adults (>21 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mol) and ≤10% (86 mmol/mol)). Following a 4-week run-in period, eligible participants will be randomised to a 3-month use of automated closed-loop insulin delivery combined with pump suspend feature or to sensor-augmented insulin pump therapy. Analyses will be conducted on an intention-to-treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3-month free-living phase. Secondary outcomes include HbA1c at 3 months, mean glucose, time spent below and above target; time with glucose levels <3.5 and <2.8 mmol/L; area under the curve when sensor glucose is <3.5 mmol/L, time with glucose levels >16.7 mmol/L, glucose variability; total, basal and bolus insulin dose and change in body weight. Participants' and their families' perception in terms of lifestyle change, daily diabetes management and fear of hypoglycaemia will be evaluated. Ethics/institutional review board approval has been obtained. Before screening, all participants/guardians will be provided with oral and written information about the trial. The study will be disseminated by peer-reviewed publications and conference presentations. NCT02523131; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Making food labels social: The impact of colour of nutritional labels and injunctive norms on perceptions and choice of snack foods☆

PubMed Central

Vasiljevic, Milica; Pechey, Rachel; Marteau, Theresa M.

2015-01-01

Recent studies report that using green labels to denote healthier foods, and red to denote less healthy foods increases consumption of green- and decreases consumption of red-labelled foods. Other symbols (e.g. emoticons conveying normative approval and disapproval) could also be used to signal the healthiness and/or acceptability of consuming such products. The present study tested the combined effects of using emoticons and colours on labels amongst a nationally representative sample of the UK population (n = 955). In a 3 (emoticon expression: smiling vs. frowning vs. no emoticon) × 3 (colour label: green vs. red vs. white) ×2 (food option: chocolate bar vs. cereal bar) between-subjects experiment, participants rated the level of desirability, healthiness, tastiness, and calorific content of a snack bar they had been randomised to view. At the end they were further randomised to view one of nine possible combinations of colour and emoticon labels and asked to choose between a chocolate and a cereal bar. Regardless of label, participants rated the chocolate as tastier and more desirable when compared to the cereal bar, and the cereal bar as healthier than the chocolate bar. A series of interactions revealed that a frowning emoticon on a white background decreased perceptions of healthiness and tastiness of the cereal bar, but not the chocolate bar. In the explicit choice task selection was unaffected by label. Overall nutritional labels had limited effects on perceptions and no effects on choice of snack foods. Emoticon labels yielded stronger effects on perceptions of taste and healthiness of snacks than colour labels. Frowning emoticons may be more potent than smiling emoticons at influencing the perceived healthiness and tastiness of foods carrying health halos. PMID:25841647

Symptoms and quality of life in patients with suspected angina undergoing CT coronary angiography: a randomised controlled trial

PubMed Central

Hunter, Amanda; Shah, Anoop; Assi, Valentina; Lewis, Stephanie; Mangion, Kenneth; Berry, Colin; Boon, Nicholas A; Clark, Elizabeth; Flather, Marcus; Forbes, John; McLean, Scott; Roditi, Giles; van Beek, Edwin JR; Timmis, Adam D; Newby, David E

2017-01-01

Background In patients with suspected angina pectoris, CT coronary angiography (CTCA) clarifies the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown. Methods In a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12. Results Baseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference −1.74 (95% CIs, −3.34 to −0.14), p=0.0329), angina frequency (difference −1.55 (−2.85 to −0.25), p=0.0198) and quality of life (difference −3.48 (−4.95 to −2.01), p<0.0001) at 6 months. For patients undergoing CTCA, improvements in symptoms were greatest in those diagnosed with normal coronary arteries or who had their preventative therapy discontinued, and least in those with moderate non-obstructive disease or had a new prescription of preventative therapy (p<0.001 for all). Conclusions While improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease. Trial registration number: NCT01149590. PMID:28246175

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial.

PubMed

Innerhofer, Petra; Fries, Dietmar; Mittermayr, Markus; Innerhofer, Nicole; von Langen, Daniel; Hell, Tobias; Gruber, Gottfried; Schmid, Stefan; Friesenecker, Barbara; Lorenz, Ingo H; Ströhle, Mathias; Rastner, Verena; Trübsbach, Susanne; Raab, Helmut; Treml, Benedikt; Wally, Dieter; Treichl, Benjamin; Mayr, Agnes; Kranewitter, Christof; Oswald, Elgar

2017-06-01

Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure. This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18-80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635. Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis. The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47-240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95-10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78-4·86], p=0·15). Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of pre- and post-operative physical activity on recovery after colorectal cancer surgery (PHYSSURG-C): study protocol for a randomised controlled trial.

PubMed

Onerup, Aron; Angenete, Eva; Bock, David; Börjesson, Mats; Fagevik Olsén, Monika; Grybäck Gillheimer, Elin; Skullman, Stefan; Thörn, Sven-Egron; Haglind, Eva; Nilsson, Hanna

2017-05-08

Surgery for colorectal cancer is associated with a high risk of post-operative adverse events, re-operations and a prolonged post-operative recovery. Previously, the effect of prehabilitation (pre-operative physical activity) has been studied for different types of surgery, including colorectal surgery. However, the trials on colorectal surgery have been of limited methodological quality and size. The aim of this trial is to compare the effect of a combined pre- and post-operative intervention of moderate aerobic physical activity and inspiratory muscle training (IMT) with standard care on post-operative recovery after surgery for colorectal cancer. We are conducting a randomised, controlled, parallel-group, open-label, multi-centre trial with physical recovery within 4 weeks after cancer surgery as the primary endpoint. Some 640 patients planned for surgery for colorectal cancer will be enrolled. The intervention consists of pre- and post-operative physical activity with increased daily aerobic activity of moderate intensity as well as IMT. In the control group, patients will be advised to continue their normal daily exercise routine. The primary outcome is patient-reported physical recovery 4 weeks post-operatively. Secondary outcomes are length of sick leave, complication rate and severity, length of hospital stay, re-admittances, re-operations, post-operative mental recovery, quality of life and mortality, as well as changes in insulin-like growth factor 1 and insulin-like growth factor-binding protein 3, perception of pain and a health economic analysis. An increase in moderate-intensity aerobic physical activity is a safe, cheap and feasible intervention that would be possible to implement in standard care for patients with colorectal cancer. If shown to be effective, this lifestyle intervention could be a clinical parallel to pre-operative smoke cessation that has already been implemented with good clinical results. ClinicalTrials.gov identifier: NCT02299596 . Registered on 17 November 2014.

Making food labels social: The impact of colour of nutritional labels and injunctive norms on perceptions and choice of snack foods.

PubMed

Vasiljevic, Milica; Pechey, Rachel; Marteau, Theresa M

2015-08-01

Recent studies report that using green labels to denote healthier foods, and red to denote less healthy foods increases consumption of green- and decreases consumption of red-labelled foods. Other symbols (e.g. emoticons conveying normative approval and disapproval) could also be used to signal the healthiness and/or acceptability of consuming such products. The present study tested the combined effects of using emoticons and colours on labels amongst a nationally representative sample of the UK population (n = 955). In a 3 (emoticon expression: smiling vs. frowning vs. no emoticon) × 3 (colour label: green vs. red vs. white) ×2 (food option: chocolate bar vs. cereal bar) between-subjects experiment, participants rated the level of desirability, healthiness, tastiness, and calorific content of a snack bar they had been randomised to view. At the end they were further randomised to view one of nine possible combinations of colour and emoticon labels and asked to choose between a chocolate and a cereal bar. Regardless of label, participants rated the chocolate as tastier and more desirable when compared to the cereal bar, and the cereal bar as healthier than the chocolate bar. A series of interactions revealed that a frowning emoticon on a white background decreased perceptions of healthiness and tastiness of the cereal bar, but not the chocolate bar. In the explicit choice task selection was unaffected by label. Overall nutritional labels had limited effects on perceptions and no effects on choice of snack foods. Emoticon labels yielded stronger effects on perceptions of taste and healthiness of snacks than colour labels. Frowning emoticons may be more potent than smiling emoticons at influencing the perceived healthiness and tastiness of foods carrying health halos. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.

PubMed

Bianchi, Maria Luisa; Colombo, Carla; Assael, Baroukh M; Dubini, Antonella; Lombardo, Mariangela; Quattrucci, Serena; Bella, Sergio; Collura, Mirella; Messore, Barbara; Raia, Valeria; Poli, Furio; Bini, Rita; Albanese, Carlina V; De Rose, Virginia; Costantini, Diana; Romano, Giovanna; Pustorino, Elena; Magazzù, Giuseppe; Bertasi, Serenella; Lucidi, Vincenzina; Traverso, Gabriella; Coruzzo, Anna; Grzejdziak, Amelia D

2013-07-01

Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, five patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not differ significantly for other adverse events. Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fibrosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and effectively increase bone mineral density. Telethon Foundation (Italy). Copyright © 2013 Elsevier Ltd. All rights reserved.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis.

PubMed

Lichtenstein, Gary R; Travis, Simon; Danese, Silvio; D'Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J

2015-09-01

Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9 mg, 6 mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9 mg or placebo for 4 weeks, then open-label budesonide MMX 9 mg for 4 weeks]; and one open-label study [budesonide MMX 9 mg for 8 weeks] were pooled. Patients randomised to budesonide MMX 9 mg [n = 288], 6 mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9 mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Budesonide MMX 9 mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis

PubMed Central

Travis, Simon; Danese, Silvio; D’Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E. David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J.

2015-01-01

Background and aims: Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Methods: Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9mg, 6mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9mg or placebo for 4 weeks, then open-label budesonide MMX 9mg for 4 weeks]; and one open-label study [budesonide MMX 9mg for 8 weeks] were pooled. Results: Patients randomised to budesonide MMX 9mg [n = 288], 6mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Conclusions: Budesonide MMX 9mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. PMID:26094251

Effectiveness of a cough management algorithm at the transitional phase from acute to chronic cough in Australian children aged <15 years: protocol for a randomised controlled trial.

PubMed

O'Grady, Kerry-Ann F; Grimwood, Keith; Toombs, Maree; Sloots, Theo P; Otim, Michael; Whiley, David; Anderson, Jennie; Rablin, Sheree; Torzillo, Paul J; Buntain, Helen; Connor, Anne; Adsett, Don; Meng Kar, Oon; Chang, Anne B

2017-03-03

Acute respiratory infections (ARIs) are leading causes of hospitalisation in Australian children and, if recurrent, are associated with increased risk of chronic pulmonary disorders later in life. Chronic (>4 weeks) cough in children following ARI is associated with decreased quality-of-life scores and increased health and societal economic costs. We will determine whether a validated evidence-based cough algorithm, initiated when chronic cough is first diagnosed after presentation with ARI, improves clinical outcomes in children compared with usual care. A multicentre, parallel group, open-label, randomised controlled trial, nested within a prospective cohort study in Southeast Queensland, Australia, is underway. 750 children aged <15 years will be enrolled and followed weekly for 8 weeks after presenting with an ARI with cough. 214 children from this cohort with persistent cough at day 28 will be randomised to either early initiation of a cough management algorithm or usual care (107 per group). Randomisation is stratified by reason for presentation, site and total cough duration at day 28 (<6 and ≥6 weeks). Demographic details, risk factors, clinical histories, examination findings, cost-of-illness data, an anterior nasal swab and parent and child exhaled carbon monoxide levels (when age appropriate) are collected at enrolment. Weekly contacts will collect cough status and cost-of-illness data. Additional nasal swabs are collected at days 28 and 56. The primary outcome is time-to-cough resolution. Secondary outcomes include direct and indirect costs of illness and the predictors of chronic cough postpresentation. The Children's Health Queensland (HREC/15/QRCH/15) and the Queensland University of Technology University (1500000132) Research Ethics Committees have approved the study. The study will inform best-practice management of cough in children. ACTRN12615000132549. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Predictors of retention in a randomised trial of smoking cessation in low-socioeconomic status Australian smokers.

PubMed

Courtney, Ryan J; Clare, Philip; Boland, Veronica; Martire, Kristy A; Bonevski, Billie; Hall, Wayne; Siahpush, Mohammad; Borland, Ron; Doran, Christopher M; West, Robert; Farrell, Michael; Mattick, Richard P

2017-01-01

Little is known about the factors associated with retention in smoking cessation trials, especially for low-socioeconomic status (low-SES) smokers. This study examined the factors associated with retention of low-SES smokers in the Australian Financial Interventions for Smoking Cessation Among Low-Income Smokers (FISCALS) trial. A two-group parallel block randomised open-label trial with allocation concealment. Australia. The study was conducted primarily by telephone-based interviews with nicotine replacement therapy delivered via mail. 1047 low-SES smokers interested in quitting smoking were randomised. Participants completed computer assisted telephone interviews (CATIs) at baseline, 2-month and 8-month follow-up. Smoking-related, substance use, mental or physical health, general psychological constructs, sociodemographic and recruitment sources association with retention at 8-month follow-up were examined using binary logistic regression. 946 participants (90%) completed the 2-month follow-up interview and 880 participants (84%) completed the 8-month follow-up interview. Retention at 8-months was associated with higher motivation to quit (OR: 1.15; 95% CI: 1.04, 1.27 p<0.01), more recent quit attempts (OR: 1.20; 95% CI: 1.04, 1.40 p<0.05), increasing age (OR: 1.05; 95% CI: 1.03, 1.07 p<0.01), and higher level of education (OR: 2.24; 95% CI: 1.45, 3.46 p<0.01). Lower retention at 8-months occurred for those participants recruited from posters placed in Department of Human Service Centrelink Offices (OR: 0.56; 95% CI: 0.35, 0.89, p<0.05) compared to participants recruited from Quitline services. No significant differences in retention were found for participants recruited via newspaper advertisements or word of mouth compared to Quitline services. No significant associations were found between health-related or behavioural factors and retention. In the context of high overall retention rates from disadvantaged smokers in a randomised trial, retention was greater in those smokers with higher motivation to quit, more recent quit attempts, increased age, higher level of education and for those recruited through Quitline or newspaper advertisements. Copyright © 2016 Elsevier Ltd. All rights reserved.

PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group.

PubMed

Borchmann, Peter; Goergen, Helen; Kobe, Carsten; Lohri, Andreas; Greil, Richard; Eichenauer, Dennis A; Zijlstra, Josée M; Markova, Jana; Meissner, Julia; Feuring-Buske, Michaela; Hüttmann, Andreas; Dierlamm, Judith; Soekler, Martin; Beck, Hans-Joachim; Willenbacher, Wolfgang; Ludwig, Wolf-Dieter; Pabst, Thomas; Topp, Max S; Hitz, Felicitas; Bentz, Martin; Keller, Ulrich Bernd; Kühnhardt, Dagmar; Ostermann, Helmut; Schmitz, Norbert; Hertenstein, Bernd; Aulitzky, Walter; Maschmeyer, Georg; Vieler, Tom; Eich, Hans; Baues, Christian; Stein, Harald; Fuchs, Michael; Kuhnert, Georg; Diehl, Volker; Dietlein, Markus; Engert, Andreas

2018-12-23

The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is very active in patients with advanced-stage Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual patients might be cured with less burdensome therapy. We investigated whether metabolic response determined by PET after two cycles of standard regimen eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for PET-2-positive patients and reducing it for PET-2-negative patients. In this open-label, randomised, parallel-group phase 3 trial, we recruited patients aged 18-60 years with newly diagnosed, advanced-stage Hodgkin's lymphoma in 301 hospitals and private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. After central review of PET-2, patients were assigned (1:1) to one of two parallel treatment groups on the basis of their PET-2 result. Patients with positive PET-2 were randomised to receive six additional cycles of either standard eBEACOPP (8 × eBEACOPP in total) or eBEACOPP with rituximab (8 × R-eBEACOPP). Those with negative PET-2 were randomised between standard treatment with six additional cycles of eBEACOPP (8 × eBEACOPP) or experimental treatment with two additional cycles (4 × eBEACOPP). A protocol amendment in June, 2011, introduced a reduction of standard therapy to 6 × eBEACOPP; after this point, patients with positive PET-2 were no longer randomised and were all assigned to receive 6 × eBEACOPP and patients with negative PET-2 were randomly assigned to 6 × eBEACOPP (standard) or 4 × eBEACOPP (experimental). Randomisation was done centrally using the minimisation method including a random component, stratified according to centre, age (<45 vs ≥45 years), stage (IIB, IIIA vs IIIB, IV), international prognostic score (0-2 vs 3-7), and sex. eBEACOPP was given as previously described; rituximab was given intravenously at a dose of 375 mg/m 2 (maximum total dose 700 mg). The primary objectives were to show superiority of the experimental treatment in the PET-2-positive cohort, and to show non-inferiority of the experimental treatment in the PET-2-negative cohort in terms of the primary endpoint, progression-free survival. We defined non-inferiority as an absolute difference of 6% in the 5-year progression-free survival estimates. Primary analyses in the PET-2-negative cohort were per protocol; all other analyses were by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00515554. Between May 14, 2008, and July 18, 2014, we recruited 2101 patients, of whom 137 were found ineligible before randomisation and a further 19 were found ineligible after randomisation. Among 434 randomised patients (217 per arm) with positive PET-2, 5-year progression-free survival was 89·7% (95% CI 85·4-94·0) with eBEACOPP and 88·1% (83·5-92·7) with R-eBEACOPP (log-rank p=0·46). Patients with negative PET-2 randomly assigned to either 8 × eBEACOPP or 6 × eBEACOPP (n=504) or 4 × eBEACOPP (n=501) had 5-year progression-free survival of 90·8% (95% CI 87·9-93·7) and 92·2% (89·4-95·0), respectively (difference 1·4%, 95% CI -2·7 to 5·4). 4 × eBEACOPP was associated with fewer severe infections (40 [8%] of 498 vs 75 [15%] of 502) and organ toxicities (38 [8%] of 498 vs 91 [18%] of 502) than were 8 × eBEACOPP or 6 × eBEACOPP in PET-2-negative patients. Ten treatment-related deaths occurred: four in the PET-2-positive cohort (one [<1%] in the 8 × eBEACOPP group, three [1%] in the 8 × R-eBEACOPP group) and six in the PET-2-negative group (six [1%] in the 8 × eBEACOPP or 6 × eBEACOPP group). The favourable outcome of patients treated with eBEACOPP could not be improved by adding rituximab after positive PET-2. PET-2 negativity allows reduction to only four cycles of eBEACOPP without loss of tumour control. PET-2-guided eBEACOPP provides outstanding efficacy for all patients and increases overall survival by reducing treatment-related risks for patients with negative PET-2. We recommend this PET-2-guided treatment strategy for patients with advanced-stage Hodgkin's lymphoma. Deutsche Krebshilfe, Swiss State Secretariat for Education and Research, and Roche Pharma AG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protocol for a pilot randomised controlled trial of an intervention to increase the use of traffic light food labelling in UK shoppers (the FLICC trial).

PubMed

Scarborough, Peter; Hodgkins, Charo; Raats, Monique M; Harrington, Richard A; Cowburn, Gill; Dean, Moira; Doherty, Aiden; Foster, Charlie; Juszczak, Edmund; Matthews, Anne; Mizdrak, Anja; Mhurchu, Cliona Ni; Shepherd, Richard; Tiomotijevic, Lada; Winstone, Naomi; Rayner, Mike

2015-01-01

Traffic light labelling of foods-a system that incorporates a colour-coded assessment of the level of total fat, saturated fat, sugar and salt on the front of packaged foods-has been recommended by the UK Government and is currently in use or being phased in by many UK manufacturers and retailers. This paper describes a protocol for a pilot randomised controlled trial of an intervention designed to increase the use of traffic light labelling during real-life food purchase decisions. The objectives of this two-arm randomised controlled pilot trial are to assess recruitment, retention and data completion rates, to generate potential effect size estimates to inform sample size calculations for the main trial and to assess the feasibility of conducting such a trial. Participants will be recruited by email from a loyalty card database of a UK supermarket chain. Eligible participants will be over 18 and regular shoppers who frequently purchase ready meals or pizzas. The intervention is informed by a review of previous interventions encouraging the use of nutrition labelling and the broader behaviour change literature. It is designed to impact on mechanisms affecting belief and behavioural intention formation as well as those associated with planning and goal setting and the adoption and maintenance of the behaviour of interest, namely traffic light label use during purchases of ready meals and pizzas. Data will be collected using electronic sales data via supermarket loyalty cards and web-based questionnaires and will be used to estimate the effect of the intervention on the nutrition profile of purchased ready meals and pizzas and the behavioural mechanisms associated with label use. Data collection will take place over 48 weeks. A process evaluation including semi-structured interviews and web analytics will be conducted to assess feasibility of a full trial. The design of the pilot trial allows for efficient recruitment and data collection. The intervention could be generalised to a wider population if shown to be feasible in the main trial. ISRCTN: ISRCTN19316955.

Comparison of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus.

PubMed

Fang, Fu-Sheng; Gong, Yan-Ping; Li, Chun-Lin; Li, Jian; Tian, Hui; Huang, Wei; Wang, Liang-Chen; Li, Lin

2014-06-01

We aimed to compare the effect of repaglinide and metformin monotherapy as an initial therapy in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). In this 15-week, open-labelled, parallel-controlled, randomised study, 60 Chinese drug-naive patients with newly diagnosed T2DM were randomised (2:1) to receive repaglinide or metformin monotherapy. Primary endpoint was change in HbA1c from baseline to the end of the trial. Secondary endpoints included changes in glycaemic variability, insulin sensitivity and β-cell function. Patients in both repaglinide and metformin groups achieved significant reductions in HbA1c (-1.8 ± 1.5 vs -1.6 ± 1.5%), FPG (fasting blood glucose) (-1.7 ± 1.7 vs -2.1 ± 1.7  mmol/l) and 2-h PPG (post-prandial glucose) (-3.8 ± 3.1 vs -3.8 ± 3.6  mmol/l), with no statistical differences between the groups. Glycaemic variability, glucose infusion rate and β-cell function were all significantly improved from baseline in the two groups (all P<0.05), without any statistical differences in the improvement between the groups. Repaglinide and metformin achieved comparable efficacy in improving glycaemic control, reducing glycaemic variability, enhancing insulin sensitivity and ameliorating β-cell function. Therefore, repaglinide is an optional agent for initial therapy in Chinese patients with newly diagnosed T2DM. © 2014 European Society of Endocrinology.

Genetic polymorphisms and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets.

PubMed

Sørensen, Thorkild I A; Boutin, Philippe; Taylor, Moira A; Larsen, Lesli H; Verdich, Camilla; Petersen, Liselotte; Holst, Claus; Echwald, Søren M; Dina, Christian; Toubro, Søren; Petersen, Martin; Polak, Jan; Clément, Karine; Martínez, J Alfredo; Langin, Dominique; Oppert, Jean-Michel; Stich, Vladimir; Macdonald, Ian; Arner, Peter; Saris, Wim H M; Pedersen, Oluf; Astrup, Arne; Froguel, Philippe

2006-06-01

To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. Randomised, parallel, two-arm, open-label multi-centre trial. Eight clinical centres in seven European countries. 771 obese adult individuals. 10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants. WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.

What do we know about the effects of exposure to 'Low alcohol' and equivalent product labelling on the amounts of alcohol, food and tobacco people select and consume? A systematic review.

PubMed

Shemilt, Ian; Hendry, Vivien; Marteau, Theresa M

2017-01-12

Explicit labelling of lower strength alcohol products could reduce alcohol consumption by attracting more people to buy and drink such products instead of higher strength ones. Alternatively, it may lead to more consumption due to a 'self-licensing' mechanism. Equivalent labelling of food or tobacco (for example "Low fat" or "Low tar") could influence consumption of those products by similar mechanisms. This systematic review examined the effects of 'Low alcohol' and equivalent labelling of alcohol, food and tobacco products on selection, consumption, and perceptions of products among adults. A systematic review was conducted based on Cochrane methods. Electronic and snowball searches identified 26 eligible studies. Evidence from 12 randomised controlled trials (all on food) was assessed for risk of bias, synthesised using random effects meta-analysis, and interpreted in conjunction with evidence from 14 non-randomised studies (one on alcohol, seven on food and six on tobacco). Outcomes assessed were: quantities of the product (i) selected or (ii) consumed (primary outcomes - behaviours), (iii) intentions to select or consume the product, (iv) beliefs associated with it consumption, (v) product appeal, and (vi) understanding of the label (secondary outcomes - cognitions). Evidence for impacts on the primary outcomes (i.e. amounts selected or consumed) was overall of very low quality, showing mixed effects, likely to vary by specific label descriptors, products and population characteristics. Overall very low quality evidence suggested that exposure to 'Low alcohol' and equivalent labelling on alcohol, food and tobacco products can shift consumer perceptions of products, with the potential to 'self-licence' excess consumption. Considerable uncertainty remains about the effects of labels denoting low alcohol, and equivalent labels, on alcohol, food and tobacco selection and consumption. Independent, high-quality studies are urgently needed to inform policies on labelling regulations.

Protease inhibitor monotherapy for long-term management of HIV infection: a randomised, controlled, open-label, non-inferiority trial

PubMed Central

Paton, Nicholas I; Stöhr, Wolfgang; Arenas-Pinto, Alejandro; Fisher, Martin; Williams, Ian; Johnson, Margaret; Orkin, Chloe; Chen, Fabian; Lee, Vincent; Winston, Alan; Gompels, Mark; Fox, Julie; Scott, Karen; Dunn, David T

2015-01-01

Summary Background Standard-of-care antiretroviral therapy (ART) uses a combination of drugs deemed essential to minimise treatment failure and drug resistance. Protease inhibitors are potent, with a high genetic barrier to resistance, and have potential use as monotherapy after viral load suppression is achieved with combination treatment. We aimed to assess clinical risks and benefits of protease inhibitor monotherapy in long-term clinical use: in particular, the effect on drug resistance and future treatment options. Methods In this pragmatic, parallel-group, randomised, controlled, open-label, non-inferiority trial, we enrolled adults (≥18 years of age) positive for HIV attending 43 public sector treatment centres in the UK who had suppressed viral load (<50 copies per mL) for at least 24 weeks on combination ART with no change in the previous 12 weeks and a CD4 count of more than 100 cells per μL. Participants were randomly allocated (1:1) to maintain ongoing triple therapy (OT) or to switch to a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy (PI-mono); we recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir (100 mg)-boosted lopinavir (400 mg) twice daily, with prompt return to combination treatment if viral load rebounded. All treatments were oral. Randomisation was with permuted blocks of varying size and stratified by centre and baseline ART; we used a computer-generated, sequentially numbered randomisation list. The primary outcome was loss of future drug options, defined as new intermediate-level or high-level resistance to one or more drugs to which the patient's virus was deemed sensitive at trial entry (assessed at 3 years; non-inferiority margin of 10%). We estimated probability of rebound and resistance with Kaplan-Meier analysis. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN04857074. Findings Between Nov 4, 2008, and July 28, 2010, we randomly allocated 587 participants to OT (291) or PI-mono (296). At 3 years, one or more future drug options had been lost in two participants (Kaplan-Meier estimate 0·7%) in the OT group and six (2·1%) in the PI-mono group: difference 1·4% (−0·4 to 3·4); non-inferiority shown. 49 (16·8%) participants in the OT group and 65 (22·0%) in the PI-mono group had grade 3 or 4 clinical adverse events (difference 5·1% [95% CI −1·3 to 11·5]; p=0·12); 45 (six treatment related) and 56 (three treatment related) had serious adverse events. Interpretation Protease inhibitor monotherapy, with regular viral load monitoring and prompt reintroduction of combination treatment for rebound, preserved future treatment options and did not change overall clinical outcomes or frequency of toxic effects. Protease inhibitor monotherapy is an acceptable alternative for long-term clinical management of HIV infection. Funding National Institute for Health Research. PMID:26423649

Optimal tracers for parallel labeling experiments and 13C metabolic flux analysis: A new precision and synergy scoring system.

PubMed

Crown, Scott B; Long, Christopher P; Antoniewicz, Maciek R

2016-11-01

13 C-Metabolic flux analysis ( 13 C-MFA) is a widely used approach in metabolic engineering for quantifying intracellular metabolic fluxes. The precision of fluxes determined by 13 C-MFA depends largely on the choice of isotopic tracers and the specific set of labeling measurements. A recent advance in the field is the use of parallel labeling experiments for improved flux precision and accuracy. However, as of today, no systemic methods exist for identifying optimal tracers for parallel labeling experiments. In this contribution, we have addressed this problem by introducing a new scoring system and evaluating thousands of different isotopic tracer schemes. Based on this extensive analysis we have identified optimal tracers for 13 C-MFA. The best single tracers were doubly 13 C-labeled glucose tracers, including [1,6- 13 C]glucose, [5,6- 13 C]glucose and [1,2- 13 C]glucose, which consistently produced the highest flux precision independent of the metabolic flux map (here, 100 random flux maps were evaluated). Moreover, we demonstrate that pure glucose tracers perform better overall than mixtures of glucose tracers. For parallel labeling experiments the optimal isotopic tracers were [1,6- 13 C]glucose and [1,2- 13 C]glucose. Combined analysis of [1,6- 13 C]glucose and [1,2- 13 C]glucose labeling data improved the flux precision score by nearly 20-fold compared to widely use tracer mixture 80% [1- 13 C]glucose +20% [U- 13 C]glucose. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple intravenous administrations: an open-label randomised controlled trial.

PubMed

Sörgel, Fritz; Thyroff-Friesinger, Ursula; Vetter, Andrea; Vens-Cappell, Bernhard; Kinzig, Martina

2009-05-22

HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations. An open, randomised, parallel group study was conducted in 80 healthy adult males. Subjects were randomised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation. The haematological profiles of both treatments were similar, as determined from their population mean curves and the AUECHb ratio and 90% confidence interval (99.9% [98.5-101.2%]), the primary pharmacodynamic endpoint of this study. The pharmacokinetic parameters after the treatments showed minor differences after single dosing, but not at steady state doses. After multiple doses, HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin (AUCtau ratio and 90% confidence interval: 89.2% [82.5-96.2%]). Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected. HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action. This supports the conclusion that HX575 and the comparator epoetin alfa, when administered intraveneously, will be equally efficacious and may be interchangeable as therapy.

Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial.

PubMed

Rintoul, Robert C; Ritchie, Andrew J; Edwards, John G; Waller, David A; Coonar, Aman S; Bennett, Maxine; Lovato, Eleonora; Hughes, Victoria; Fox-Rushby, Julia A; Sharples, Linda D

2014-09-20

Malignant pleural mesothelioma incidence continues to rise, with few available evidence-based therapeutic options. Results of previous non-randomised studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP) might improve symptom control and survival. We aimed to compare efficacy in terms of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma. We undertook an open-label, parallel-group, randomised, controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion, recruited from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to either VAT-PP or talc pleurodesis by computer-generated random numbers, stratified by European Organisation for Research and Treatment of Cancer risk category (high vs low). The primary outcome was overall survival at 1 year, analysed by intention to treat (all patients randomly assigned to a treatment group with a final diagnosis of mesothelioma). This trial is registered with ClinicalTrials.gov, number NCT00821860. Between Oct 24, 2003, and Jan 24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc pleurodesis group (hazard ratio 1·04 [95% CI 0·76-1·42]; p=0·81). Surgical complications were significantly more common after VAT-PP than after talc pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten (14%) of 73 patients who completed talc pleurodesis (p=0·019), as were respiratory complications (19 [24%] vs 11 [15%]; p=0·22) and air-leak beyond 10 days (five [6%] vs one [1%]; p=0·21), although not significantly so. Median hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP compared with 3 days (2-5) for those who received talc pleurodesis (p<0·0001). VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment. BUPA Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care.

PubMed

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Hollinghurst, Sandra; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-11-16

To determine the feasibility of a randomised controlled trial of 'leave on' emollients for children with eczema. Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. General practices in the UK. Children with eczema aged 1 month to <5 years. Primary outcome-proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes-participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. 197 children were recruited-107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic ('app') form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. ISRCTN21828118/EudraCT2013-003001-26. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Choice of Moisturiser for Eczema Treatment (COMET): feasibility study of a randomised controlled parallel group trial in children recruited from primary care

PubMed Central

Ridd, Matthew J; Garfield, Kirsty; Gaunt, Daisy M; Redmond, Niamh M; Powell, Kingsley; Wilson, Victoria; Guy, Richard H; Ball, Nicola; Shaw, Lindsay; Purdy, Sarah; Metcalfe, Chris

2016-01-01

Objectives To determine the feasibility of a randomised controlled trial of ‘leave on’ emollients for children with eczema. Design Single-centre, pragmatic, 4-arm, observer-blinded, parallel, randomised feasibility trial. Setting General practices in the UK. Participants Children with eczema aged 1 month to <5 years. Outcome measures Primary outcome—proportion of parents who reported use of the allocated study emollient every day for the duration of follow-up (12 weeks). Other feasibility outcomes—participant recruitment and retention, data collection and completeness and blinding of observers to allocation. Interventions Aveeno lotion, Diprobase cream, Doublebase gel, Hydromol ointment. Results 197 children were recruited—107 by self-referral (mainly via practice mail-outs) and 90 by inconsultation (clinician consenting and randomising) pathways. Participants recruited inconsultation were younger, had more severe Patient-Oriented Eczema Measure scores and were more likely to withdraw than self-referrals. Parents of 20 (10%) of all the randomised participants reported using the allocated emollient daily for 84 days. The use of other non-study emollients was common. Completeness of data collected by parent-held daily diaries and at monthly study visits was good. Daily diaries were liked (81%) but mainly completed on paper rather than via electronic (‘app’) form. Major costs drivers were general practitioner consultations and eczema-related prescriptions. Observer unblinding was infrequent, and occurred at the baseline or first follow-up visit through accidental disclosure. Conclusions It is feasible in a primary care setting to recruit and randomise young children with eczema to emollients, follow them up and collect relevant trial data, while keeping observers blinded to their allocation. However, reported use of emollients (study and others) has design implications for future trials. Trial registration number ISRCTN21828118/EudraCT2013-003001-26. PMID:27852708

A randomised controlled trial of clinics in secondary schools for adolescents with asthma.

PubMed Central

Salisbury, Chris; Francis, Caia; Rogers, Chris; Parry, Kate; Thomas, Huw; Chadwick, Stephanie; Turton, Pat

2002-01-01

AIM: To compare a nurse-led clinic in schools versus care in general practice for adolescents with asthma. DESIGN OF STUDY: Randomised controlled trial in four schools; parallel observational study in two schools. SETTING: Six comprehensive schools. METHOD: In the randomised trial, pupils were invited to attend asthma review at a nurse-led clinic either in school, or in general practice. The parallel observational study compared pupils invited to practice care within and outside the randomised trial. Primary outcome measures were attendance for asthma review, symptom control, and quality of life. Secondary outcomes were knowledge, attitudes, inhaler technique, use of steroids, school absence, peak flow rate, preference for future care, health service utilisation, and costs. RESULTS: School clinic pupils were more likely to attend an asthma review than those randomised to practice care (90.8% versus 51.0% overall [P < 0.001, not consistent across schools]). No differences were observed in symptom control (P = 0.42) or quality of life (P = 0.63). Pupils attending school clinics had greater knowledge of asthma (difference = +0.38, 95% CI = 0.19 to 0.56), more positive attitudes (difference = +0.21, 95% CI = 0.05 to 0.36), and better inhaler technique (P < 0.001, not consistent across all schools). No differences were observed in school absence or peak flow rate. A majority (63%) of those who had received care at school preferred this model in future. Median costs of providing care at school and at the practice were 32.10 Pounds and 19.80 Pounds, respectively. No differences were observed between the groups in the observational comparison on any outcome. CONCLUSIONS: The schools asthma clinic increased uptake of asthma reviews. There were improvements in various process measures, but not in clinical outcomes. PMID:12528584

Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting.

PubMed

Breitenstein, Caterina; Grewe, Tanja; Flöel, Agnes; Ziegler, Wolfram; Springer, Luise; Martus, Peter; Huber, Walter; Willmes, Klaus; Ringelstein, E Bernd; Haeusler, Karl Georg; Abel, Stefanie; Glindemann, Ralf; Domahs, Frank; Regenbrecht, Frank; Schlenck, Klaus-Jürgen; Thomas, Marion; Obrig, Hellmuth; de Langen, Ernst; Rocker, Roman; Wigbers, Franziska; Rühmkorf, Christina; Hempen, Indra; List, Jonathan; Baumgaertner, Annette

2017-04-15

Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam-Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (-0·03 points [4·04]; -0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

PubMed Central

Azzopardi, Denis; Robertson, Nicola J; Bainbridge, Alan; Cady, Ernest; Charles-Edwards, Geoffrey; Deierl, Aniko; Fagiolo, Gianlorenzo; Franks, Nicholas P; Griffiths, James; Hajnal, Joseph; Juszczak, Edmund; Kapetanakis, Basil; Linsell, Louise; Maze, Mervyn; Omar, Omar; Strohm, Brenda; Tusor, Nora; Edwards, A David

2016-01-01

Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. Funding UK Medical Research Council. PMID:26708675

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

PubMed Central

Aga, Anna-Birgitte; Olsen, Inge Christoffer; Lillegraven, Siri; Hammer, Hilde B; Uhlig, Till; Fremstad, Hallvard; Madland, Tor Magne; Lexberg, Åse Stavland; Haukeland, Hilde; Rødevand, Erik; Høili, Christian; Stray, Hilde; Noraas, Anne; Hansen, Inger Johanne Widding; Bakland, Gunnstein; Nordberg, Lena Bugge; van der Heijde, Désirée; Kvien, Tore K

2016-01-01

Objective To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants 238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions 122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results 26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration Clinical trials NCT01205854. PMID:27530741

Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial.

PubMed

Watson, Angus J M; Hudson, Jemma; Wood, Jessica; Kilonzo, Mary; Brown, Steven R; McDonald, Alison; Norrie, John; Bruhn, Hanne; Cook, Jonathan A

2016-11-12

Two commonly performed surgical interventions are available for severe (grade II-IV) haemorrhoids; traditional excisional surgery and stapled haemorrhoidopexy. Uncertainty exists as to which is most effective. The eTHoS trial was designed to establish the clinical effectiveness and cost-effectiveness of stapled haemorrhoidopexy compared with traditional excisional surgery. The eTHoS trial was a large, open-label, multicentre, parallel-group, pragmatic randomised controlled trial done in adult participants (aged 18 years or older) referred to hospital for surgical treatment for grade II-IV haemorrhoids. Participants were randomly assigned (1:1) to receive either traditional excisional surgery or stapled haemorrhoidopexy. Randomisation was minimised according to baseline EuroQol 5 dimensions 3 level score (EQ-5D-3L), haemorrhoid grade, sex, and centre with an automated system to stapled haemorrhoidopexy or traditional excisional surgery. The primary outcome was area under the quality of life curve (AUC) measured with the EQ-5D-3L descriptive system over 24 months, assessed according to the randomised groups. The primary outcome measure was analysed using linear regression with adjustment for the minimisation variables. This trial is registered with the ISRCTN registry, number ISRCTN80061723. Between Jan 13, 2011, and Aug 1, 2014, 777 patients were randomised (389 to receive stapled haemorrhoidopexy and 388 to receive traditional excisional surgery). Stapled haemorrhoidopexy was less painful than traditional excisional surgery in the short term and surgical complication rates were similar between groups. The EQ-5D-3L AUC score was higher in the traditional excisional surgery group than the stapled haemorrhoidopexy group over 24 months; mean difference -0·073 (95% CI -0·140 to -0·006; p=0·0342). EQ-5D-3L was higher for stapled haemorrhoidopexy in the first 6 weeks after surgery, the traditional excisional surgery group had significantly better quality of life scores than the stapled haemorrhoidopexy group. 24 (7%) of 338 participants who received stapled haemorrhoidopexy and 33 (9%) of 352 participants who received traditional excisional surgery had serious adverse events. As part of a tailored management plan for haemorrhoids, traditional excisional surgery should be considered over stapled haemorrhoidopexy as the surgical treatment of choice. National Institute for Health Research Health Technology Assessment programme. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Autologous platelet-rich plasma in the treatment of venous leg ulcers in primary care: a randomised controlled, pilot study.

PubMed

Burgos-Alonso, Natalia; Lobato, Igone; Hernández, Igone; Sebastian, Kepa San; Rodríguez, Begoña; March, Anna Giné; Perez-Salvador, Adriana; Arce, Veronica; Garcia-Alvarez, Arturo; Gomez-Fernandez, Maria Cruz; Grandes, Gonzalo; Andia, Isabel

2018-06-01

To examine the potential efficacy and safety of autologous platelet-rich plasma (PRP) in comparison with the conventional treatment (standard care, SoC) for the treatment of leg ulcers in patients with chronic venous insufficiency, in a primary health-care setting. A Phase I-II, open-label, parallel-group, multicentre, randomised pilot study was conducted. The outcome variables at baseline and at weeks five and nine included reduction in the ulcer area, Chronic Venous Insufficiency Quality of Life Questionnaire score, cost of the treatment for up to nine weeks and average weekly cure rate. A total of eight patients, each with at least a six-month history of venous leg ulcer (VLUs), were included in the study. A total of 12 ulcers were treated with either autologous PRP or standard SoC. Patients treated with PRP required wound care only once per week. In the SoC group, patients required intervention 2-3 times per week. A reduction in the mean ulcer size in the PRP group was 3.9cm 2 compared with the SoC group at 3.2cm 2 , although the sample size was insufficient to reach statistical significance. Improvement in quality of life (QoL) score was observed in the patients in the PRP group. This study offers proof-of-concept of the feasibility and safety of PRP treatment to inform larger clinical trials in patients with VLUs. Our preliminary results suggest that PRP delivers a safe and effective treatment for VLU care that can be implemented in primary health-care settings.

Genetic Polymorphisms and Weight Loss in Obesity: A Randomised Trial of Hypo-Energetic High- versus Low-Fat Diets

PubMed Central

Sørensen, Thorkild I. A; Boutin, Philippe; Taylor, Moira A; Larsen, Lesli H; Verdich, Camilla; Petersen, Liselotte; Holst, Claus; Echwald, Søren M; Dina, Christian; Toubro, Søren; Petersen, Martin; Polak, Jan; Clément, Karine; Martínez, J. Alfredo; Langin, Dominique; Oppert, Jean-Michel; Stich, Vladimir; Macdonald, Ian; Arner, Peter; Saris, Wim H. M; Pedersen, Oluf; Astrup, Arne; Froguel, Philippe

2006-01-01

Objectives: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. Design: Randomised, parallel, two-arm, open-label multi-centre trial. Setting: Eight clinical centres in seven European countries. Participants: 771 obese adult individuals. Interventions: 10-wk dietary intervention to hypo-energetic (−600 kcal/d) diets with a targeted fat energy of 20%–25% or 40%–45%, completed in 648 participants. Outcome Measures: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. Results: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from −0.6 to 0.8 kg, and homozygotes, from −0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to −1.6 kg in heterozygotes, and from 3.8 kg to −2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. Conclusions: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet. PMID:16871334

Two parallel, pragmatic, UK multicentre, randomised controlled trials comparing surgical options for upper compartment (vault or uterine) pelvic organ prolapse (the VUE Study): study protocol for a randomised controlled trial.

PubMed

Glazener, Cathryn; Constable, Lynda; Hemming, Christine; Breeman, Suzanne; Elders, Andrew; Cooper, Kevin; Freeman, Robert; Smith, Anthony R B; Hagen, Suzanne; McDonald, Alison; McPherson, Gladys; Montgomery, Isobel; Kilonzo, Mary; Boyers, Dwayne; Goulao, Beatriz; Norrie, John

2016-09-08

One in three women who have a prolapse operation will go on to have another operation, though not necessarily in the same compartment. Surgery can result in greater impairment of quality of life than the original prolapse itself (such as the development of new-onset urinary incontinence, or prolapse at a different site). Anterior and posterior prolapse surgery is most common (90 % of operations), but around 43 % of women also have a uterine (34 %) or vault (9 %) procedure at the same time. There is not enough evidence from randomised controlled trials (RCTs) to guide management of vault or uterine prolapse. The Vault or Uterine prolapse surgery Evaluation (VUE) study aims to assess the surgical management of upper compartment pelvic organ prolapse (POP) in terms of clinical effectiveness, cost-effectiveness and adverse events. VUE is two parallel, pragmatic, UK multicentre, RCTs (Uterine Trial and Vault Trial). Eligible for inclusion are women with vault or uterine prolapse: requiring a surgical procedure, suitable for randomisation and willing to be randomised. Randomisation will be computer-allocated separately for each trial, minimised on: requiring concomitant anterior and/or posterior POP surgery or not, concomitant incontinence surgery or not, age (under 60 years or 60 years and older) and surgeon. Participants will be randomly assigned, with equal probability to intervention or control arms in either the Uterine Trial or the Vault Trial. Uterine Trial participants will receive either a vaginal hysterectomy or a uterine preservation procedure. Vault Trial participants will receive either a vaginal sacrospinous fixation or an abdominal sacrocolpopexy. Participants will be followed up by postal questionnaires (6 months post surgery and 12 months post randomisation) and also reviewed in clinic 12 months post surgery. The primary outcome is the participant-reported Pelvic Organ Prolapse Symptom Score (POP-SS) at 12 months post randomisation. Demonstrating the efficacy of vault and uterine prolapse surgeries is relevant not only to patients and clinicians but also to health care providers, both in the UK and globally. Current controlled trials ISRCTN86784244 (assigned 19 October 2012), and the first subject was randomly assigned on 1 May 2013.

System and method for representing and manipulating three-dimensional objects on massively parallel architectures

DOEpatents

Karasick, Michael S.; Strip, David R.

1996-01-01

A parallel computing system is described that comprises a plurality of uniquely labeled, parallel processors, each processor capable of modelling a three-dimensional object that includes a plurality of vertices, faces and edges. The system comprises a front-end processor for issuing a modelling command to the parallel processors, relating to a three-dimensional object. Each parallel processor, in response to the command and through the use of its own unique label, creates a directed-edge (d-edge) data structure that uniquely relates an edge of the three-dimensional object to one face of the object. Each d-edge data structure at least includes vertex descriptions of the edge and a description of the one face. As a result, each processor, in response to the modelling command, operates upon a small component of the model and generates results, in parallel with all other processors, without the need for processor-to-processor intercommunication.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

PubMed

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: study protocol for a randomised controlled trial.

PubMed

Lyttle, Mark D; Gamble, Carrol; Messahel, Shrouk; Hickey, Helen; Iyer, Anand; Woolfall, Kerry; Humphreys, Amy; Bacon, Naomi E A; Roper, Louise; Babl, Franz E; Dalziel, Stuart R; Ryan, Mary; Appleton, Richard E

2017-06-19

Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE. This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up. This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting. ISRCTN identifier, ISRCTN22567894 . Registered on 27 August 2015 EudraCT identifier, 2014-002188-13 . Registered on 21 May 2014 NIHR HTA Grant: 12/127/134.

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

PubMed

Brown, Sarah; Smith, Isabelle L; Brown, Julia M; Hulme, Claire; McGinnis, Elizabeth; Stubbs, Nikki; Nelson, E Andrea; Muir, Delia; Rutherford, Claudia; Walker, Kay; Henderson, Valerie; Wilson, Lyn; Gilberts, Rachael; Collier, Howard; Fernandez, Catherine; Hartley, Suzanne; Bhogal, Moninder; Coleman, Susanne; Nixon, Jane E

2016-12-20

Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial

PubMed Central

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-01-01

Introduction Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Methods and analysis Inclusion criteria are patients 7–15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). Ethics and dissemination This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. Trial registration number ClinicalTrials.gov NCT02084433. PMID:26163031

Split-mouth and parallel-arm trials to compare pain with intraosseous anaesthesia delivered by the computerised Quicksleeper system and conventional infiltration anaesthesia in paediatric oral healthcare: protocol for a randomised controlled trial.

PubMed

Smaïl-Faugeron, Violaine; Muller-Bolla, Michèle; Sixou, Jean-Louis; Courson, Frédéric

2015-07-10

Local anaesthesia is commonly used in paediatric oral healthcare. Infiltration anaesthesia is the most frequently used, but recent developments in anaesthesia techniques have introduced an alternative: intraosseous anaesthesia. We propose to perform a split-mouth and parallel-arm multicentre randomised controlled trial (RCT) comparing the pain caused by the insertion of the needle for the injection of conventional infiltration anaesthesia, and intraosseous anaesthesia by the computerised QuickSleeper system, in children and adolescents. Inclusion criteria are patients 7-15 years old with at least 2 first permanent molars belonging to the same dental arch (for the split-mouth RCT) or with a first permanent molar (for the parallel-arm RCT) requiring conservative or endodontic treatment limited to pulpotomy. The setting of this study is the Department of Paediatric Dentistry at 3 University dental hospitals in France. The primary outcome measure will be pain reported by the patient on a visual analogue scale concerning the insertion of the needle and the injection/infiltration. Secondary outcomes are latency, need for additional anaesthesia during the treatment and pain felt during the treatment. We will use a computer-generated permuted-block randomisation sequence for allocation to anaesthesia groups. The random sequences will be stratified by centre (and by dental arch for the parallel-arm RCT). Only participants will be blinded to group assignment. Data will be analysed by the intent-to-treat principle. In all, 160 patients will be included (30 in the split-mouth RCT, 130 in the parallel-arm RCT). This protocol has been approved by the French ethics committee for the protection of people (Comité de Protection des Personnes, Ile de France I) and will be conducted in full accordance with accepted ethical principles. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. ClinicalTrials.gov NCT02084433. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Parallel consistent labeling algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samal, A.; Henderson, T.

Mackworth and Freuder have analyzed the time complexity of several constraint satisfaction algorithms. Mohr and Henderson have given new algorithms, AC-4 and PC-3, for arc and path consistency, respectively, and have shown that the arc consistency algorithm is optimal in time complexity and of the same order space complexity as the earlier algorithms. In this paper, they give parallel algorithms for solving node and arc consistency. They show that any parallel algorithm for enforcing arc consistency in the worst case must have O(na) sequential steps, where n is number of nodes, and a is the number of labels per node.more » They give several parallel algorithms to do arc consistency. It is also shown that they all have optimal time complexity. The results of running the parallel algorithms on a BBN Butterfly multiprocessor are also presented.« less

A comparison of two treatments for childhood apraxia of speech: methods and treatment protocol for a parallel group randomised control trial

PubMed Central

2012-01-01

Background Childhood Apraxia of Speech is an impairment of speech motor planning that manifests as difficulty producing the sounds (articulation) and melody (prosody) of speech. These difficulties may persist through life and are detrimental to academic, social, and vocational development. A number of published single subject and case series studies of speech treatments are available. There are currently no randomised control trials or other well designed group trials available to guide clinical practice. Methods/Design A parallel group, fixed size randomised control trial will be conducted in Sydney, Australia to determine the efficacy of two treatments for Childhood Apraxia of Speech: 1) Rapid Syllable Transition Treatment and the 2) Nuffield Dyspraxia Programme – Third edition. Eligible children will be English speaking, aged 4–12 years with a diagnosis of suspected CAS, normal or adjusted hearing and vision, and no comprehension difficulties or other developmental diagnoses. At least 20 children will be randomised to receive one of the two treatments in parallel. Treatments will be delivered by trained and supervised speech pathology clinicians using operationalised manuals. Treatment will be administered in 1-hour sessions, 4 times per week for 3 weeks. The primary outcomes are speech sound and prosodic accuracy on a customised 292 item probe and the Diagnostic Evaluation of Articulation and Phonology inconsistency subtest administered prior to treatment and 1 week, 1 month and 4 months post-treatment. All post assessments will be completed by blinded assessors. Our hypotheses are: 1) treatment effects at 1 week post will be similar for both treatments, 2) maintenance of treatment effects at 1 and 4 months post will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment, and 3) generalisation of treatment effects to untrained related speech behaviours will be greater for Rapid Syllable Transition Treatment than Nuffield Dyspraxia Programme treatment. This protocol was approved by the Human Research Ethics Committee, University of Sydney (#12924). Discussion This will be the first randomised control trial to test treatment for CAS. It will be valuable for clinical decision-making and providing evidence-based services for children with CAS. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12612000744853 PMID:22863021

Migraine with prolonged aura: phenotype and treatment.

PubMed

Viana, Michele; Afridi, Shazia

2018-01-01

We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

GPU-Based Point Cloud Superpositioning for Structural Comparisons of Protein Binding Sites.

PubMed

Leinweber, Matthias; Fober, Thomas; Freisleben, Bernd

2018-01-01

In this paper, we present a novel approach to solve the labeled point cloud superpositioning problem for performing structural comparisons of protein binding sites. The solution is based on a parallel evolution strategy that operates on large populations and runs on GPU hardware. The proposed evolution strategy reduces the likelihood of getting stuck in a local optimum of the multimodal real-valued optimization problem represented by labeled point cloud superpositioning. The performance of the GPU-based parallel evolution strategy is compared to a previously proposed CPU-based sequential approach for labeled point cloud superpositioning, indicating that the GPU-based parallel evolution strategy leads to qualitatively better results and significantly shorter runtimes, with speed improvements of up to a factor of 1,500 for large populations. Binary classification tests based on the ATP, NADH, and FAD protein subsets of CavBase, a database containing putative binding sites, show average classification rate improvements from about 92 percent (CPU) to 96 percent (GPU). Further experiments indicate that the proposed GPU-based labeled point cloud superpositioning approach can be superior to traditional protein comparison approaches based on sequence alignments.

Food label education does not reduce sodium intake in people with type 2 diabetes mellitus. A randomised controlled trial.

PubMed

Petersen, Kristina S; Torpy, David J; Chapman, Ian M; Guha, Sanghamitra; Clifton, Peter M; Turner, Kirsty; Keogh, Jennifer B

2013-09-01

Sodium intake is high in people with type 2 diabetes (T2DM). The aim of this study was to investigate whether urinary sodium excretion can be reduced by educating people with T2DM to read food labels and choose low sodium products. In a 3 month randomised controlled trial, 78 men (n=49) and women (n=29) with T2DM were recruited from a Diabetes Centre at a University teaching hospital. The intervention group was educated in a single session to use the nutrition information panel on food labels to choose products which complied with the Food Standards Australia New Zealand (FSANZ) guideline of <120 mg sodium/100 g food. The control group continued on their usual diet. The primary outcome measure was 24h urinary sodium excretion which was performed at baseline and 3 months. Data was analysed using repeated measures analysis of variance, independent samples t-test and Pearson's correlations. At 3 months mean urinary sodium excretion was unchanged in the intervention (174±13 mmol/24 h and 175±13 mmol/24 h) and control group (167±15mmol/24h and 161±13 mmol/24 h), and there was no between group difference (p>0.05). Sodium excretion was not reduced following the label reading education provided to this group of people with T2DM. Copyright © 2013 Elsevier Ltd. All rights reserved.

A simple procedure for parallel sequence analysis of both strands of 5'-labeled DNA.

PubMed

Razvi, F; Gargiulo, G; Worcel, A

1983-08-01

Ligation of a 5'-labeled DNA restriction fragment results in a circular DNA molecule carrying the two 32Ps at the reformed restriction site. Double digestions of the circular DNA with the original enzyme and a second restriction enzyme cleavage near the labeled site allows direct chemical sequencing of one 5'-labeled DNA strand. Similar double digestions, using an isoschizomer that cleaves differently at the 32P-labeled site, allows direct sequencing of the now 3'-labeled complementary DNA strand. It is possible to directly sequence both strands of cloned DNA inserts by using the above protocol and a multiple cloning site vector that provides the necessary restriction sites. The simultaneous and parallel visualization of both DNA strands eliminates sequence ambiguities. In addition, the labeled circular molecules are particularly useful for single-hit DNA cleavage studies and DNA footprint analysis. As an example, we show here an analysis of the micrococcal nuclease-induced breaks on the two strands of the somatic 5S RNA gene of Xenopus borealis, which suggests that the enzyme may recognize and cleave small AT-containing palindromes along the DNA helix.

System and method for representing and manipulating three-dimensional objects on massively parallel architectures

DOEpatents

Karasick, M.S.; Strip, D.R.

1996-01-30

A parallel computing system is described that comprises a plurality of uniquely labeled, parallel processors, each processor capable of modeling a three-dimensional object that includes a plurality of vertices, faces and edges. The system comprises a front-end processor for issuing a modeling command to the parallel processors, relating to a three-dimensional object. Each parallel processor, in response to the command and through the use of its own unique label, creates a directed-edge (d-edge) data structure that uniquely relates an edge of the three-dimensional object to one face of the object. Each d-edge data structure at least includes vertex descriptions of the edge and a description of the one face. As a result, each processor, in response to the modeling command, operates upon a small component of the model and generates results, in parallel with all other processors, without the need for processor-to-processor intercommunication. 8 figs.

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

PubMed Central

Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R.; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B.; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

2017-01-01

Objectives To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. Methods and findings We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Conclusion Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found. PMID:28617801

Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial

PubMed Central

Baselga, José; Bradbury, Ian; Eidtmann, Holger; Di Cosimo, Serena; de Azambuja, Evandro; Aura, Claudia; Gómez, Henry; Dinh, Phuong; Fauria, Karine; Van Dooren, Veerle; Aktan, Gursel; Goldhirsch, Aron; Chang, Tsai-Wang; Horváth, Zsolt; Coccia-Portugal, Maria; Domont, Julien; Tseng, Ling-Min; Kunz, Georg; Sohn, Joo Hyuk; Semiglazov, Vladimir; Lerzo, Guillermo; Palacova, Marketa; Probachai, Volodymyr; Pusztai, Lajos; Untch, Michael; Gelber, Richard D; Piccart-Gebhart, Martine

2017-01-01

Summary Background The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. Methods In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/kg, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m2) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00553358. Findings 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1–59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4–37·5]; difference 21·1%, 9·1–34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1–32·3]) and the trastuzumab (difference −4·8%, −17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%]). Interpretation Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting. Funding GlaxoSmithKline. PMID:22257673

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting

PubMed Central

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-01-01

Introduction Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Methods and analysis Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3–4 physiotherapists) and a focus group (n=6–8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). Ethics and dissemination This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). Trial registration number ISRCTN84528320. PMID:27412105

Acute Whiplash Injury Study (AWIS): a protocol for a cluster randomised pilot and feasibility trial of an Active Behavioural Physiotherapy Intervention in an insurance private setting.

PubMed

Wiangkham, Taweewat; Duda, Joan; Haque, M Sayeed; Price, Jonathan; Rushton, Alison

2016-07-13

Whiplash-associated disorder (WAD) causes substantial social and economic burden internationally. Up to 60% of patients with WAD progress to chronicity. Research therefore needs to focus on effective management in the acute stage to prevent the development of chronicity. Approximately 93% of patients are classified as WADII (neck complaint and musculoskeletal sign(s)), and in the UK, most are managed in the private sector. In our recent systematic review, a combination of active and behavioural physiotherapy was identified as potentially effective in the acute stage. An Active Behavioural Physiotherapy Intervention (ABPI) was developed through combining empirical (modified Delphi study) and theoretical (social cognitive theory focusing on self-efficacy) evidence. This pilot and feasibility trial has been designed to inform the design of an adequately powered definitive randomised controlled trial. Two parallel phases. (1) An external pilot and feasibility cluster randomised double-blind (assessor and participants), parallel two-arm (ABPI vs standard physiotherapy) clinical trial to evaluate procedures and feasibility. Six UK private physiotherapy clinics will be recruited and cluster randomised by a computer-generated randomisation sequence. Sixty participants (30 each arm) will be assessed at recruitment (baseline) and at 3 months postbaseline. The planned primary outcome measure is the neck disability index. (2) An embedded exploratory qualitative study using semistructured indepth interviews (n=3-4 physiotherapists) and a focus group (n=6-8 patients) and entailing the recruitment of purposive samples will explore perceptions of the ABPI. Quantitative data will be analysed descriptively. Qualitative data will be coded and analysed deductively (identify themes) and inductively (identify additional themes). This trial is approved by the University of Birmingham Ethics Committee (ERN_15-0542). ISRCTN84528320. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures.

PubMed

Donati, Filippo; Gobbi, Giuseppe; Campistol, Jaume; Rapatz, Guenter; Daehler, Maja; Sturm, Yvonne; Aldenkamp, Albert P

2007-12-01

To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to <17 years) with newly diagnosed partial seizures. A multicentre, open-label, randomised, active-control, three-arm, parallel-group, 6-month study. The primary cognitive variable, the Computerized Visual Searching Task (CVST), assessed mental information processing speed and attention. Secondary variables included additional tests assessing psychomotor speed, alertness, memory and learning, and non-verbal intelligence. Of 112 patients randomised, 99 completed the study. The dropout rate was 11.6%; 13 patients discontinued due to adverse events (n=5) or unsatisfactory therapeutic effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

Single application of 4% dimeticone liquid gel versus two applications of 1% permethrin creme rinse for treatment of head louse infestation: a randomised controlled trial

PubMed Central

2013-01-01

Background A previous study indicated that a single application of 4% dimeticone liquid gel was effective in treating head louse infestation. This study was designed to confirm this in comparison with two applications of 1% permethrin. Methods We have performed a single centre parallel group, randomised, controlled, open label, community based trial, with domiciliary visits, in Cambridgeshire, UK. Treatments were allocated through sealed instructions derived from a computer generated list. We enrolled 90 children and adults with confirmed head louse infestation analysed by intention to treat (80 per-protocol after 4 drop outs and 6 non-compliant). The comparison was between 4% dimeticone liquid gel applied once for 15 minutes and 1% permethrin creme rinse applied for 10 minutes, repeated after 7 days as per manufacturer’s directions. Evaluated by elimination of louse infestation after completion of treatment application regimen. Results Intention to treat comparison of a single dimeticone liquid gel treatment with two of permethrin gave success for 30/43 (69.8%) of the dimeticone liquid gel group and 7/47 (14.9%) of the permethrin creme rinse group (OR 13.19, 95% CI 4.69 to 37.07) (p < 0.001). Per protocol results were similar with 27/35 (77.1%) success for dimeticone versus 7/45 (15.6%) for permethrin. Analyses by household gave essentially similar outcomes. Conclusions The study showed one 15 minute application of 4% dimeticone liquid gel was superior to two applications of 1% permethrin creme rinse (p < 0.001). The low efficacy of permethrin suggests it should be withdrawn. Trial registration Current Controlled Trials ISRCTN88144046. PMID:23548062

A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department.

PubMed

Ong, Marcus Eng Hock; Tiah, Ling; Leong, Benjamin Sieu-Hon; Tan, Elaine Ching Ching; Ong, Victor Yeok Kein; Tan, Elizabeth Ai Theng; Poh, Bee Yen; Pek, Pin Pin; Chen, Yuming

2012-08-01

To compare vasopressin and adrenaline in the treatment of patients with cardiac arrest presenting to or in the Emergency Department (ED). A randomised, double-blind, multi-centre, parallel-design clinical trial in four adult hospitals. Eligible cardiac arrest patients (confirmed by the absence of pulse, unresponsiveness and apnea) aged >16 (aged>21 for one hospital) were randomly assigned to intravenous adrenaline (1mg) or vasopressin (40 IU) at ED. Patients with traumatic cardiac arrest or contraindication for cardiopulmonary resuscitation (CPR) were excluded. Patients received additional open label doses of adrenaline as per current guidelines. Primary outcome was survival to hospital discharge (defined as participant discharged alive or survival to 30 days post-arrest). The study recruited 727 participants (adrenaline = 353; vasopressin = 374). Baseline characteristics of the two groups were comparable. Eight participants (2.3%) from adrenaline and 11 (2.9%) from vasopressin group survived to hospital discharge with no significant difference between groups (p = 0.27, RR = 1.72, 95% CI = 0.65-4.51). After adjustment for race, medical history, bystander CPR and prior adrenaline given, more participants survived to hospital admission with vasopressin (22.2%) than with adrenaline (16.7%) (p = 0.05, RR = 1.43, 95% CI = 1.02-2.04). Sub-group analysis suggested improved outcomes for vasopressin in participants with prolonged arrest times. Combination of vasopressin and adrenaline did not improve long term survival but seemed to improve survival to admission in patients with prolonged cardiac arrest. Further studies on the effect of vasopressin combined with therapeutic hypothermia on patients with prolonged cardiac arrest are needed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial.

PubMed

Azzopardi, Denis; Robertson, Nicola J; Bainbridge, Alan; Cady, Ernest; Charles-Edwards, Geoffrey; Deierl, Aniko; Fagiolo, Gianlorenzo; Franks, Nicholas P; Griffiths, James; Hajnal, Joseph; Juszczak, Edmund; Kapetanakis, Basil; Linsell, Louise; Maze, Mervyn; Omar, Omar; Strohm, Brenda; Tusor, Nora; Edwards, A David

2016-02-01

Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. UK Medical Research Council. Copyright © 2016 Azzopardi et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study).

PubMed

Marwood, L; Taylor, R; Goldsmith, K; Romeo, R; Holland, R; Pickles, A; Hutchinson, J; Dietch, D; Cipriani, A; Nair, R; Attenburrow, M-J; Young, A H; Geddes, J; McAllister-Williams, R H; Cleare, A J

2017-06-26

Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group. The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects. The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies. ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.

Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

PubMed Central

Rauniyar, Navin

2015-01-01

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. PMID:26633379

Xray: N-dimensional, labeled arrays for analyzing physical datasets in Python

NASA Astrophysics Data System (ADS)

Hoyer, S.

2015-12-01

Efficient analysis of geophysical datasets requires tools that both preserve and utilize metadata, and that transparently scale to process large datas. Xray is such a tool, in the form of an open source Python library for analyzing the labeled, multi-dimensional array (tensor) datasets that are ubiquitous in the Earth sciences. Xray's approach pairs Python data structures based on the data model of the netCDF file format with the proven design and user interface of pandas, the popular Python data analysis library for labeled tabular data. On top of the NumPy array, xray adds labeled dimensions (e.g., "time") and coordinate values (e.g., "2015-04-10"), which it uses to enable a host of operations powered by these labels: selection, aggregation, alignment, broadcasting, split-apply-combine, interoperability with pandas and serialization to netCDF/HDF5. Many of these operations are enabled by xray's tight integration with pandas. Finally, to allow for easy parallelism and to enable its labeled data operations to scale to datasets that does not fit into memory, xray integrates with the parallel processing library dask.

DNA with Parallel Strand Orientation: A Nanometer Distance Study with Spin Labels in the Watson-Crick and the Reverse Watson-Crick Double Helix.

PubMed

Wunnicke, Dorith; Ding, Ping; Yang, Haozhe; Seela, Frank; Steinhoff, Heinz-Jürgen

2015-10-29

Parallel-stranded (ps) DNA characterized by its sugar-phosphate backbones pointing in the same direction represents an alternative pairing system to antiparallel-stranded (aps) DNA with the potential to inhibit transcription and translation. 25-mer oligonucleotides were selected containing only dA·dT base pairs to compare spin-labeled nucleobase distances over a range of 10 or 15 base pairs in ps DNA with those in aps DNA. By means of the copper(I)-catalyzed Huisgen-Meldal-Sharpless alkyne-azide cycloaddition, the spin label 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl was clicked to 7-ethynyl-7-deaza-2'-deoxyadenosine or 5-ethynyl-2'-deoxyuridine to yield 25-mer oligonucleotides incorporating two spin labels. The interspin distances between spin labeled residues were determined by pulse EPR spectroscopy. The results reveal that in ps DNA these distances are between 5 and 10% longer than in aps DNA when the labeled DNA segment is located near the center of the double helix. The interspin distance in ps DNA becomes shorter compared with aps DNA when one of the spin labels occupies a position near the end of the double helix.

Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

PubMed Central

Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

2013-01-01

Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

Growth and change in blood haemoglobin concentration among underweight Malawian infants receiving fortified spreads for 12 weeks: a preliminary trial

USDA-ARS?s Scientific Manuscript database

Fortified spreads (FSs) have proven effective in the rehabilitation of severely malnourished children. We examined acceptability, growth and change in blood haemoglobin (Hb) concentration among moderately underweight ambulatory infants given FS. This was a randomised, controlled, parallel-group, inv...

The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

PubMed

Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

2016-12-07

It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.

PubMed

Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. International Standard Randomised Controlled Trials Number: ISRCTN63579542 , 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379 , 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.

The effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial.

PubMed

Kuyken, Willem; Nuthall, Elizabeth; Byford, Sarah; Crane, Catherine; Dalgleish, Tim; Ford, Tamsin; Greenberg, Mark T; Ukoumunne, Obioha C; Viner, Russell M; Williams, J Mark G

2017-04-26

Mindfulness-based approaches for adults are effective at enhancing mental health, but few controlled trials have evaluated their effectiveness or cost-effectiveness for young people. The primary aim of this trial is to evaluate the effectiveness and cost-effectiveness of a mindfulness training (MT) programme to enhance mental health, wellbeing and social-emotional behavioural functioning in adolescence. To address this aim, the design will be a superiority, cluster randomised controlled, parallel-group trial in which schools offering social and emotional provision in line with good practice (Formby et al., Personal, Social, Health and Economic (PSHE) Education: A mapping study of the prevalent models of delivery and their effectiveness, 2010; OFSTED, Not Yet Good Enough: Personal, Social, Health and Economic Education in schools, 2013) will be randomised to either continue this provision (control) or include MT in this provision (intervention). The study will recruit and randomise 76 schools (clusters) and 5700 school students aged 12 to 14 years, followed up for 2 years. The study will contribute to establishing if MT is an effective and cost-effective approach to promoting mental health in adolescence. International Standard Randomised Controlled Trials, identifier: ISRCTN86619085 . Registered on 3 June 2016.

Long-term effect of smartphone-delivered Interval Walking Training on physical activity in patients with type 2 diabetes: protocol for a parallel group single-blinded randomised controlled trial

PubMed Central

Ried-Larsen, Mathias; Karstoft, Kristian; Brinkløv, Cecilie Fau; Brøns, Charlotte; Nielsen, Rasmus Oestergaard; Nielsen, Jens Steen; Vaag, Allan Arthur; Pedersen, Bente Klarlund; Langberg, Henning

2017-01-01

Introduction Physical activity is a cornerstone in type 2 diabetes (T2D) rehabilitation. Effective long-term and low-cost strategies to keep these patients' physically active are needed. However, maintaining physical activity behaviour is difficult once formalised interventions end. Structured exercise training supported by mobile technology and remote feedback is potentially an effective strategy. The objective of the trial is to investigate whether mobile health support using the InterWalk application for smartphones is effective in increasing physical activity levels in persons with T2D over time compared with standard care. We investigate whether Interval Walking Training using the InterWalk application is superior to Danish municipality-based rehabilitation in increasing moderate-and-vigorous physical activity levels in patients with T2D across 52 weeks. Secondary, we hypothesise that a motivational programme added from end of intervention to 52 weeks further increases level of physical activity in everyday life in patients with T2D. Methods and analysis The trial is a parallel-group, open-labelled, randomised controlled trial with long-term follow-up at 52 week including patients with T2D. The primary outcome is change in moderate-and-vigorous physical activity. The key secondary outcome includes motivation for physical activity behaviour change. Other secondary outcomes are VO2-peak, strength in the lower extremities. Exclusion criterion is medical contraindication to exercise. We include up to 246 patients and randomly allocate them into a control (standard group) or an experimental group (8–12 weeks of IWT supported by the smartphone-based InterWalk application) in a 1:2 fashion. After intervention, the experimental group is randomly allocated into two follow-up conditions with unsupervised IWT with or without motivational support until 52-week follow-up. The intention-to-treat principle is applied. Ethics and dissemination The local regional Research Ethics Committee in Denmark (H-1-2014-074) and the Danish Data Protection Agency (j.nr. 2014-54-0897) have approved the trial. Positive, negative or inconclusive results will be disseminated in scientific journals and conferences. Trial registration number NCT02341690. PMID:28389489

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.

PubMed

Brown, Sarah; Hinsley, Samantha; Ballesteros, Mónica; Bourne, Sue; McGarry, Paul; Sherratt, Debbie; Flanagan, Louise; Gregory, Walter; Cavenagh, Jamie; Owen, Roger; Williams, Cathy; Kaiser, Martin; Low, Eric; Yong, Kwee

2016-01-01

Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. The trial is registered under ISRCTN17354232, December 2012.

Apparatus for reading two-dimensional electrophoretograms containing. beta. -ray-emitting labeled compounds

DOEpatents

Anderson, H.L.; Kinnison, W.W.; Lillberg, J.W.

1985-04-30

An apparatus and method for electronically reading planar two-dimensional ..beta..-ray emitter-labeled gel electrophoretograms. A single, flat rectangular multiwire proportional chamber is placed in close proximity to the gel and the assembly placed in an intense uniform magnetic field disposed in a perpendicular manner to the rectangular face of the proportional chamber. Beta rays emitted in the direction of the proportional chamber are caused to execute helical motions which substantially preserve knowledge the coordinates of their origin in the gel. Perpendicularly oriented, parallel wire, parallel plane cathodes electronically sense the location of the ..beta..-rays from ionization generated thereby in a detection gas coupled with an electron avalanche effect resulting from the action of a parallel wire anode located therebetween. A scintillator permits the present apparatus to be rendered insensitive when signals are generated from cosmic rays incident on the proportional chamber. Resolution for concentrations of radioactive compounds in the gel exceeds 700-..mu..m. The apparatus and method of the present invention represent a significant improvement over conventional autoradiographic techniques in dynamic range, linearity and sensitivity of data collection. A concentration and position map for gel electrophoretograms having significant concentrations of labeled compounds and/or highly radioactive labeling nuclides can generally be obtained in less than one hour.

Apparatus and method for reading two-dimensional electrophoretograms containing .beta.-ray-emitting labeled compounds

DOEpatents

Anderson, Herbert L.; Kinnison, W. Wayne; Lillberg, John W.

1987-01-01

Apparatus and method for electronically reading planar two dimensional .beta.-ray emitter-labeled gel electrophoretograms. A single, flat rectangular multiwire proportional chamber is placed in close proximity to the gel and the assembly placed in an intense uniform magnetic field disposed in a perpendicular manner to the rectangular face of the proportional chamber. Beta rays emitted in the direction of the proportional chamber are caused to execute helical motions which substantially preserve knowledge of the coordinates of their origin in the gel. Perpendicularly oriented, parallel wire, parallel plane cathodes electronically sense the location of the .beta.-rays from ionization generated thereby in a detection gas coupled with an electron avalanche effect resulting from the action of a parallel wire anode located therebetween. A scintillator permits the present apparatus to be rendered insensitive when signals are generated from cosmic rays incident on the proportional chamber. Resolution for concentrations of radioactive compounds in the gel exceeds 700 .mu.m. The apparatus and method of the present invention represent a significant improvement over conventional autoradiographic techniques in dynamic range, linearity and sensitivity of data collection. A concentration and position map for gel electrophoretograms having significant concentrations of labeled compounds and/or highly radioactive labeling nuclides can generally be obtained in less than one hour.

Using Environmental Print to Enhance Emergent Literacy and Print Motivation

ERIC Educational Resources Information Center

Neumann, Michelle M.; Hood, Michelle; Ford, Ruth M.

2013-01-01

Given the ubiquitous and salient nature of environmental print, it has the potential to scaffold emergent literacy in young children. This randomised control study evaluated the effects of using environmental print compared to standard print (the same labels in manuscript form) in an 8-week intervention (30 min per week) to foster 3- to…

Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study.

PubMed

Schmidt, C; Ahmad, T; Tulassay, Z; Baumgart, D C; Bokemeyer, B; Howaldt, S; Stallmach, A; Büning, C

2016-08-01

Ferric maltol was effective and well-tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12-week placebo-controlled trial. To perform a Phase 3 extension study evaluating long-term efficacy and safety with ferric maltol in inflammatory bowel disease patients in whom oral ferrous therapies had failed to correct iron deficiency anaemia. After 12 weeks of randomised, double-blind treatment, patients with iron deficiency anaemia and mild-to-moderate ulcerative colitis or Crohn's disease received open-label ferric maltol 30 mg b.d. for 52 weeks. 111 patients completed randomised treatment and 97 entered the open-label ferric maltol extension. In patients randomised to ferric maltol ('continued'; n = 50), mean ± s.d. haemoglobin increased by 3.07 ± 1.46 g/dL between baseline and Week 64. In patients randomised to placebo ('switch'; n = 47), haemoglobin increased by 2.19 ± 1.61 g/dL. Normal haemoglobin was achieved in high proportions of both continued and switch patients (89% and 83% at Week 64, respectively). Serum ferritin increased from 8.9 μg/L (baseline) to 26.0 μg/L (Week 12) in ferric maltol-treated patients, and to 57.4 μg/L amongst all patients at Week 64. In total, 80% of patients reported ≥1 adverse event by Week 64. Adverse events considered related to ferric maltol were recorded in 27/111 (24%) patients: 8/18 discontinuations due to adverse events were treatment-related. One patient was withdrawn due to increased ulcerative colitis activity. Normal haemoglobin was observed in ≥80% of patients from weeks 20-64 of long-term ferric maltol treatment, with concomitant increases in iron storage parameters. Ferric maltol was well-tolerated throughout this 64-week study. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

PubMed

Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

2017-09-01

For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit was observed by the investigators (eg, an improvement in cognition or intracranial pressure). The primary endpoint was intracranial progression-free survival (PFS), defined as the time from randomisation to either intracranial disease progression or death from any cause. We assessed efficacy and safety in the intention-to-treat population (all participants who received at least one dose of study treatment), hypothesising that intracranial PFS would be 40% longer (hazard ratio [HR] 0·60) with icotinib compared with WBI. This trial is registered with ClinicalTrials.gov, number NCT01724801. Between Dec 10, 2012, and June 30, 2015, we assigned 176 participants to treatment: 85 to icotinib and 91 to WBI. 18 withdrew from the WBI group before treatment, leaving 73 for assessment. Median follow-up was 16·5 months (IQR 11·5-21·5). Median intracranial PFS was 10·0 months (95% CI 5·6-14·4) with icotinib versus 4·8 months (2·4-7·2) with WBI (equating to a 44% risk reduction with icotinib for an event of intracranial disease progression or death; HR 0·56, 95% CI 0·36-0·90; p=0·014). Adverse events of grade 3 or worse were reported in seven (8%) of 85 patients in the icotinib group and 28 (38%) of 73 patients in the WBI group. Raised concentrations of alanine aminotransferase and rash were the most common adverse events of any grade in both groups, occurring in around 20-30% of each group. At the time of final analysis, 42 (49%) patients in the icotinib group and 37 (51%) in the WBI group had died. 78 of these patients died from disease progression, and one patient in the WBI group died from thrombogenesis related to chemotherapy. In patients with EGFR-mutant NSCLC and multiple brain metastases, icotinib was associated with significantly longer intracranial PFS than WBI plus chemotherapy, indicating that icotinib might be a better first-line therapeutic option for this patient population. Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine, National Health and Family Planning Commission of China, Guangzhou Science and Technology Bureau, Betta Pharmaceuticals, and the Chinese Thoracic Oncology Group. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health trainer-led motivational intervention plus usual care for people under community supervision compared with usual care alone: a study protocol for a parallel-group pilot randomised controlled trial (STRENGTHEN)

PubMed Central

Thompson, Tom P; Callaghan, Lynne; Hazeldine, Emma; Quinn, Cath; Walker, Samantha; Byng, Richard; Wallace, Gary; Creanor, Siobhan; Green, Colin; Hawton, Annie; Annison, Jill; Sinclair, Julia; Senior, Jane; Taylor, Adrian H

2018-01-01

Introduction People with experience of the criminal justice system typically have worse physical and mental health, lower levels of mental well-being and have less healthy lifestyles than the general population. Health trainers have worked with offenders in the community to provide support for lifestyle change, enhance mental well-being and signpost to appropriate services. There has been no rigorous evaluation of the effectiveness and cost-effectiveness of providing such community support. This study aims to determine the feasibility and acceptability of conducting a randomised trial and delivering a health trainer intervention to people receiving community supervision in the UK. Methods and analysis A multicentre, parallel, two-group randomised controlled trial recruiting 120 participants with 1:1 individual allocation to receive support from a health trainer and usual care or usual care alone, with mixed methods process evaluation. Participants receive community supervision from an offender manager in either a Community Rehabilitation Company or the National Probation Service. If they have served a custodial sentence, then they have to have been released for at least 2 months. The supervision period must have at least 7 months left at recruitment. Participants are interested in receiving support to change diet, physical activity, alcohol use and smoking and/or improve mental well-being. The primary outcome is mental well-being with secondary outcomes related to smoking, physical activity, alcohol consumption and diet. The primary outcome will inform sample size calculations for a definitive trial. Ethics and dissemination The study has been approved by the Health and Care Research Wales Ethics Committee (REC reference 16/WA/0171). Dissemination will include publication of the intervention development process and findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals. Results will also be disseminated to stakeholders and trial participants. Trial registration numbers ISRCTN80475744; Pre-results. PMID:29866736

Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trial.

PubMed

Zaman, Khalequ; Estívariz, Concepción F; Morales, Michelle; Yunus, Mohammad; Snider, Cynthia J; Gary, Howard E; Weldon, William C; Oberste, M Steven; Wassilak, Steven G; Pallansch, Mark A; Anand, Abhijeet

2018-06-01

Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 10 5 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual. Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181 in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non-inferior to 4 week intervals because the lower bound of the absolute differences in the percentage of immune responses were greater than -10% (-4·2% [90% CI -7·9 to -0·4] in the 1 week group and -1·8% [-5·0 to 1·5] in the 2 week group vs the 4 week group). The immune response elicited by two mOPV2 doses 4 weeks apart was not different when IPV was added to the first dose (176 [97%] of 182 infants with IPV vs 176 [97%] of 181 without IPV; p=1·0). During the trial, two serious adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events were not attributed to the vaccines. Administration of mOPV2 at short intervals does not interfere with its immunogenicity. The addition of IPV to the first mOPV2 dose did not improve poliovirus type 2 immune response. US Centers for Disease Control and Prevention. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effectiveness of a Guided Self-help Manual in Strengthening Resilience in People Diagnosed with Moderate Depression and Their Family Caregivers in Thailand: A Randomised Controlled Trial.

PubMed

McCann, Terence V; Songprakun, Wallapa; Stephenson, John

2017-08-01

The growing incidence of depression in developing countries, such as Thailand, is placing increasing pressure on public mental health services, and those living in rural areas have limited access to these services. Resilience is integral to the recovery of people with depression and to caregivers. This parallel-group randomised controlled trial evaluated the effectiveness of a guided self-help manual in improving resilience in adults diagnosed with moderate depression and their primary caregivers in Thailand. Our findings provide preliminary evidence that the approach is an effective way of increasing resilience in adults with depression and their caregivers.

Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial.

PubMed

Dungan, Kathleen M; Povedano, Santiago Tofé; Forst, Thomas; González, José G González; Atisso, Charles; Sealls, Whitney; Fahrbach, Jessie L

2014-10-11

Dulaglutide and liraglutide, both glucagon-like peptide-1 (GLP-1) receptor agonists, improve glycaemic control and reduce weight in patients with type 2 diabetes. In a head-to-head trial, we compared the safety and efficacy of once-weekly dulaglutide with that of once-daily liraglutide in metformin-treated patients with uncontrolled type 2 diabetes. We did a phase 3, randomised, open-label, parallel-group study at 62 sites in nine countries between June 20, 2012, and Nov 25, 2013. Patients with inadequately controlled type 2 diabetes receiving metformin (≥1500 mg/day), aged 18 years or older, with glycated haemoglobin (HbA1c) 7·0% or greater (≥53 mmol/mol) and 10·0% or lower (≤86 mmol/mol), and body-mass index 45 kg/m(2) or lower were randomly assigned to receive once-weekly dulaglutide (1·5 mg) or once-daily liraglutide (1·8 mg). Randomisation was done according to a computer-generated random sequence with an interactive voice response system. Participants and investigators were not masked to treatment allocation. The primary outcome was non-inferiority (margin 0·4%) of dulaglutide compared with liraglutide for change in HbA1c (least-squares mean change from baseline) at 26 weeks. Safety data were collected for a further 4 weeks' follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01624259. We randomly assigned 599 patients to receive once-weekly dulaglutide (299 patients) or once-daily liraglutide (300 patients). 269 participants in each group completed treatment at week 26. Least-squares mean reduction in HbA1c was -1·42% (SE 0·05) in the dulaglutide group and -1·36% (0·05) in the liraglutide group. Mean treatment difference in HbA1c was -0·06% (95% CI -0·19 to 0·07, pnon-inferiority<0·0001) between the two groups. The most common gastrointestinal adverse events were nausea (61 [20%] in dulaglutide group vs 54 [18%] in liraglutide group), diarrhoea (36 [12%] vs 36 [12%]), dyspepsia (24 [8%] vs 18 [6%]), and vomiting (21 [7%] vs 25 [8%]), with similar rates of study or study drug discontinuation because of adverse events between the two groups (18 [6%] in each group). The hypoglycaemia rate was 0·34 (SE 1·44) and 0·52 (3·01) events per patient per year, respectively, and no severe hypoglycaemia was reported. Once-weekly dulaglutide is non-inferior to once-daily liraglutide for least-squares mean reduction in HbA1c, with a similar safety and tolerability profile. Eli Lilly and Company. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial.

PubMed

Woodcock, Ashley; Vestbo, Jørgen; Bakerly, Nawar Diar; New, John; Gibson, J Martin; McCorkindale, Sheila; Jones, Rupert; Collier, Susan; Lay-Flurrie, James; Frith, Lucy; Jacques, Loretta; Fletcher, Joanne L; Harvey, Catherine; Svedsater, Henrik; Leather, David

2017-11-18

Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice. We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 μg or 200 μg fluticasone furoate with 25 μg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198. Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70-2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3-2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups. In patients with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care. GlaxoSmithKline. Copyright © 2017 Elsevier Ltd. All rights reserved.

High sensitivity and high Q-factor nanoslotted parallel quadrabeam photonic crystal cavity for real-time and label-free sensing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Daquan; State Key Laboratory of Information Photonics and Optical Communications, School of Information and Communication Engineering, Beijing University of Posts and Telecommunications, Beijing 100876; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138

We experimentally demonstrate a label-free sensor based on nanoslotted parallel quadrabeam photonic crystal cavity (NPQC). The NPQC possesses both high sensitivity and high Q-factor. We achieved sensitivity (S) of 451 nm/refractive index unit and Q-factor >7000 in water at telecom wavelength range, featuring a sensor figure of merit >2000, an order of magnitude improvement over the previous photonic crystal sensors. In addition, we measured the streptavidin-biotin binding affinity and detected 10 ag/mL concentrated streptavidin in the phosphate buffered saline solution.

Automatic ground control point recognition with parallel associative memory

NASA Technical Reports Server (NTRS)

Al-Tahir, Raid; Toth, Charles K.; Schenck, Anton F.

1990-01-01

The basic principle of the associative memory is to match the unknown input pattern against a stored training set, and responding with the 'closest match' and the corresponding label. Generally, an associative memory system requires two preparatory steps: selecting attributes of the pattern class, and training the system by associating patterns with labels. Experimental results gained from using Parallel Associative Memory are presented. The primary concern is an automatic search for ground control points in aerial photographs. Synthetic patterns are tested followed by real data. The results are encouraging as a relatively high level of correct matches is reached.

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

OpenCL based machine learning labeling of biomedical datasets

NASA Astrophysics Data System (ADS)

Amoros, Oscar; Escalera, Sergio; Puig, Anna

2011-03-01

In this paper, we propose a two-stage labeling method of large biomedical datasets through a parallel approach in a single GPU. Diagnostic methods, structures volume measurements, and visualization systems are of major importance for surgery planning, intra-operative imaging and image-guided surgery. In all cases, to provide an automatic and interactive method to label or to tag different structures contained into input data becomes imperative. Several approaches to label or segment biomedical datasets has been proposed to discriminate different anatomical structures in an output tagged dataset. Among existing methods, supervised learning methods for segmentation have been devised to easily analyze biomedical datasets by a non-expert user. However, they still have some problems concerning practical application, such as slow learning and testing speeds. In addition, recent technological developments have led to widespread availability of multi-core CPUs and GPUs, as well as new software languages, such as NVIDIA's CUDA and OpenCL, allowing to apply parallel programming paradigms in conventional personal computers. Adaboost classifier is one of the most widely applied methods for labeling in the Machine Learning community. In a first stage, Adaboost trains a binary classifier from a set of pre-labeled samples described by a set of features. This binary classifier is defined as a weighted combination of weak classifiers. Each weak classifier is a simple decision function estimated on a single feature value. Then, at the testing stage, each weak classifier is independently applied on the features of a set of unlabeled samples. In this work, we propose an alternative representation of the Adaboost binary classifier. We use this proposed representation to define a new GPU-based parallelized Adaboost testing stage using OpenCL. We provide numerical experiments based on large available data sets and we compare our results to CPU-based strategies in terms of time and labeling speeds.

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial

PubMed Central

Wileman, Samantha M; Ramsay, Craig R; Mowat, N Ashley; Krukowski, Zygmunt H; Heading, Robert C; Thursz, Mark R; Campbell, Marion K

2008-01-01

Objective To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Multicentre, pragmatic randomised trial (with parallel preference groups). Setting 21 hospitals in the United Kingdom. Participants 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. Intervention The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. Main outcome measures The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. Main results Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. Conclusion At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. Trial registration ISRCTN15517081. PMID:19074946

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial.

PubMed

Grant, Adrian M; Wileman, Samantha M; Ramsay, Craig R; Mowat, N Ashley; Krukowski, Zygmunt H; Heading, Robert C; Thursz, Mark R; Campbell, Marion K

2008-12-15

To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). Multicentre, pragmatic randomised trial (with parallel preference groups). 21 hospitals in the United Kingdom. 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. ISRCTN15517081.

PC6 acupoint stimulation for the prevention of postcardiac surgery nausea and vomiting: a protocol for a two-group, parallel, superiority randomised clinical trial

PubMed Central

Cooke, Marie; Rickard, Claire; Rapchuk, Ivan; Shekar, Kiran; Marshall, Andrea P; Comans, Tracy; Doi, Suhail; McDonald, John; Spooner, Amy

2014-01-01

Introduction Postoperative nausea and vomiting (PONV) are frequent but unwanted complications for patients following anaesthesia and cardiac surgery, affecting at least a third of patients, despite pharmacological treatment. The primary aim of the proposed research is to test the efficacy of PC6 acupoint stimulation versus placebo for reducing PONV in cardiac surgery patients. In conjunction with this we aim to develop an understanding of intervention fidelity and factors that support, or impede, the use of PC6 acupoint stimulation, a knowledge translation approach. Methods and analysis 712 postcardiac surgery participants will be recruited to take part in a two-group, parallel, superiority, randomised controlled trial. Participants will be randomised to receive a wrist band on each wrist providing acupressure to PC six using acupoint stimulation or a placebo. Randomisation will be computer generated, use randomly varied block sizes, and be concealed prior to the enrolment of each patient. The wristbands will remain in place for 36 h. PONV will be evaluated by the assessment of both nausea and vomiting, use of rescue antiemetics, quality of recovery and cost. Patient satisfaction with PONV care will be measured and clinical staff interviewed about the clinical use, feasibility, acceptability and challenges of using acupressure wristbands for PONV. Ethics and dissemination Ethics approval will be sought from appropriate Human Research Ethics Committee/s before start of the study. A systematic review of the use of wrist acupressure for PC6 acupoint stimulation reported minor side effects only. Study progress will be reviewed by a Data Safety Monitoring Committee (DSMC) for nausea and vomiting outcomes at n=350. Dissemination of results will include conference presentations at national and international scientific meetings and publications in peer-reviewed journals. Study participants will receive a one-page lay-summary of results. Trial registration number Australian New Zealand Clinical Trials Registry—ACTRN12614000589684. PMID:25394818

Capillary array scanner for time-resolved detection and identification of fluorescently labelled DNA fragments.

PubMed

Neumann, M; Herten, D P; Dietrich, A; Wolfrum, J; Sauer, M

2000-02-25

The first capillary array scanner for time-resolved fluorescence detection in parallel capillary electrophoresis based on semiconductor technology is described. The system consists essentially of a confocal fluorescence microscope and a x,y-microscope scanning stage. Fluorescence of the labelled probe molecules was excited using a short-pulse diode laser emitting at 640 nm with a repetition rate of 50 MHz. Using a single filter system the fluorescence decays of different labels were detected by an avalanche photodiode in combination with a PC plug-in card for time-correlated single-photon counting (TCSPC). The time-resolved fluorescence signals were analyzed and identified by a maximum likelihood estimator (MLE). The x,y-microscope scanning stage allows for discontinuous, bidirectional scanning of up to 16 capillaries in an array, resulting in longer fluorescence collection times per capillary compared to scanners working in a continuous mode. Synchronization of the alignment and measurement process were developed to allow for data acquisition without overhead. Detection limits in the subzeptomol range for different dye molecules separated in parallel capillaries have been achieved. In addition, we report on parallel time-resolved detection and separation of more than 400 bases of single base extension DNA fragments in capillary array electrophoresis. Using only semiconductor technology the presented technique represents a low-cost alternative for high throughput DNA sequencing in parallel capillaries.

Vibrating vaginal balls to improve pelvic floor muscle performance in women after childbirth: a protocol for a randomised controlled feasibility trial.

PubMed

Oblasser, Claudia; McCourt, Christine; Hanzal, Engelbert; Christie, Janice

2016-04-01

This paper presents a feasibility trial protocol the purpose of which is to prepare for a future randomised controlled trial to determine the effectiveness of vibrating vaginal pelvic floor training balls for postpartum pelvic floor muscle rehabilitation. Vibrating vaginal pelvic floor training balls are available in Austria to enhance women's pelvic floor muscles and thus prevent or treat urinary incontinence and other pelvic floor problems following childbirth. Nonetheless, there is currently little empirical knowledge to substantiate their use or assess their relative effectiveness in comparison to current standard care, which involves pelvic floor muscle exercises. Single blind, randomised controlled feasibility trial with two parallel groups. It is planned to recruit 56 postpartum women in Vienna, who will be randomised into one of two intervention groups to use either vibrating vaginal balls or a comparator pelvic floor muscle exercises for 12 weeks. As this is a feasibility study, study design features (recruitment, selection, randomisation, intervention concordance, data collection methods and tools) will be assessed and participants' views and experiences will be surveyed. Tested outcome measures, collected before and after the intervention, will be pelvic floor muscle performance as reported by participants and measured by perineometry. Descriptive and inferential statistics and content analysis will serve the preparation of the future trial. The results of this feasibility trial will inform the design and conduct of a full randomised controlled trial and provide insight into the experiences of women regarding the interventions and study participation. © 2015 John Wiley & Sons Ltd.

A Randomised, Controlled Comparison of Low-Dose Polyethylene Glycol 3350 plus Electrolytes with Ispaghula Husk in the Treatment of Adults with Chronic Functional Constipation.

PubMed

Wang, Hui-Ji; Liang, Xiao-Mei; Yu, Zhong-Lin; Zhou, Li-Ya; Lin, San-Ren; Geraint, Mike

2004-01-01

To compare the efficacy and safety of polyethylene glycol (PEG) 3350 plus electrolytes (PEG+E; Movicol((R))) with that of ispaghula husk (psyllium; Konsyl((R))) in the treatment of constipation. Male or female adults with chronic functional constipation. This was a randomised, controlled, open-label, parallel-group trial. Study treatment was either PEG+E 13.8g/sachet dissolved in water twice daily or ispaghula husk 3.5g/sachet dissolved in water twice daily for a period of 2 weeks. Assessments were at baseline and after 1 and 2 weeks' therapy and by patient daily diary card. The primary outcome measures were weekly defaecation rate, stool consistency according to the Bristol Stool Form scale, time to first defaecation, and overall efficacy, which combined defaecation rate, stool consistency and difficulty on defaecation. Adverse effects were recorded and laboratory assessments were performed before and at the end of the treatment period. Sixty-three patients were randomised to each treatment group. Treatment was highly effective in 50/63 patients in the PEG+E group compared with 26/63 in the ispaghula husk group, and the overall efficacy rates were 92% and 73%, respectively (p = 0.005). PEG+E increased the mean weekly defaecation rate from 1.18 (SD 0.77) at baseline to 7.95 (SD 3.49) after 1 week and 8.48 (SD 3.55) after 2 weeks. In the ispaghula husk group the mean weekly defaecation rate increased from 1.33 (SD 0.68) at baseline to 5.33 (SD 2.81) after 1 week and to 5.71 (SD 2.49) after 2 weeks. The treatment differences for defaecation rates were all statistically significant (p < 0.001). Two weeks of treatment with PEG+E or ispaghula husk normalised stools in 55/63 (87.3%) and 42/63 (66.7%) of patients (p < 0.001). The incidence of adverse effects did not differ between groups and none were serious or required any treatment. Laboratory evaluations found no adverse effect from either treatment. The present study demonstrated that low-dose PEG 3350 plus electrolytes is more effective and more rapid in its onset of action than ispaghula husk, and is equally well tolerated.

Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study

PubMed Central

van de Hei, Susanne; McKinstry, Steven; Bardsley, George; Weatherall, Mark; Beasley, Richard; Fingleton, James

2018-01-01

Objective To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. Design Open label, randomised, controlled feasibility study. Setting Single-centre research institute in New Zealand recruiting participants from the community. Participants 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. Interventions Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). Primary and secondary outcome measures The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling ‘a lot better’ compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. Results In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (−6.4, 95% CI −9.4 to −3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. Conclusions This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. Trial registration number ACTRN12616000470493; Results. PMID:29593018

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

PubMed

Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

2016-05-01

Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

PubMed

Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

2009-05-16

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272). This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy. Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a prior history - an open-label randomised trial (the EPPI trial): study protocol.

PubMed

Groom, K M; McCowan, L M; Stone, P R; Chamley, L C; McLintock, C

2016-11-22

Preeclampsia and intrauterine fetal growth restriction (IUGR) are two of the most common causes of maternal and perinatal morbidity and mortality. Current methods of predicting those at most risk of these conditions remain relatively poor, and in clinical practice past obstetric history remains the most commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium have been demonstrated to have a modest effect on risk reduction. Several observational studies and randomised trials suggest that low molecular weight heparin (LMWH) therapy may confer some benefit. This is a multicentre open label randomised controlled trial to determine the effect of the LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in women at high risk due to their past obstetric history in addition to standard high risk care for all participants. A singleton pregnancy >6 +0 and <16 +0 weeks gestation with most recent prior pregnancy with duration >12 weeks having; (1) preeclampsia delivered <36 +0 weeks, (2) Small for gestational age (SGA) infant <10 th customised birthweight centile delivered <36 +0 weeks or, (3) SGA infant ≤3 rd customised birthweight centile delivered at any gestation. Randomisation is stratified for maternal thrombophilia status and women are randomly assigned to 'standard high risk care' or 'standard high risk care' plus enoxaparin 40 mg from recruitment until 36 +0 weeks or delivery, whichever occurs sooner. Standard high risk care includes the use of aspirin 100 mg daily and calcium 1000-1500 mg daily (unless only had previous SGA with no preeclampsia). The primary outcome is preeclampsia and/or SGA <5 th customised birthweight centile. Analysis will be by intention to treat. The EPPI trial has more focussed and clinically relevant inclusion criteria than other randomised trials with a more restricted composite primary outcome. The inclusion of standard use of aspirin (and calcium) for all participants will help to ensure that any differences observed in outcome are likely to be related to enoxaparin use. These data will make a significant contribution to future meta-analyses and systematic reviews on the use of LMWH for the prevention of placental mediated conditions. ACTRN12609000699268 Australian New Zealand Clinical Trials Registry. Date registered 13/Aug/2009 (prospective registration).

Immediate interruption of sedation compared with usual sedation care in critically ill postoperative patients (SOS-Ventilation): a randomised, parallel-group clinical trial.

PubMed

Chanques, Gerald; Conseil, Matthieu; Roger, Claire; Constantin, Jean-Michel; Prades, Albert; Carr, Julie; Muller, Laurent; Jung, Boris; Belafia, Fouad; Cissé, Moussa; Delay, Jean-Marc; de Jong, Audrey; Lefrant, Jean-Yves; Futier, Emmanuel; Mercier, Grégoire; Molinari, Nicolas; Jaber, Samir

2017-10-01

Avoidance of excessive sedation and subsequent prolonged mechanical ventilation in intensive care units (ICUs) is recommended, but no data are available for critically ill postoperative patients. We hypothesised that in such patients stopping sedation immediately after admission to the ICU could reduce unnecessary sedation and improve patient outcomes. We did a randomised, parallel-group, clinical trial at three ICUs in France. Stratified randomisation with minimisation (1:1 via a restricted web platform) was used to assign eligible patients (aged ≥18 years, admitted to an ICU after abdominal surgery, and expected to require at least 12 h of mechanical ventilation because of a critical illness defined by a Sequential Organ Failure Assessment score >1 for any organ, but without severe acute respiratory distress syndrome or brain injury) to usual sedation care provided according to recommended practices (control group) or to immediate interruption of sedation (intervention group). The primary outcome was the time to successful extubation (defined as the time from randomisation to the time of extubation [or tracheotomy mask] for at least 48 h). All patients who underwent randomisation (except for those who were excluded after randomisation) were included in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT01486121. Between Dec 2, 2011, and Feb 27, 2014, 137 patients were randomly assigned to the control (n=68) or intervention groups (n=69). In the intention-to-treat analysis, time to successful extubation was significantly lower in the intervention group than in the control group (median 8 h [IQR 4-36] vs 50 h [29-93], group difference -33·6 h [95% CI -44·9 to -22·4]; p<0·0001). The adjusted hazard ratio was 5·2 (95% CI 3·1-8·8, p<0·0001). Immediate interruption of sedation in critically ill postoperative patients with organ dysfunction who were admitted to the ICU after abdominal surgery improved outcomes compared with usual sedation care. These findings support interruption of sedation in these patients following transfer from the operating room. Délégation à la Recherche Clinique et à l'Innovation du Groupement de Coopération Sanitaire de la Mission d'Enseignement, de Recherche, de Référence et d'Innovation (DRCI-GCS-MERRI) de Montpellier-Nîmes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beyond the treatment effect: Evaluating the effects of patient preferences in randomised trials.

PubMed

Walter, S D; Turner, R; Macaskill, P; McCaffery, K J; Irwig, L

2017-02-01

The treatments under comparison in a randomised trial should ideally have equal value and acceptability - a position of equipoise - to study participants. However, it is unlikely that true equipoise exists in practice, because at least some participants may have preferences for one treatment or the other, for a variety of reasons. These preferences may be related to study outcomes, and hence affect the estimation of the treatment effect. Furthermore, the effects of preferences can sometimes be substantial, and may even be larger than the direct effect of treatment. Preference effects are of interest in their own right, but they cannot be assessed in the standard parallel group design for a randomised trial. In this paper, we describe a model to represent the impact of preferences on trial outcomes, in addition to the usual treatment effect. In particular, we describe how outcomes might differ between participants who would choose one treatment or the other, if they were free to do so. Additionally, we investigate the difference in outcomes depending on whether or not a participant receives his or her preferred treatment, which we characterise through a so-called preference effect. We then discuss several study designs that have been proposed to measure and exploit data on preferences, and which constitute alternatives to the conventional parallel group design. Based on the model framework, we determine which of the various preference effects can or cannot be estimated with each design. We also illustrate these ideas with some examples of preference designs from the literature.

A review of evidence of health benefit from artificial neural networks in medical intervention.

PubMed

Lisboa, P J G

2002-01-01

The purpose of this review is to assess the evidence of healthcare benefits involving the application of artificial neural networks to the clinical functions of diagnosis, prognosis and survival analysis, in the medical domains of oncology, critical care and cardiovascular medicine. The primary source of publications is PUBMED listings under Randomised Controlled Trials and Clinical Trials. The rĵle of neural networks is introduced within the context of advances in medical decision support arising from parallel developments in statistics and artificial intelligence. This is followed by a survey of published Randomised Controlled Trials and Clinical Trials, leading to recommendations for good practice in the design and evaluation of neural networks for use in medical intervention.

Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy.

PubMed

Ziada, Dina H; Soliman, Hanan H; El Yamany, Saher A; Hamisa, Manal F; Hasan, Azza M

2013-09-01

Minimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE. This is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine+glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4weeks. The probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho+mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group. Both probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3.

PubMed

Yale, Jean-François; Pettus, Jeremy Hodson; Brito-Sanfiel, Miguel; Lavalle-Gonzalez, Fernando; Merino-Trigo, Ana; Stella, Peter; Chevalier, Soazig; Buzzetti, Raffaella

2018-01-01

To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs. A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, open-label, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use. Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups. Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use. ClinicalTrials.gov NCT01499095; NCT01676220.

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol

PubMed Central

Figueras, Francesc; Gratacos, Eduard; Rial, Marta; Gull, Ilan; Krofta, Ladislav; Lubusky, Marek; Rogelio, Cruz-Martinez; Mónica, Cruz-Lemini; Miguel, Martinez-Rodriguez; Socias, Pamela; Aleuanlli, Cristina; Cordero, Mauro C Parra

2017-01-01

Introduction Fetal growth restriction (FGR) affects 5%–10% of all pregnancies, contributing to 30%–50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. Methods and analysis The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19+0–22+6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36+0–37+6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36+0–37+6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. Ethics and dissemination The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number NCT02907242; pre-results. PMID:28619771

Energy and traffic light labelling have no impact on parent and child fast food selection.

PubMed

Dodds, Pennie; Wolfenden, Luke; Chapman, Kathy; Wellard, Lyndal; Hughes, Clare; Wiggers, John

2013-10-25

Labelling of food from fast food restaurants at point-of-purchase has been suggested as one strategy to reduce population energy consumption and contribute to reductions in obesity prevalence. The aim of this study was to examine the effects of energy and single traffic light labelling systems on the energy content of child and adult intended food purchases. The study employed a randomised controlled trial design. English speaking parents of children aged between three and 12 years were recruited from an existing research cohort. Participants were mailed one of three hypothetical fast food menus. Menus differed in their labelling technique- either energy labels, single traffic light labels, or a no-label control. Participants then completed a telephone survey which assessed intended food purchases for both adult and child. The primary trial outcome was total energy of intended food purchase. A total of 329 participants completed the follow-up telephone interview. Eighty-two percent of the energy labelling group and 96% of the single traffic light labelling group reported noticing labelling information on their menu. There were no significant differences in total energy of intended purchases of parents, or intended purchases made by parents for children, between the menu labelling groups, or between menu labelling groups by socio-demographic subgroups. This study provided no evidence to suggest that energy labelling or single traffic light labelling alone were effective in reducing the energy of fast food items selected from hypothetical fast food menus for purchase. Additional complementary public health initiatives promoting the consumption of healthier foods identified by labelling, and which target other key drivers of menu item selection in this setting may be required. Copyright © 2013. Published by Elsevier Ltd.

The impact of nutritional labels and socioeconomic status on energy intake. An experimental field study.

PubMed

Crockett, Rachel A; Jebb, Susan A; Hankins, Matthew; Marteau, Theresa M

2014-10-01

There is some evidence for paradoxical effects of nutritional labelling on energy intake particularly amongst restrained eaters and those with a higher body mass index (BMI) resulting in greater consumption of energy from foods with a positive health message (e.g. "low-fat") compared with the same foods, unlabelled. This study aimed to investigate, in a UK general population sample, the likelihood of paradoxical effects of nutritional labelling on energy intake. Participants (n = 287) attended a London cinema and were offered a large tub of salted or toffee popcorn. Participants were randomised to receive their selected flavour with one of three labels: a green low-fat label, a red high-fat label or no label. Participants watched two film clips while completing measures of demographic characteristics, emotional state and taste of the popcorn. Following the experiment, popcorn consumption was measured. There were no main effects of nutritional labelling on consumption. Contrary to predictions neither BMI nor weight concern moderated the effect of label on consumption. There was a three-way interaction between low-fat label, weight concern and socioeconomic status (SES) such that weight-concerned participants of higher SES who saw a low-fat label consumed more than weight unconcerned participants of similar SES (t = -2.7, P = .04). By contrast, weight-concerned participants of lower SES seeing either type of label, consumed less than those seeing no label (t = -2.04, P = .04). Nutritional labelling may have different effects in different socioeconomic groups. Further studies are required to understand fully the possible contribution of food labelling to health inequalities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial.

PubMed

Reni, Michele; Cereda, Stefano; Milella, Michele; Novarino, Anna; Passardi, Alessandro; Mambrini, Andrea; Di Lucca, Giuseppe; Aprile, Giuseppe; Belli, Carmen; Danova, Marco; Bergamo, Francesca; Franceschi, Enrico; Fugazza, Clara; Ceraulo, Domenica; Villa, Eugenio

2013-11-01

New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status >50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α .10; β .10, the target accrual was 26 patients per arm. 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P<0.01); 2 y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population. Copyright © 2013 Elsevier Ltd. All rights reserved.

5-a-day fruit and vegetable food product labels: reduced fruit and vegetable consumption following an exaggerated compared to a modest label.

PubMed

Appleton, K M; Pidgeon, H J

2018-05-15

Food product labels based on the WHO 5-a-day fruit and vegetable (FV) message are becoming increasingly common, but these labels may impact negatively on complementary or subsequent FV consumption. This study aimed to investigate the impact of a '3 of your 5-a-day' versus a '1 of your 5-a-day' smoothie product label on subsequent FV consumption. Using an acute experimental design, 194 participants (90 males, 104 females) were randomised to consume a smoothie labelled as either '3 of your 5-a-day' (N = 97) or '1 of your 5-a-day' (N = 97) in full, following a usual breakfast. Subsequent FV consumption was measured for the rest of the day using 24-h recall. Usual FV consumption was also assessed via 24-h recall for the day before the study. Regression analyses revealed a significantly lower subsequent FV consumption following smoothies displaying the '3 of your 5-a-day' label compared to the '1 of your 5-a-day' label (Beta = - 0.15, p = 0.04). Secondary analyses revealed these effects to be driven mainly by changes to consumption in usual high FV consumers, in females and in vegetable as opposed to fruit consumption. These findings demonstrate a role for label information in food intake, and the potential negative impacts of an exaggerated food product label on healthy food consumption and healthy dietary profiles.

Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial.

PubMed

Rodger, Marc A; Hague, William M; Kingdom, John; Kahn, Susan R; Karovitch, Alan; Sermer, Mathew; Clement, Anne Marie; Coat, Suzette; Chan, Wee Shian; Said, Joanne; Rey, Evelyne; Robinson, Sue; Khurana, Rshmi; Demers, Christine; Kovacs, Michael J; Solymoss, Susan; Hinshaw, Kim; Dwyer, James; Smith, Graeme; McDonald, Sarah; Newstead-Angel, Jill; McLeod, Anne; Khandelwal, Meena; Silver, Robert M; Le Gal, Gregoire; Greer, Ian A; Keely, Erin; Rosene-Montella, Karen; Walker, Mark; Wells, Philip S

2014-11-08

Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4-24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8-26·3%]; risk difference -1·8% [95% CI -10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI -6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3-18·4; p=0·01). Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, and Pharmacia and UpJohn. Copyright © 2014 Elsevier Ltd. All rights reserved.

Labeled trees and the efficient computation of derivations

NASA Technical Reports Server (NTRS)

Grossman, Robert; Larson, Richard G.

1989-01-01

The effective parallel symbolic computation of operators under composition is discussed. Examples include differential operators under composition and vector fields under the Lie bracket. Data structures consisting of formal linear combinations of rooted labeled trees are discussed. A multiplication on rooted labeled trees is defined, thereby making the set of these data structures into an associative algebra. An algebra homomorphism is defined from the original algebra of operators into this algebra of trees. An algebra homomorphism from the algebra of trees into the algebra of differential operators is then described. The cancellation which occurs when noncommuting operators are expressed in terms of commuting ones occurs naturally when the operators are represented using this data structure. This leads to an algorithm which, for operators which are derivations, speeds up the computation exponentially in the degree of the operator. It is shown that the algebra of trees leads naturally to a parallel version of the algorithm.

Regular treatment with formoterol versus regular treatment with salmeterol for chronic asthma: serious adverse events

PubMed Central

Cates, Christopher J; Lasserson, Toby J

2014-01-01

Background An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in previous Cochrane reviews. Objectives We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol. Search methods We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked manufacturers’ websites of clinical trial registers for unpublished trial data and also checked Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was January 2012. Selection criteria We included controlled, parallel-design clinical trials on patients of any age and with any severity of asthma if they randomised patients to treatment with regular formoterol versus regular salmeterol (without randomised inhaled corticosteroids), and were of at least 12 weeks’ duration. Data collection and analysis Two authors independently selected trials for inclusion in the review and extracted outcome data. We sought unpublished data on mortality and serious adverse events from the sponsors and authors. Main results The review included four studies (involving 1116 adults and 156 children). All studies were open label and recruited patients who were already taking inhaled corticosteroids for their asthma, and all studies contributed data on serious adverse events. All studies compared formoterol 12 μg versus salmeterol 50 μg twice daily. The adult studies were all comparing Foradil Aerolizer with Serevent Diskus, and the children’s study compared Oxis Turbohaler to Serevent Accuhaler. There was only one death in an adult (which was unrelated to asthma) and none in children, and there were no significant differences in non-fatal serious adverse events comparing formoterol to salmeterol in adults (Peto odds ratio (OR) 0.77; 95% confidence interval (CI) 0.46 to 1.28), or children (Peto OR 0.95; 95% CI 0.06 to 15.33). Over a six-month period, in studies involving adults that contributed to this analysis, the percentages with serious adverse events were 5.1% for formoterol and 6.4% for salmeterol; and over a three-month period the percentages of children with serious adverse events were 1.3% for formoterol and 1.3% for salmeterol. Authors’ conclusions We identified four studies comparing regular formoterol to regular salmeterol (without randomised inhaled corticosteroids, but all participants were on regular background inhaled corticosteroids). The events were infrequent and consequently too few patients have been studied to allow any firm conclusions to be drawn about the relative safety of formoterol and salmeterol. Asthma-related serious adverse events were rare and there were no reported asthma-related deaths. PMID:22419326

Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk.

PubMed

Müller-Wieland, Dirk; Leiter, Lawrence A; Cariou, Bertrand; Letierce, Alexia; Colhoun, Helen M; Del Prato, Stefano; Henry, Robert R; Tinahones, Francisco J; Aurand, Lisa; Maroni, Jaman; Ray, Kausik K; Bujas-Bobanovic, Maja

2017-05-25

Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator. DM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ≥100 mg/dl [≥2.59 mmol/l], and triglycerides ≥150 and <500 mg/dl [≥1.70 and <5.65 mmol/l]) with documented atherosclerotic cardiovascular disease or ≥1 additional cardiovascular risk factor. Participants were randomised (2:1) to alirocumab 75 mg every 2 weeks (Q2W) or lipid-lowering usual care on top of maximally tolerated statin (or no statin if intolerant). If randomised to usual care, investigators were able to add their pre-specified choice of one of the following to the patient's current statin regimen: ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid, in accordance with local standard-of-care. Alirocumab-treated individuals with non-HDL-C ≥100 mg/dl at week 8 will undergo a blinded dose increase to 150 mg Q2W at week 12. The primary efficacy endpoint is non-HDL-C change from baseline to week 24 with alirocumab versus usual care; other lipid levels (including LDL-C), glycaemia-related measures, safety and tolerability will also be assessed. Alirocumab will be compared to fenofibrate in a secondary analysis. Recruitment completed with 413 individuals randomised in 14 countries worldwide. Results of this trial are expected in the second quarter of 2017. ODYSSEY DM-DYSLIPIDEMIA will provide information on the efficacy and safety of alirocumab versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk using non-HDL-C as the primary efficacy endpoint. Trial registration NCT02642159 (registered December 24, 2015).

Neuromuscular Adaptations to Eccentric Strength Training in Children and Adolescents with Cerebral Palsy

ERIC Educational Resources Information Center

Reid, Siobhan; Hamer, Peter; Alderson, Jacqueline; Lloyd, David

2010-01-01

Aim: To determine the neuromuscular outcomes of an eccentric strength-training programme for children and adolescents with cerebral palsy (CP). Method: In this randomised, parallel-group trial with waiting control, 14 participants with CP (six males, eight females; mean age 11y, SD 2y range 9-15y), diagnosed with upper-limb spasticity were…

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX).

PubMed

Grant, A M; Cotton, S C; Boachie, C; Ramsay, C R; Krukowski, Z H; Heading, R C; Campbell, M K

2013-04-18

To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). Initial recruitment in 21 UK hospitals. Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations-most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. Current Controlled Trials ISRCTN15517081.

Topical Coconut Oil in Very Preterm Infants: An Open-Label Randomised Controlled Trial.

PubMed

Strunk, Tobias; Pupala, Sameer; Hibbert, Julie; Doherty, Dorota; Patole, Sanjay

2018-01-01

The immature fragile skin of preterm infants represents an inadequate protective barrier. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. Our aim was to evaluate feasibility, safety, and the effects of topical coconut oil on skin condition in very preterm infants. An open-label randomised controlled trial in preterm infants <30 weeks' gestation was conducted. Enrolled infants were randomised to receive either routine care or topical coconut oil (5 mL/kg) twice daily for 21 days, starting within 24 h of birth. The neonatal skin condition was the primary outcome, and was assessed using the Neonatal Skin Condition Score (NSCS) on days 1, 7, 14, and 21. The number of coconut oil applications was recorded to assess clinical feasibility and all enrolled infants were monitored for adverse effects of topical coconut application, such as skin irritation. A total of 72 infants born <30 weeks' gestation were enrolled (36 infants per arm), with comparable demographic characteristics. Topical application of coconut oil was feasible and without adverse effects. The NSCS was maintained in the coconut oil group throughout the intervention period, but deteriorated from a median (IQR) of 3 (3-4) on day 1 to 4 (4-4) on day 21 in the control group (p = 0.01). There were no differences in common neonatal outcomes, including sepsis, necrotising enterocolitis, retinopathy of prematurity, chronic lung disease, and mortality. Topical coconut oil maintained a better skin condition in very preterm infants without adverse effects. This simple, safe, and affordable intervention warrants further investigation. © 2017 S. Karger AG, Basel.

Do nutrition labels influence healthier food choices? Analysis of label viewing behaviour and subsequent food purchases in a labelling intervention trial.

PubMed

Ni Mhurchu, Cliona; Eyles, Helen; Jiang, Yannan; Blakely, Tony

2018-02-01

There are few objective data on how nutrition labels are used in real-world shopping situations, or how they affect dietary choices and patterns. The Starlight study was a four-week randomised, controlled trial of the effects of three different types of nutrition labels on consumer food purchases: Traffic Light Labels, Health Star Rating labels, or Nutrition Information Panels (control). Smartphone technology allowed participants to scan barcodes of packaged foods and receive randomly allocated labels on their phone screen, and to record their food purchases. The study app therefore provided objectively recorded data on label viewing behaviour and food purchases over a four-week period. A post-hoc analysis of trial data was undertaken to assess frequency of label use, label use by food group, and association between label use and the healthiness of packaged food products purchased. Over the four-week intervention, study participants (n = 1255) viewed nutrition labels for and/or purchased 66,915 barcoded packaged products. Labels were viewed for 23% of all purchased products, with decreasing frequency over time. Shoppers were most likely to view labels for convenience foods, cereals, snack foods, bread and bakery products, and oils. They were least likely to view labels for sugar and honey products, eggs, fish, fruit and vegetables, and meat. Products for which participants viewed the label and subsequently purchased the product during the same shopping episode were significantly healthier than products where labels were viewed but the product was not subsequently purchased: mean difference in nutrient profile score -0.90 (95% CI -1.54 to -0.26). In a secondary analysis of a nutrition labelling intervention trial, there was a significant association between label use and the healthiness of products purchased. Nutrition label use may therefore lead to healthier food purchases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial

PubMed Central

2013-01-01

Background Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials. Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. Design BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3. Discussion The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755). PMID:23835026

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

A multi-centre, parallel group superiority trial of silk therapeutic clothing compared to standard care for the management of eczema in children (CLOTHES Trial): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor F; Haines, Rachel H; Cowdell, Fiona; Sach, Tracey H; Dean, Taraneh; Pollock, Ian; Burrows, Nigel P; Buckley, Hannah; Batchelor, Jonathan; Williams, Hywel C; Lawton, Sandra; Brown, Sara J; Bradshaw, Lucy E; Ahmed, Amina; Montgomery, Alan A; Mitchell, Eleanor J; Thomas, Kim S

2015-09-02

Eczema is a chronic, itchy skin condition that can have a large impact on the quality of life of patients and their families. People with eczema are often keen to try out non-pharmacological therapies like silk therapeutic garments that could reduce itching or the damage caused by scratching. However, the effectiveness and cost-effectiveness of these garments in the management of eczema has yet to be proven. The CLOTHES Trial will test the hypothesis that 'silk therapeutic garments plus standard eczema care' is superior to 'standard care alone' for children with moderate to severe eczema. Parallel group, observer-blind, pragmatic, multi-centre randomised controlled trial of 6 months' duration. Three hundred children aged 1 to 15 years with moderate to severe eczema will be randomised (1:1) to receive silk therapeutic garments plus standard eczema care, or standard eczema care alone. Primary outcome is eczema severity, as assessed by trained and blinded investigators at 2, 4 and 6 months (using the Eczema Area and Severity Index (EASI)). Secondary outcomes include: patient-reported eczema symptoms (collected weekly for 6 months to capture long-term control); global assessment of severity; quality of life of the child, family and main carer; use of standard eczema treatments (emollients, corticosteroids applied topically, calcineurin inhibitors applied topically and wet wraps); frequency of infections; and cost-effectiveness. The acceptability and durability of the clothing will also be assessed, as will adherence to wearing the garments. A nested qualitative study will assess the views of a subset of children wearing the garments and their parents, and those of healthcare providers and commissioners. Randomisation uses a computer-generated sequence of permuted blocks of randomly varying size, stratified by recruiting hospital and child's age (< 2 years; 2 to 5 years; > 5 years), and concealed using a secure web-based system. The sequence of treatment allocations will remain concealed until randomisation and data collection are complete. Recruitment is taking place from November 2013 to May 2015, and the trial will be completed in 2016. Full details of results will be published in the National Institute for Health Research Journal series. Current Controlled Trials ISRCTN77261365 (registered 11 November 2013).

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

PubMed

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis). Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. Trial registration Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14. PMID:22540770

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

PubMed

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-08-02

To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Double blind randomised placebo controlled parallel group study. Hospital in Hampshire. 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Enzyme potentiated desensitisation showed no treatment effect in this study.

Impact of non-uniform correlation structure on sample size and power in multiple-period cluster randomised trials.

PubMed

Kasza, J; Hemming, K; Hooper, R; Matthews, Jns; Forbes, A B

2017-01-01

Stepped wedge and cluster randomised crossover trials are examples of cluster randomised designs conducted over multiple time periods that are being used with increasing frequency in health research. Recent systematic reviews of both of these designs indicate that the within-cluster correlation is typically taken account of in the analysis of data using a random intercept mixed model, implying a constant correlation between any two individuals in the same cluster no matter how far apart in time they are measured: within-period and between-period intra-cluster correlations are assumed to be identical. Recently proposed extensions allow the within- and between-period intra-cluster correlations to differ, although these methods require that all between-period intra-cluster correlations are identical, which may not be appropriate in all situations. Motivated by a proposed intensive care cluster randomised trial, we propose an alternative correlation structure for repeated cross-sectional multiple-period cluster randomised trials in which the between-period intra-cluster correlation is allowed to decay depending on the distance between measurements. We present results for the variance of treatment effect estimators for varying amounts of decay, investigating the consequences of the variation in decay on sample size planning for stepped wedge, cluster crossover and multiple-period parallel-arm cluster randomised trials. We also investigate the impact of assuming constant between-period intra-cluster correlations instead of decaying between-period intra-cluster correlations. Our results indicate that in certain design configurations, including the one corresponding to the proposed trial, a correlation decay can have an important impact on variances of treatment effect estimators, and hence on sample size and power. An R Shiny app allows readers to interactively explore the impact of correlation decay.

The effect of sugar-sweetened beverage front-of-pack labels on drink selection, health knowledge and awareness: An online randomised controlled trial.

PubMed

Billich, Natassja; Blake, Miranda R; Backholer, Kathryn; Cobcroft, Megan; Li, Vincy; Peeters, Anna

2018-06-04

Sugar-sweetened beverages (SSBs) provide little nutritional value and are associated with an increased risk of diet-related diseases. Despite this, SSB consumption is high globally. One emerging strategy aimed at reducing SSB consumption involves the use of front-of-pack (FOP) labels that clearly identify the risks associated with SSB consumption. The aim of this research study was to determine whether FOP labels with a graphic warning, text warning, sugar information (with the number of teaspoons of added sugar) or Health Star Rating (HSR) reduces intended choice of a SSB in an online choice experiment with young Australian adults. 994 participants were recruited and completed the online choice experiment. Compared to the control group who were not exposed to a label, the graphic warning, text warning, sugar information and HSR labels all significantly reduced selection of a SSB in the choice scenario. The magnitude of effect was greatest for the graphic warning label (OR 0.22 95% CI 0.14-0.35). Compared to the control group, only the HSR label significantly increased selections of the high HSR drinks (OR 2.18 95% CI 1.20-3.97). FOP labels, particularly those with graphic warnings, have the potential to reduce intended SSB purchases. Labels that also identify healthier alternatives may influence consumers to substitute SSBs with healthier drinks. Copyright © 2018. Published by Elsevier Ltd.

COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome.

PubMed

Roquilly, Antoine; Lasocki, Sigismond; Moyer, Jean Denis; Huet, Olivier; Perrigault, Pierre François; Dahyot-Fizelier, Claire; Seguin, Philippe; Sharshar, Tarek; Geeraerts, Thomas; Remerand, Francis; Feuillet, Fanny; Asehnoune, Karim

2017-09-24

Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI. The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR. The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery. Trial registration number is NCT03143751. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial.

PubMed

Camenzind, Edoardo; Wijns, William; Mauri, Laura; Kurowski, Volkhard; Parikh, Keyur; Gao, Runlin; Bode, Christoph; Greenwood, John P; Boersma, Eric; Vranckx, Pascal; McFadden, Eugene; Serruys, Patrick W; O'Neil, William W; Jorissen, Brenda; Van Leeuwen, Frank; Steg, Ph Gabriel

2012-10-20

We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Medtronic, Inc. Copyright © 2012 Elsevier Ltd. All rights reserved.

Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

PubMed

Corbacioglu, Selim; Cesaro, Simone; Faraci, Maura; Valteau-Couanet, Dominique; Gruhn, Bernd; Rovelli, Attilio; Boelens, Jaap J; Hewitt, Annette; Schrum, Johanna; Schulz, Ansgar S; Müller, Ingo; Stein, Jerry; Wynn, Robert; Greil, Johann; Sykora, Karl-Walter; Matthes-Martin, Susanne; Führer, Monika; O'Meara, Anne; Toporski, Jacek; Sedlacek, Petr; Schlegel, Paul G; Ehlert, Karoline; Fasth, Anders; Winiarski, Jacek; Arvidson, Johan; Mauz-Körholz, Christine; Ozsahin, Hulya; Schrauder, Andre; Bader, Peter; Massaro, Joseph; D'Agostino, Ralph; Hoyle, Margaret; Iacobelli, Massimo; Debatin, Klaus-Michael; Peters, Christina; Dini, Giorgio

2012-04-07

Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Gentium SpA, European Group for Blood and Marrow Transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study.

PubMed

Rorie, David A; Rogers, Amy; Mackenzie, Isla S; Ford, Ian; Webb, David J; Willams, Bryan; Brown, Morris; Poulter, Neil; Findlay, Evelyn; Saywood, Wendy; MacDonald, Thomas M

2016-02-09

Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10,269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. TIME has ethical approval in the UK, and results will be published in a peer-reviewed journal. UKCRN17071; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PAin SoluTions In the Emergency Setting (PASTIES); a protocol for two open-label randomised trials of patient-controlled analgesia (PCA) versus routine care in the emergency department

PubMed Central

Smith, Jason E; Rockett, Mark; Squire, Rosalyn; Hayward, Christopher J; Creanor, Siobhan; Ewings, Paul; Barton, Andy; Pritchard, Colin; Benger, Jonathan Richard

2013-01-01

Introduction Pain is the commonest reason that patients present to an emergency department (ED), but it is often not treated effectively. Patient controlled analgesia (PCA) is used in other hospital settings but there is little evidence to support its use in emergency patients. We describe two randomised trials aiming to compare PCA to nurse titrated analgesia (routine care) in adult patients who present to the ED requiring intravenous opioid analgesia for the treatment of moderate to severe pain and are subsequently admitted to hospital. Methods and analysis Two prospective multi-centre open-label randomised trials of PCA versus routine care in emergency department patients who require intravenous opioid analgesia followed by admission to hospital; one trial involving patients with traumatic musculoskeletal injuries and the second involving patients with non-traumatic abdominal pain. In each trial, 200 participants will be randomised to receive either routine care or PCA, and followed for the first 12 h of their hospital stay. The primary outcome measure is hourly pain score recorded by the participant using a visual analogue scale (VAS) over the 12 h study period, with the primary statistical analyses based on the area under the curve of these pain scores. Secondary outcomes include total opioid use, side effects, time spent asleep, patient satisfaction, length of hospital stay and incremental cost effectiveness ratio. Ethics and dissemination The study is approved by the South Central—Southampton A Research Ethics Committee (REC reference 11/SC/0151). Data collection will be completed by August 2013, with statistical analyses starting after all final data queries are resolved. Dissemination plans include presentations at local, national and international scientific meetings held by relevant Colleges and societies. Publications should be ready for submission during 2014. A lay summary of the results will be available to study participants on request, and disseminated via a publically accessible website. Registration details The study is registered with the European Clinical Trials Database (EudraCT Number: 2011-000194-31) and is on the ISCRTN register (ISRCTN25343280). PMID:23418302

Burst-mode optical label processor with ultralow power consumption.

PubMed

Ibrahim, Salah; Nakahara, Tatsushi; Ishikawa, Hiroshi; Takahashi, Ryo

2016-04-04

A novel label processor subsystem for 100-Gbps (25-Gbps × 4λs) burst-mode optical packets is developed, in which a highly energy-efficient method is pursued for extracting and interfacing the ultrafast packet-label to a CMOS-based processor where label recognition takes place. The method involves performing serial-to-parallel conversion for the label bits on a bit-by-bit basis by using an optoelectronic converter that is operated with a set of optical triggers generated in a burst-mode manner upon packet arrival. Here we present three key achievements that enabled a significant reduction in the total power consumption and latency of the whole subsystem; 1) based on a novel operation mechanism for providing amplification with bit-level selectivity, an optical trigger pulse generator, that consumes power for a very short duration upon packet arrival, is proposed and experimentally demonstrated, 2) the energy of optical triggers needed by the optoelectronic serial-to-parallel converter is reduced by utilizing a negative-polarity signal while employing an enhanced conversion scheme entitled the discharge-or-hold scheme, 3) the necessary optical trigger energy is further cut down by half by coupling the triggers through the chip's backside, whereas a novel lens-free packaging method is developed to enable a low-cost alignment process that works with simple visual observation.

Boltzmann Transport Code Update: Parallelization and Integrated Design Updates

NASA Technical Reports Server (NTRS)

Heinbockel, J. H.; Nealy, J. E.; DeAngelis, G.; Feldman, G. A.; Chokshi, S.

2003-01-01

The on going efforts at developing a web site for radiation analysis is expected to result in an increased usage of the High Charge and Energy Transport Code HZETRN. It would be nice to be able to do the requested calculations quickly and efficiently. Therefore the question arose, "Could the implementation of parallel processing speed up the calculations required?" To answer this question two modifications of the HZETRN computer code were created. The first modification selected the shield material of Al(2219) , then polyethylene and then Al(2219). The modified Fortran code was labeled 1SSTRN.F. The second modification considered the shield material of CO2 and Martian regolith. This modified Fortran code was labeled MARSTRN.F.

Evidence That Counts: 12 Teacher-Led Randomised Controlled Trials and Other Styles of Experimental Research

ERIC Educational Resources Information Center

Churches, Richard; McAleavy, Tony

2016-01-01

This publication contains 12 (A3 open-out) poster-style reports of teacher experimental research. The style of presentation parallels the type of preliminary reporting common at academic conferences and postgraduate events. At the same time, it aims to act as a form of short primer to introduce teachers to the basic options that there are when…

Health trainer-led motivational intervention plus usual care for people under community supervision compared with usual care alone: a study protocol for a parallel-group pilot randomised controlled trial (STRENGTHEN).

PubMed

Thompson, Tom P; Callaghan, Lynne; Hazeldine, Emma; Quinn, Cath; Walker, Samantha; Byng, Richard; Wallace, Gary; Creanor, Siobhan; Green, Colin; Hawton, Annie; Annison, Jill; Sinclair, Julia; Senior, Jane; Taylor, Adrian H

2018-06-04

People with experience of the criminal justice system typically have worse physical and mental health, lower levels of mental well-being and have less healthy lifestyles than the general population. Health trainers have worked with offenders in the community to provide support for lifestyle change, enhance mental well-being and signpost to appropriate services. There has been no rigorous evaluation of the effectiveness and cost-effectiveness of providing such community support. This study aims to determine the feasibility and acceptability of conducting a randomised trial and delivering a health trainer intervention to people receiving community supervision in the UK. A multicentre, parallel, two-group randomised controlled trial recruiting 120 participants with 1:1 individual allocation to receive support from a health trainer and usual care or usual care alone, with mixed methods process evaluation. Participants receive community supervision from an offender manager in either a Community Rehabilitation Company or the National Probation Service. If they have served a custodial sentence, then they have to have been released for at least 2 months. The supervision period must have at least 7 months left at recruitment. Participants are interested in receiving support to change diet, physical activity, alcohol use and smoking and/or improve mental well-being. The primary outcome is mental well-being with secondary outcomes related to smoking, physical activity, alcohol consumption and diet. The primary outcome will inform sample size calculations for a definitive trial. The study has been approved by the Health and Care Research Wales Ethics Committee (REC reference 16/WA/0171). Dissemination will include publication of the intervention development process and findings for the stated outcomes, parallel process evaluation and economic evaluation in peer-reviewed journals. Results will also be disseminated to stakeholders and trial participants. ISRCTN80475744; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II).

PubMed

Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Emborg, Charlotte; Jepsen, Jens Richardt Mollegaard; Fagerlund, Birgitte; Gluud, Christian; Mors, Ole; Hjorthøj, Carsten; Nordentoft, Merete

2017-01-12

To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual. Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site. Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark. 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203). OPUS treatment consists of three core elements-modified assertive community treatment, family involvement, and social skill training-with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment. Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation. Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference -0.10 (95% confidence interval -0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group. This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment.Trial registration Clinicaltrial.gov NCT00914238. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy

PubMed Central

Lähteenmäki, Pekka; Haukkamaa, Maija; Puolakka, Jukka; Riikonen, Ulla; Sainio, Susanna; Suvisaari, Janne; Nilsson, Carl Gustaf

1998-01-01

Objectives: To assess whether the levonorgestrel intrauterine system could provide a conservative alternative to hysterectomy in the treatment of excessive uterine bleeding. Design: Open randomised multicentre study with two parallel groups: a levonorgestrel intrauterine system group and a control group. Setting: Gynaecology departments of three hospitals in Finland. Subjects: Fifty six women aged 33-49 years scheduled to undergo hysterectomy for treatment of excessive uterine bleeding. Interventions: Women were randomised either to continue with their current medical treatment or to have a levonorgestrel intrauterine system inserted. Main outcome measure: Proportion of women cancelling their decision to undergo hysterectomy. Results: At 6 months, 64.3% (95% confidence interval 44.1 to 81.4%) of the women in the levonorgestrel intrauterine system group and 14.3% (4.0 to 32.7%) in the control group had cancelled their decision to undergo hysterectomy (P<0.001). Conclusions: The use of the levonorgestrel intrauterine system is a good conservative alternative to hysterectomy in the treatment of menorrhagia and should be considered before hysterectomy or other invasive treatments. PMID:9552948

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

PubMed

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-07-17

Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

PubMed Central

Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

2017-01-01

Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0–10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results. PMID:28716797

Does cuff pressure monitoring reduce postoperative pharyngolaryngeal adverse events after LMA-ProSeal insertion? A parallel group randomised trial.

PubMed

Vasanth Karthik, R; Ranganathan, Priya; Kulkarni, Atul P; Sharma, Kailash S

2014-10-01

The incidence of postoperative pharyngolaryngeal complications after laryngeal mask airway (LMA) insertion can be as high as 50%. Over-inflation of the LMA cuff may be a causal factor. We conducted a single-centre parallel group randomised trial to determine whether maintaining LMA-ProSeal intra-cuff pressures below 60 cm H2O decreases postoperative pharyngolaryngeal complications. We recruited 120 adult patients who were scheduled to undergo elective surgery under general anaesthesia. Appropriate sized LMA-ProSeal was inserted and the cuff was inflated with air (to no more than the maximum recommended volume) until there was no audible leak. Patients were randomised to either the control group (n = 60), where the intra-cuff pressure was noted and no further action was taken, or to the pressure-monitored group (n = 60), where intra-cuff pressure was maintained below 60 cm H2O. Pharyngolaryngeal complications consisting of sore throat, dysphonia and dysphagia were assessed at 1, 2, and 24 h postoperatively. Patients, anaesthesiologists and assessors were blinded to group allocation. The primary outcome was a composite endpoint of any pharyngolaryngeal complication at any of the three time points. Secondary outcomes were the incidence of individual outcomes at each time point. The incidence of pharyngolaryngeal complications at any time point was 42% in the routine care group and 32% in the pressure-monitored group (95% CI for difference +28 to -7%, p = 0.26). There was no difference between groups for any of the secondary outcomes. Our study failed to demonstrate a statistically significant reduction in postoperative pharyngolaryngeal complications by limiting intra-cuff pressures in the LMA-Proseal.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

PubMed Central

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-01-01

Objective To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Methods Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity. Results AUCinf and Cmax were similar across the three groups. Geometrical mean ratio (GMR) of AUCinf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmax was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinf and Cmax were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Conclusions Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. Trial registration number EudraCT number 2012-000785-37; Results. PMID:27466231

Emollient bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness

PubMed Central

Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Rumsby, Kate; Chorozoglou, Maria; Becque, Taeko; Roberts, Amanda; Liddiard, Lyn; Nollett, Claire; Hooper, Julie; Prude, Martina; Wood, Wendy; Thomas, Kim S; Thomas-Jones, Emma; Williams, Hywel C; Little, Paul

2018-01-01

Abstract Objectives To determine the clinical effectiveness and cost effectiveness of including emollient bath additives in the management of eczema in children. Design Pragmatic randomised open label superiority trial with two parallel groups. Setting 96 general practices in Wales and western and southern England. Participants 483 children aged 1 to 11 years, fulfilling UK diagnostic criteria for atopic dermatitis. Children with very mild eczema and children who bathed less than once weekly were excluded. Interventions Participants in the intervention group were prescribed emollient bath additives by their usual clinical team to be used regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued with standard eczema management, including leave-on emollients, and caregivers were given standardised advice on how to wash participants. Main outcome measures The primary outcome was eczema control measured by the patient oriented eczema measure (POEM, scores 0-7 mild, 8-16 moderate, 17-28 severe) weekly for 16 weeks. Secondary outcomes were eczema severity over one year (monthly POEM score from baseline to 52 weeks), number of eczema exacerbations resulting in primary healthcare consultation, disease specific quality of life (dermatitis family impact), generic quality of life (child health utility-9D), utilisation of resources, and type and quantity of topical corticosteroid or topical calcineurin inhibitors prescribed. Results 483 children were randomised and one child was withdrawn, leaving 482 children in the trial: 51% were girls (244/482), 84% were of white ethnicity (447/470), and the mean age was 5 years. 96% (461/482) of participants completed at least one post-baseline POEM, so were included in the analysis, and 77% (370/482) completed questionnaires for more than 80% of the time points for the primary outcome (12/16 weekly questionnaires to 16 weeks). The mean baseline POEM score was 9.5 (SD 5.7) in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. The mean POEM score over the 16 week period was 7.5 (SD. 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group. No statistically significant difference was found in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additives group were 0.41 points higher than in the bath additives group (95% confidence interval −0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. The groups did not differ in secondary outcomes, economic outcomes, or adverse effects. Conclusions This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of eczema in children. Further research is needed into optimal regimens for leave-on emollient and soap substitutes. Trial registration Current Controlled Trials ISRCTN84102309. PMID:29724749

Emollient bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness.

PubMed

Santer, Miriam; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Rumsby, Kate; Chorozoglou, Maria; Becque, Taeko; Roberts, Amanda; Liddiard, Lyn; Nollett, Claire; Hooper, Julie; Prude, Martina; Wood, Wendy; Thomas, Kim S; Thomas-Jones, Emma; Williams, Hywel C; Little, Paul

2018-05-03

To determine the clinical effectiveness and cost effectiveness of including emollient bath additives in the management of eczema in children. Pragmatic randomised open label superiority trial with two parallel groups. 96 general practices in Wales and western and southern England. 483 children aged 1 to 11 years, fulfilling UK diagnostic criteria for atopic dermatitis. Children with very mild eczema and children who bathed less than once weekly were excluded. Participants in the intervention group were prescribed emollient bath additives by their usual clinical team to be used regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued with standard eczema management, including leave-on emollients, and caregivers were given standardised advice on how to wash participants. The primary outcome was eczema control measured by the patient oriented eczema measure (POEM, scores 0-7 mild, 8-16 moderate, 17-28 severe) weekly for 16 weeks. Secondary outcomes were eczema severity over one year (monthly POEM score from baseline to 52 weeks), number of eczema exacerbations resulting in primary healthcare consultation, disease specific quality of life (dermatitis family impact), generic quality of life (child health utility-9D), utilisation of resources, and type and quantity of topical corticosteroid or topical calcineurin inhibitors prescribed. 483 children were randomised and one child was withdrawn, leaving 482 children in the trial: 51% were girls (244/482), 84% were of white ethnicity (447/470), and the mean age was 5 years. 96% (461/482) of participants completed at least one post-baseline POEM, so were included in the analysis, and 77% (370/482) completed questionnaires for more than 80% of the time points for the primary outcome (12/16 weekly questionnaires to 16 weeks). The mean baseline POEM score was 9.5 (SD 5.7) in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. The mean POEM score over the 16 week period was 7.5 (SD. 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group. No statistically significant difference was found in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additives group were 0.41 points higher than in the bath additives group (95% confidence interval -0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. The groups did not differ in secondary outcomes, economic outcomes, or adverse effects. This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of eczema in children. Further research is needed into optimal regimens for leave-on emollient and soap substitutes. Current Controlled Trials ISRCTN84102309. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of an interactive text-messaging service on patient retention during the first year of HIV care in Kenya (WelTel Retain): an open-label, randomised parallel-group study.

PubMed

van der Kop, Mia Liisa; Muhula, Samuel; Nagide, Patrick I; Thabane, Lehana; Gelmon, Lawrence; Awiti, Patricia Opondo; Abunah, Bonface; Kyomuhangi, Lennie Bazira; Budd, Matthew A; Marra, Carlo; Patel, Anik; Karanja, Sarah; Ojakaa, David I; Mills, Edward J; Ekström, Anna Mia; Lester, Richard Todd

2018-03-01

Retention of patients in HIV care is crucial to ensure timely treatment initiation, viral suppression, and to avert AIDS-related deaths. We did a randomised trial to determine whether a text-messaging intervention improved retention during the first year of HIV care. This unmasked, randomised parallel-group study was done at two clinics in informal settlements in Nairobi, Kenya. Eligible participants were aged 18 years or older, HIV-positive, had their own mobile phone or access to one, and were able to use simple text messaging (or have somebody who could text message on their behalf). Participants were randomly assigned (1:1), with random block sizes of 2, 4, and 6, to the intervention or control group. Participants in the intervention group received a weekly text message from the automated WelTel service for 1 year and were asked to respond within 48 h. Participants in the control group did not receive text messages. Participants in both groups received usual care, which comprised psychosocial support and counselling; patient education; CD4 cell count; treatment; screening for tuberculosis, opportunistic infections, and sexually transmitted infections; prevention of mother-to-child transmission and family planning services; and up to two telephone calls for missed appointments. The primary outcome was retention in care at 12 months (ie, clinic attendance 10-14 months after the first visit). Participants who did not attend this 12-month appointment were traced, and we considered as retained those who were confirmed to be active in care elsewhere. The data analyst and clinic staff were masked to the group assignment, whereas participants and research nurses were not. We analysed the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01630304. Between April 4, 2013, and June 4, 2015, we screened 1068 individuals, of whom 700 were recruited. 349 people were allocated to the intervention group and 351 to the control group. Participants were followed up for a median of 55 weeks (IQR 51-60). At 12 months, 277 (79%) of 349 participants in the intervention group were retained, compared with 285 (81%) of 351 participants in the control group (risk ratio 0·98, 95% CI 0·91-1·05; p=0·54). There was one mild adverse event related to the intervention, a domestic dispute that occurred when a participant's partner became suspicious of the weekly messages and follow-up calls. This weekly text-messaging service did not improve retention of people in early HIV care. The intervention might have a modest role in improving self-perceived health-related quality of life in individuals in HIV care in similar settings. National Institutes of Health and Canadian Institutes of Health Research Canadian HIV Trials Network. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

PubMed

Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

2016-11-01

Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m 2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of 959 in the capecitabine and bevacizumab group) and diarrhoea (102 [11%] vs 104 [11%]), and, with the addition of bevacizumab, expected increases were recorded in all-grade hypertension (320 [33%] vs 75 [8%]), proteinuria (197 [21%] vs 49 [5%]), and wound healing problems (30 [3%] vs 17 [2%]). 571 serious adverse events were reported (221 with capecitabine alone and 350 with capecitabine and bevacizumab). Most of these were gastrointestinal (n=245) or cardiovascular (n=169). 23 deaths within 6 months of randomisation were classified as being related to treatment, eight in the capecitabine alone group and 15 in the capecitabine and bevacizumab group. The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used. Roche. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinico-radiological Outcome Analysis of Parallel Plating with Perpendicular Plating in Distal Humeral Intra-articular Fractures: Prospective Randomised Study

PubMed Central

Shekhawat, Vishal; Banshiwal, Ramesh Chandra; Verma, Rajender Kumar

2017-01-01

Introduction The distal humeral fractures are common fractures of upper limb and are difficult to treat. These fractures, if left untreated or inadequately treated, leads to poor outcomes. Management of distal humeral fractures are pertained to many controversies and one among them is position of plates. Aim To compare the clinical and radiological outcomes in patients with intra-articular distal humerus fractures, treated using parallel and perpendicular double plating methods. Materials and Methods A total of 38 patients with distal humerus fractures, 20 in perpendicular plating group (group A) and 18 in parallel plating group (group B), were included in this prospective randomised study. At each follow up patients were evaluated clinically and radiologically for union and the outcomes were measured in terms of Mayo Elbow Performance Score (MEPS) consisting of pain intensity, range of motion, stability and function. MEP score greater than 90 is considered as excellent; Score 75 to 89 is good; Score 60 to 74 is fair and Score less than 60 is poor. Results In our study, 15 patients (75%) in group A, and 13 patients (72.22%) in group B achieved excellent results. Two patients (10%) in group A and 4 patients (22.22%) in group B attained good results. Complications developed in 2 patients in each groups. No significant differences were found between the clinical outcomes of the two plating methods. Conclusion Neither of the plating techniques are superior to the other, as inferred from the insignificant differences in bony union, elbow function and complications between the two plating techniques. PMID:28384948

Clinico-radiological Outcome Analysis of Parallel Plating with Perpendicular Plating in Distal Humeral Intra-articular Fractures: Prospective Randomised Study.

PubMed

Govindasamy, Ramachandran; Shekhawat, Vishal; Banshiwal, Ramesh Chandra; Verma, Rajender Kumar

2017-02-01

The distal humeral fractures are common fractures of upper limb and are difficult to treat. These fractures, if left untreated or inadequately treated, leads to poor outcomes. Management of distal humeral fractures are pertained to many controversies and one among them is position of plates. To compare the clinical and radiological outcomes in patients with intra-articular distal humerus fractures, treated using parallel and perpendicular double plating methods. A total of 38 patients with distal humerus fractures, 20 in perpendicular plating group (group A) and 18 in parallel plating group (group B), were included in this prospective randomised study. At each follow up patients were evaluated clinically and radiologically for union and the outcomes were measured in terms of Mayo Elbow Performance Score (MEPS) consisting of pain intensity, range of motion, stability and function. MEP score greater than 90 is considered as excellent; Score 75 to 89 is good; Score 60 to 74 is fair and Score less than 60 is poor. In our study, 15 patients (75%) in group A, and 13 patients (72.22%) in group B achieved excellent results. Two patients (10%) in group A and 4 patients (22.22%) in group B attained good results. Complications developed in 2 patients in each groups. No significant differences were found between the clinical outcomes of the two plating methods. Neither of the plating techniques are superior to the other, as inferred from the insignificant differences in bony union, elbow function and complications between the two plating techniques.

13C metabolic flux analysis: optimal design of isotopic labeling experiments.

PubMed

Antoniewicz, Maciek R

2013-12-01

Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Parallel-multiplexed excitation light-sheet microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Dongli; Zhou, Weibin; Peng, Leilei

2017-02-01

Laser scanning light-sheet imaging allows fast 3D image of live samples with minimal bleach and photo-toxicity. Existing light-sheet techniques have very limited capability in multi-label imaging. Hyper-spectral imaging is needed to unmix commonly used fluorescent proteins with large spectral overlaps. However, the challenge is how to perform hyper-spectral imaging without sacrificing the image speed, so that dynamic and complex events can be captured live. We report wavelength-encoded structured illumination light sheet imaging (λ-SIM light-sheet), a novel light-sheet technique that is capable of parallel multiplexing in multiple excitation-emission spectral channels. λ-SIM light-sheet captures images of all possible excitation-emission channels in true parallel. It does not require compromising the imaging speed and is capable of distinguish labels by both excitation and emission spectral properties, which facilitates unmixing fluorescent labels with overlapping spectral peaks and will allow more labels being used together. We build a hyper-spectral light-sheet microscope that combined λ-SIM with an extended field of view through Bessel beam illumination. The system has a 250-micron-wide field of view and confocal level resolution. The microscope, equipped with multiple laser lines and an unlimited number of spectral channels, can potentially image up to 6 commonly used fluorescent proteins from blue to red. Results from in vivo imaging of live zebrafish embryos expressing various genetic markers and sensors will be shown. Hyper-spectral images from λ-SIM light-sheet will allow multiplexed and dynamic functional imaging in live tissue and animals.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

PubMed

Bath, Philip M; Woodhouse, Lisa J; Appleton, Jason P; Beridze, Maia; Christensen, Hanne; Dineen, Robert A; Duley, Lelia; England, Timothy J; Flaherty, Katie; Havard, Diane; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, Hugh S; Montgomery, Alan A; Pocock, Stuart J; Randall, Marc; Ranta, Annemarei; Robinson, Thompson G; Scutt, Polly; Venables, Graham S; Sprigg, Nikola

2018-03-03

Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001). Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

PubMed

Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

2016-02-20

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (p<0·0001) for patients treated with ibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87%) patients, and fewer discontinuations of study medication due to adverse events for ibrutinib versus temsirolimus (9 [6%] vs 36 [26%]). Ibrutinib treatment resulted in significant improvement in progression-free survival and better tolerability versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma. These data lend further support to the positive benefit-risk ratio for ibrutinib in relapsed or refractory mantle-cell lymphoma. Janssen Research & Development, LLC. Copyright © 2016 Elsevier Ltd. All rights reserved.

The HubBLe trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for haemorrhoids.

PubMed

Tiernan, Jim; Hind, Daniel; Watson, Angus; Wailoo, Allan J; Bradburn, Michael; Shephard, Neil; Biggs, Katie; Brown, Steven

2012-10-25

Haemorrhoids (piles) are a very common condition seen in surgical clinics. After exclusion of more sinister causes of haemorrhoidal symptoms (rectal bleeding, perianal irritation and prolapse), the best option for treatment depends upon persistence and severity of the symptoms. Minor symptoms often respond to conservative treatment such as dietary fibre and reassurance. For more severe symptoms treatment such as rubber band ligation may be therapeutic and is a very commonly performed procedure in the surgical outpatient setting. Surgery is usually reserved for those who have more severe symptoms, as well as those who do not respond to non-operative therapy; surgical techniques include haemorrhoidectomy and haemorrhoidopexy. More recently, haemorrhoidal artery ligation has been introduced as a minimally invasive, non destructive surgical option.There are substantial data in the literature concerning efficacy and safety of 'rubber band ligation including multiple comparisons with other interventions, though there are no studies comparing it to haemorrhoidal artery ligation. A recent overview has been carried out by the National Institute for Health and Clinical Excellence which concludes that current evidence shows haemorrhoidal artery ligation to be a safe alternative to haemorrhoidectomy and haemorrhoidopexy though it also highlights the lack of good quality data as evidence for the advantages of the technique. The aim of this study is to establish the clinical effectiveness and cost effectiveness of haemorrhoidal artery ligation compared with conventional rubber band ligation in the treatment of people with symptomatic second or third degree (Grade II or Grade III) haemorrhoids. A multi-centre, parallel group randomised controlled trial. The primary outcome is patient-reported symptom recurrence twelve months following the intervention. Secondary outcome measures relate to symptoms, complications, health resource use, health related quality of life and cost effectiveness following the intervention. 350 patients with grade II or grade III haemorrhoids will be recruited in surgical departments in up to 14 NHS hospitals. A multi-centre, parallel group randomised controlled trial. Block randomisation by centre will be used, with 175 participants randomised to each group. The results of the research will help inform future practice for the treatment of grade II and III haemorrhoids. ISRCTN41394716.

Combining behavioural activation with physical activity promotion for adults with depression: findings of a parallel-group pilot randomised controlled trial (BAcPAc).

PubMed

Pentecost, Claire; Farrand, Paul; Greaves, Colin J; Taylor, Rod S; Warren, Fiona C; Hillsdon, Melvyn; Green, Colin; Welsman, Jo R; Rayson, Kat; Evans, Philip H; Taylor, Adrian H

2015-08-20

Depression is associated with physical inactivity, which may mediate the relationship between depression and a range of chronic physical health conditions. However, few interventions have combined a psychological intervention for depression with behaviour change techniques, such as behavioural activation (BA), to promote increased physical activity. To determine procedural and clinical uncertainties to inform a definitive randomised controlled trial (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to Psychological Therapies (IAPT) services in South West England. We aimed to recruit 80 adults with depression and randomise them to a supported, written self-help programme based on either BA or BA plus physical activity promotion (BAcPAc). Data were collected at baseline and 4 months post-randomisation to evaluate trial retention, intervention uptake and variance in outcomes to inform a sample size calculation. Qualitative data were collected from participants and psychological wellbeing practitioners (PWPs) to assess the acceptability and feasibility of the trial methods and the intervention. Routine data were collected to evaluate resource use and cost. Sixty people with depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer physical activity data were collected for 64 % of those followed. Twenty participants (33 %) attended at least one treatment appointment. Interview data were analysed for 15 participants and 9 study PWPs. The study highlighted the challenges of conducting an RCT within existing IAPT services with high staff turnover and absences, participant scheduling issues, PWP and participant preferences for cognitive focussed treatment, and deviations from BA delivery protocols. The BAcPAc intervention was generally acceptable to patients and PWPs. Although recruitment procedures and data collection were challenging, participants generally engaged with the BAcPAc self-help booklets and reported willingness to increase their physical activity. A number of feasibility issues were identified, in particular the under-use of BA as a treatment for depression, the difficulty that PWPs had in adapting their existing procedures for study purposes and the instability of the IAPT PWP workforce. These problems would need to be better understood and resolved before proceeding to a full-scale RCT. ISRCTN74390532 . Registered on 26 March 2013.

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis

PubMed Central

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-01-01

Introduction Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Methods Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. Ethics and dissemination A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. Trial registration number NCT023528702; Pre-results. PMID:27072573

Improving distress in dialysis (iDiD): a feasibility two-arm parallel randomised controlled trial of an online cognitive behavioural therapy intervention with and without therapist-led telephone support for psychological distress in patients undergoing haemodialysis.

PubMed

Hudson, Joanna L; Moss-Morris, Rona; Game, David; Carroll, Amy; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2016-04-12

Psychological distress is common in end-stage kidney disease (ESKD) and is associated with poorer health outcomes. Cognitive behavioural therapy (CBT) is recommended in UK clinical guidelines for the management of depression in people with long-term conditions. Access to skilled therapists competent in managing the competing mental and physical health demands of ESKD is limited. Online CBT treatments tailored to the needs of the ESKD population offers a pragmatic solution for under-resourced services. This study examines the feasibility and acceptability of implementing a two-arm parallel randomised controlled trial of online CBT with (intervention arm) and without (control arm) therapist support to improve psychological distress in patients undergoing haemodialysis. Patients will be screened for depression and anxiety while attending for their haemodialysis treatments. We aim to recruit 60 adult patients undergoing haemodialysis who meet criteria for mild to moderately severe symptoms of depression and/or anxiety. Patients will be randomised individually (using a 1:1 computerised sequence ratio) to either online CBT with therapist telephone support (intervention arm), or online CBT with no therapist (control arm). Outcomes include feasibility and acceptability descriptive data on rates of recruitment, randomisation, retention and treatment adherence. Self-report outcomes include measures of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), quality of life (Euro-QoL), service use (client service receipt inventory) and illness cognitions (brief illness perception questionnaire). A qualitative process evaluation will also be conducted. The statistician will be blinded to treatment allocation. A National Health Service (NHS) research ethics committee approved the study. Data from this study will provide essential information for the design and testing of further interventions to ameliorate distress in patients undergoing dialysis. Any amendments to the protocol will be submitted to the NHS committee and study sponsor. NCT023528702; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Recruitment, adherence, and retention of endometrial cancer survivors in a behavioural lifestyle programme: the Diet and Exercise in Uterine Cancer Survivors (DEUS) parallel randomised pilot trial.

PubMed

Koutoukidis, Dimitrios A; Beeken, Rebecca J; Manchanda, Ranjit; Michalopoulou, Moscho; Burnell, Matthew; Knobf, M Tish; Lanceley, Anne

2017-10-08

Healthy eating and physical activity may help endometrial cancer survivors (ECS) improve their quality of life. However, most ECS do not meet the relevant guidelines. This pilot trial aimed to test the study feasibility procedures for a definitive trial of a behavioural lifestyle programme. This 24-week parallel two-arm randomised pilot trial took place in two hospitals in London, UK (April 2015-June 2016). Sixty disease-free ECS within 3 years of diagnosis. Participants were randomised using minimisation to receive the intervention or care as usual. The 'Shape-Up following cancer treatment' programme used self-monitoring, goal-setting, self-incentives, problem-solving and group social support for 12 hours over 8 weeks to help survivors improve their eating and physical activity. The main outcome measures were recruitment, adherence, and retention rates. Further outcomes included barriers to participation and feedback on programme satisfaction. Of the 296 potentially eligible ECS, 20% (n=60) were randomly allocated to the active intervention (n=29) or control group (n=31). Three participants in each arm were deemed ineligible after randomisation and excluded from analysis. Twenty participants (77%; 95% CI 61% to 93%) adhered to the intervention and provided generally favourable feedback. At 24 weeks, 25/26 (96%; 95% CI 89% to 100%) intervention and 24/28 (86%; 95% CI 73% to 99%) control participants completed their assessment. No intervention-related adverse events were reported. Among eligible survivors who declined study participation (n=83), inconvenience (78%; 95% CI 69% to 87%) was the most common barrier. The trial was feasible to deliver based on the a priori feasibility criteria. Enhancing recruitment and adherence in a definitive trial will require designs that promote convenience and consider ECS-reported barriers. NCT02433080; Pre-results. University College London, St. Bartholomew's Hospital Nurses League, and NIHR University College London Hospitals Biomedical Research Centre. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Screening uptake rates and the clinical and cost effectiveness of screening for gestational diabetes mellitus in primary versus secondary care: study protocol for a randomised controlled trial

PubMed Central

2014-01-01

Background The risks associated with gestational diabetes mellitus (GDM) are well recognized, and there is increasing evidence to support treatment of the condition. However, clear guidance on the ideal approach to screening for GDM is lacking. Professional groups continue to debate whether selective screening (based on risk factors) or universal screening is the most appropriate approach. Additionally, there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment. Furthermore, the implications of possible screening options on health care costs are not well established. In response to this uncertainty there have been repeated calls for well-designed, randomised trials to determine the efficacy of screening, diagnosis, and management plans for GDM. We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings. Methods/Design This will be an unblinded, two-group, parallel randomised controlled trial (RCT). The target population includes 784 women presenting for their first antenatal visit at 12 to 18 weeks gestation at two hospitals in the west of Ireland: Galway University Hospital and Mayo General Hospital. Participants will be offered universal screening for GDM at 24 to 28 weeks gestation in either primary care (n = 392) or secondary care (n = 392) locations. The primary outcome variable is the uptake rate of screening. Secondary outcomes include indicators of clinical effectiveness of screening at each screening site (primary and secondary) including gestational week at time of screening, time to access antenatal diabetes services for women diagnosed with GDM, and pregnancy and neonatal outcomes for women with GDM. In addition, parallel economic and qualitative evaluations will be conducted. The trial will cover the period from the woman’s first hospital antenatal visit at 12 to 18 weeks gestation, until the completion of the pregnancy. Trial registration Current Controlled Trials: ISRCTN02232125 PMID:24438478

PC6 acupoint stimulation for the prevention of postcardiac surgery nausea and vomiting: a protocol for a two-group, parallel, superiority randomised clinical trial.

PubMed

Cooke, Marie; Rickard, Claire; Rapchuk, Ivan; Shekar, Kiran; Marshall, Andrea P; Comans, Tracy; Doi, Suhail; McDonald, John; Spooner, Amy

2014-11-13

Postoperative nausea and vomiting (PONV) are frequent but unwanted complications for patients following anaesthesia and cardiac surgery, affecting at least a third of patients, despite pharmacological treatment. The primary aim of the proposed research is to test the efficacy of PC6 acupoint stimulation versus placebo for reducing PONV in cardiac surgery patients. In conjunction with this we aim to develop an understanding of intervention fidelity and factors that support, or impede, the use of PC6 acupoint stimulation, a knowledge translation approach. 712 postcardiac surgery participants will be recruited to take part in a two-group, parallel, superiority, randomised controlled trial. Participants will be randomised to receive a wrist band on each wrist providing acupressure to PC six using acupoint stimulation or a placebo. Randomisation will be computer generated, use randomly varied block sizes, and be concealed prior to the enrolment of each patient. The wristbands will remain in place for 36 h. PONV will be evaluated by the assessment of both nausea and vomiting, use of rescue antiemetics, quality of recovery and cost. Patient satisfaction with PONV care will be measured and clinical staff interviewed about the clinical use, feasibility, acceptability and challenges of using acupressure wristbands for PONV. Ethics approval will be sought from appropriate Human Research Ethics Committee/s before start of the study. A systematic review of the use of wrist acupressure for PC6 acupoint stimulation reported minor side effects only. Study progress will be reviewed by a Data Safety Monitoring Committee (DSMC) for nausea and vomiting outcomes at n=350. Dissemination of results will include conference presentations at national and international scientific meetings and publications in peer-reviewed journals. Study participants will receive a one-page lay-summary of results. Australian New Zealand Clinical Trials Registry--ACTRN12614000589684. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Quick and Parallel Analytical Method Based on Quantum Dots Labeling for ToRCH-Related Antibodies

NASA Astrophysics Data System (ADS)

Yang, Hao; Guo, Qing; He, Rong; Li, Ding; Zhang, Xueqing; Bao, Chenchen; Hu, Hengyao; Cui, Daxiang

2009-12-01

Quantum dot is a special kind of nanomaterial composed of periodic groups of II-VI, III-V or IV-VI materials. Their high quantum yield, broad absorption with narrow photoluminescence spectra and high resistance to photobleaching, make them become a promising labeling substance in biological analysis. Here, we report a quick and parallel analytical method based on quantum dots for ToRCH-related antibodies including Toxoplasma gondii, Rubella virus, Cytomegalovirus and Herpes simplex virus type 1 (HSV1) and 2 (HSV2). Firstly, we fabricated the microarrays with the five kinds of ToRCH-related antigens and used CdTe quantum dots to label secondary antibody and then analyzed 100 specimens of randomly selected clinical sera from obstetric outpatients. The currently prevalent enzyme-linked immunosorbent assay (ELISA) kits were considered as “golden standard” for comparison. The results show that the quantum dots labeling-based ToRCH microarrays have comparable sensitivity and specificity with ELISA. Besides, the microarrays hold distinct advantages over ELISA test format in detection time, cost, operation and signal stability. Validated by the clinical assay, our quantum dots-based ToRCH microarrays have great potential in the detection of ToRCH-related pathogens.

SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation.

PubMed

Williams, Annabelle E; Croft, Julie; Napp, Vicky; Corrigan, Neil; Brown, Julia M; Hulme, Claire; Brown, Steven R; Lodge, Jen; Protheroe, David; Jayne, David G

2016-02-01

Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18 months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.

A label-free electrochemical sensor for detection of mercury(II) ions based on the direct growth of guanine nanowire.

PubMed

Huang, Yan Li; Gao, Zhong Feng; Jia, Jing; Luo, Hong Qun; Li, Nian Bing

2016-05-05

A simple, sensitive and label-free electrochemical sensor is developed for detection of Hg(2+) based on the strong and stable T-Hg(2+)-T mismatches. In the presence of Mg(2+), the parallel G-quadruplex structures could be specifically recognized and precipitated in parallel conformation. Therefore, the guanine nanowire was generated on the electrode surface, triggering the electrochemical H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). In this research, a new method of signal amplification for the quantitative detection of Hg(2+) was described based on the direct growth of guanine nanowire via guanine nanowire. Under optimum conditions, Hg(2+) was detected in the range of 100 pM-100 nM, and the detection limit is 33 pM. Compared to the traditional single G-quadruplex label unit, this electrochemical sensor showed high sensitivity and selectivity for detecting Hg(2+). Copyright © 2016 Elsevier B.V. All rights reserved.

Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome.

PubMed

Fodor, Anthony A; Pimentel, Mark; Chey, William D; Lembo, Anthony; Golden, Pamela L; Israel, Robert J; Carroll, Ian M

2018-04-30

Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D. ClinicalTrials.gov identifier number: NCT01543178.

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX)

PubMed Central

Cotton, S C; Boachie, C; Ramsay, C R; Krukowski, Z H; Heading, R C; Campbell, M K

2013-01-01

Objectives To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). Setting Initial recruitment in 21 UK hospitals. Participants Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. Intervention The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. Main outcome measures Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. Results By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations—most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. Conclusions After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. Trial registration Current Controlled Trials ISRCTN15517081. PMID:23599318

PANSAID-PAracetamol and NSAID in combination: detailed statistical analysis plan for a randomised, blinded, parallel, four-group multicentre clinical trial.

PubMed

Thybo, Kasper Højgaard; Jakobsen, Janus Christian; Hägi-Pedersen, Daniel; Pedersen, Niels Anker; Dahl, Jørgen Berg; Schrøder, Henrik Morville; Bülow, Hans Henrik; Bjørck, Jan Gottfrid; Overgaard, Søren; Mathiesen, Ole; Wetterslev, Jørn

2017-10-10

Effective postoperative pain management is essential for the rehabilitation of the surgical patient. The PANSAID trial evaluates the analgesic effects and safety of the combination of paracetamol and ibuprofen. This paper describes in detail the statistical analysis plan for the primary publication to prevent outcome reporting bias and data-driven analysis results. The PANSAID trial is a multicentre, randomised, controlled, parallel, four-group clinical trial comparing the beneficial and harmful effects of different doses and combinations of paracetamol and ibuprofen in patients having total hip arthroplastic surgery. Patients, caregivers, physicians, investigators, and statisticians are blinded to the intervention. The two co-primary outcomes are 24-h consumption of morphine and proportion of patients with one or more serious adverse events within 90 days after surgery. Secondary outcomes are pain scores during mobilisation and at rest at 6 and 24 h postoperatively, and the proportion of patients with one or more adverse events within 24 h postoperatively. PANSAID will provide a large trial with low risk of bias regarding benefits and harms of the combination of paracetamol and ibuprofen used in a perioperative setting. ClinicalTrials.org identifier: NCT02571361 . Registered on 7 October 2015.

Intermittent catheterisation with hydrophilic-coated catheters (SpeediCath) reduces the risk of clinical urinary tract infection in spinal cord injured patients: a prospective randomised parallel comparative trial.

PubMed

De Ridder, D J M K; Everaert, K; Fernández, L García; Valero, J V Forner; Durán, A Borau; Abrisqueta, M L Jauregui; Ventura, M G; Sotillo, A Rodriguez

2005-12-01

To compare the performance of SpeediCath hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters, in traumatic spinal cord injured patients presenting with functional neurogenic bladder-sphincter disorders. A 1-year, prospective, open, parallel, comparative, randomised, multi centre study included 123 male patients, > or =16 y and injured within the last 6 months. Primary endpoints were occurrence of symptomatic urinary tract infection (UTI) and hematuria. Secondary endpoints were development of urethral strictures and convenience of use. The main hypothesis was that coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria. 57 out of 123 patients completed the 12-month study. Fewer patients using the SpeediCath hydrophilic-coated catheter (64%) experienced 1 or more UTIs compared to the uncoated PVC catheter group (82%) (p = 0.02). Thus, twice as many patients in the SpeediCath group were free of UTI. There was no significant difference in the number of patients experiencing bleeding episodes (38/55 SpeediCath; 32/59 PVC) and no overall difference in the occurrence of hematuria, leukocyturia and bacteriuria. The results indicate that there is a beneficial effect regarding UTI when using hydrophilic-coated catheters.

Parallel State Space Construction for a Model Checking Based on Maximality Semantics

NASA Astrophysics Data System (ADS)

El Abidine Bouneb, Zine; Saīdouni, Djamel Eddine

2009-03-01

The main limiting factor of the model checker integrated in the concurrency verification environment FOCOVE [1, 2], which use the maximality based labeled transition system (noted MLTS) as a true concurrency model[3, 4], is currently the amount of available physical memory. Many techniques have been developed to reduce the size of a state space. An interesting technique among them is the alpha equivalence reduction. Distributed memory execution environment offers yet another choice. The main contribution of the paper is to show that the parallel state space construction algorithm proposed in [5], which is based on interleaving semantics using LTS as semantic model, may be adapted easily to the distributed implementation of the alpha equivalence reduction for the maximality based labeled transition systems.

Cognitive bias modification for social anxiety in adults who stutter: a feasibility study of a randomised controlled trial

PubMed Central

Gascoine, Sally; Carroll, Amy; Humby, Kate; Kingston, Mary; Shepstone, Lee; Risebro, Helen; Mackintosh, Bundy; Thompson, Tammy Davidson; Hodgekins, Jo

2017-01-01

Objective To determine the feasibility and acceptability of a computerised treatment for social anxiety disorder for adults who stutter including identification of recruitment, retention and completion rates, large cost drivers and selection of most appropriate outcome measure(s) to inform the design of a future definitive trial. Design Two-group parallel design (treatment vs placebo), double-blinded feasibility study. Participants: 31 adults who stutter. Intervention Attention training via an online probe detection task in which the stimuli were images of faces displaying neutral and disgusted expressions. Main outcome measures Psychological measures: Structured Clinical Interview Global Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic evaluation: resource use questionnaire; EuroQol three-dimension questionnaire. Acceptability: Likert Scale questionnaire of experience of trial, acceptability of the intervention and randomisation procedure. Results Feasibility of recruitment strategy was demonstrated. Participant feedback indicated that the intervention and definitive trial, including randomisation, would be acceptable to adults who stutter. Of the 31 participants who were randomised, 25 provided data at all three data collection points. Conclusions The feasibility study informed components of the intervention. Modifications to the design are needed before a definitive trial can be undertaken. Trial registration number I SRCTN55065978; Post-results. PMID:29061602

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study

PubMed Central

Radcliffe, Michael J; Lewith, George T; Turner, Richard G; Prescott, Philip; Church, Martin K; Holgate, Stephen T

2003-01-01

Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. Design Double blind randomised placebo controlled parallel group study. Setting Hospital in Hampshire. Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. Interventions Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of β glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. Main outcome measures Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. Results The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study. PMID:12896934

Haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids (HubBLe): a multicentre, open-label, randomised controlled trial.

PubMed

Brown, Steven R; Tiernan, James P; Watson, Angus J M; Biggs, Katie; Shephard, Neil; Wailoo, Allan J; Bradburn, Mike; Alshreef, Abualbishr; Hind, Daniel

2016-07-23

Optimum surgical intervention for low-grade haemorrhoids is unknown. Haemorrhoidal artery ligation (HAL) has been proposed as an efficacious, safe therapy while rubber band ligation (RBL) is a commonly used outpatient treatment. We compared recurrence after HAL versus RBL in patients with grade II-III haemorrhoids. This multicentre, open-label, parallel group, randomised controlled trial included patients from 17 acute UK NHS trusts. We screened patients aged 18 years or older presenting with grade II-III haemorrhoids. We excluded patients who had previously received any haemorrhoid surgery, more than one injection treatment for haemorrhoids, or more than one RBL procedure within 3 years before recruitment. Eligible patients were randomly assigned (in a 1:1 ratio) to either RBL or HAL with Doppler. Randomisation was computer-generated and stratified by centre with blocks of random sizes. Allocation concealment was achieved using a web-based system. The study was open-label with no masking of participants, clinicians, or research staff. The primary outcome was recurrence at 1 year, derived from the patient's self-reported assessment in combination with resource use from their general practitioner and hospital records. Recurrence was analysed in patients who had undergone one of the interventions and been followed up for at least 1 year. This study is registered with the ISRCTN registry, ISRCTN41394716. From Sept 9, 2012, to May 6, 2014, of 969 patients screened, 185 were randomly assigned to the HAL group and 187 to the RBL group. Of these participants, 337 had primary outcome data (176 in the RBL group and 161 in the HAL group). At 1 year post-procedure, 87 (49%) of 176 patients in the RBL group and 48 (30%) of 161 patients in the HAL group had haemorrhoid recurrence (adjusted odds ratio [aOR] 2·23, 95% CI 1·42-3·51; p=0·0005). The main reason for this difference was the number of extra procedures required to achieve improvement (57 [32%] participants in the RBL group and 23 [14%] participants in the HAL group had a subsequent procedure for haemorrhoids). The mean pain 1 day after procedure was 3·4 (SD 2·8) in the RBL group and 4·6 (2·8) in the HAL group (difference -1·2, 95% CI -1·8 to -0·5; p=0·0002); at day 7 the scores were 1·6 (2·3) in the RBL group and 3·1 (2·4) in the HAL group (difference -1·5, -2·0 to -1·0; p<0·0001). Pain scores did not differ between groups at 21 days and 6 weeks. 15 individuals reported serious adverse events requiring hospital admission. One patient in the RBL group had a pre-existing rectal tumour. Of the remaining 14 serious adverse events, 12 (7%) were among participants treated with HAL and two (1%) were in those treated with RBL. Six patients had pain (one treated with RBL, five treated with HAL), three had bleeding not requiring transfusion (one treated with RBL, two treated with HAL), two in the HAL group had urinary retention, two in the HAL group had vasovagal upset, and one in the HAL group had possible sepsis (treated with antibiotics). Although recurrence after HAL was lower than a single RBL, HAL was more painful than RBL. The difference in recurrence was due to the need for repeat bandings in the RBL group. Patients (and health commissioners) might prefer such a course of RBL to the more invasive HAL. NIHR Health Technology Assessment programme. Copyright © 2016 Brown et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Influence of the disease label 'polycystic ovary syndrome' on intention to have an ultrasound and psychosocial outcomes: a randomised online study in young women.

PubMed

Copp, Tessa; McCaffery, Kirsten; Azizi, Lamiae; Doust, Jenny; Mol, Ben W J; Jansen, Jesse

2017-04-01

Does the disease label 'polycystic ovary syndrome' (PCOS) have an impact on desire for medical testing and psychosocial outcomes? When given the disease label PCOS in a hypothetical scenario, participants had higher intention to have an ultrasound, perceived the condition to be more severe and had lower self-esteem than those not given the disease label. Widening diagnostic criteria and improved imaging sensitivity have increased the number of reproductive-aged women diagnosed with PCOS from 4% to 8% to up to 21%. The uncertain clinical benefit of knowing this diagnosis needs to be weighed against the potential for poor psychological outcomes in women labelled with PCOS. This experimental online study randomised 181 young women to receive one of four hypothetical scenarios of a doctor's visit in a 2 (PCOS disease label versus no disease label) x 2 (information about unreliability of ultrasounds in clarifying diagnosis versus no information) design. Participants were university students (mean age: 19.4). After presenting the scenario, intention to have an ultrasound, negative affect, self-esteem, perceived severity of condition, credibility of the doctor and interest in a second opinion were measured. Participants were then presented with a second scenario, where the possibility of PCOS overdiagnosis was mentioned. Change in intention and perceived severity were then measured. Participants given the PCOS label had significantly higher intention to have an ultrasound (mean = 6.62 versus mean = 5.76, P = 0.033, 95% CI(difference) = 0.069-1.599), perceived the condition to be more severe (17.17 versus 15.82, P = 0.019, 95% CI(difference) = 0.229-2.479) and had lower self-esteem (25.86 versus 27.56, P = 0.031, 95% CI(difference) = -3.187 to -0.157). After receiving overdiagnosis information, both intention and perceived severity decreased, regardless of condition (both P < 0.001). This study used hypothetical scenarios; it is likely that for women facing a real diagnosis of PCOS, outcomes would be more affected than in the current study. The hypothetical design, however, allowed the symptoms and risks of PCOS to be held constant across conditions, the impact on intention and psychosocial outcomes directly attributable to the effect of the disease label. These findings demonstrate the potential negative consequences of PCOS labelling. It is crucial we consider the impact of the label before diagnosing more women with PCOS when clinical benefit of this diagnosis is uncertain. This paper was written with support from a NHMRC grant awarded to the Screening and Test Evaluation Program. J.J. is supported by an NHMRC Early Career Fellowship. K.M. is supported by an NHMRC Career Development Fellowship. The authors declare that no competing interests exist. ACTRN12617000111370. 20/01/2017. 01/06/2015. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effectiveness of recruitment to a smartphone-delivered nutrition intervention in New Zealand: analysis of a randomised controlled trial

PubMed Central

Volkova, Ekaterina; Michie, Jo; Corrigan, Callie; Sundborn, Gerhard; Eyles, Helen; Jiang, Yannan; Mhurchu, Cliona Ni

2017-01-01

Objectives Delivery of interventions via smartphone is a relatively new initiative in public health, and limited evidence exists regarding optimal strategies for recruitment. We describe the effectiveness of approaches used to recruit participants to a smartphone-enabled nutrition intervention trial. Methods Internet and social media advertising, mainstream media advertising and research team networks were used to recruit New Zealand adults to a fully automated smartphone-delivered nutrition labelling trial (no face-to-face visits were required). Recruitment of Māori and Pacific participants was a key focus and ethically relevant recruitment materials and approaches were used where possible. The effectiveness of recruitment strategies was evaluated using Google Analytics, monitoring of study website registrations and randomisations, and self-reported participant data. The cost of the various strategies and associations with participant demographics were assessed. Results Over a period of 13 months, there were 2448 registrations on the study website, and 1357 eligible individuals were randomised into the study (55%). Facebook campaigns were the most successful recruitment strategy overall (43% of all randomised participants) and for all ethnic groups (Māori 44%, Pacific 44% and other 43%). Significant associations were observed between recruitment strategy and age (p<0.001), household size (p<0.001), ethnicity (p<0.001), gender (p=0.005) and interest in healthy eating (p=0.022). Facebook campaigns resulted in the highest absolute numbers of study registrations and randomisations (966 and 584, respectively). Network strategies and Facebook campaigns cost least per randomised participant (NZ$4 and NZ$5, respectively), whereas radio advertising costs most (NZ$179 per participant). Conclusion Internet and social media advertising were the most effective and least costly approaches to recruiting participants to a smartphone-delivered trial. These approaches also reached diverse ethnic groups. However, more culturally appropriate recruitment strategies are likely to be necessary in studies where large numbers of participants from specific ethnic groups are sought. Trial registration ACTRN12614000644662; Post-results. PMID:28674144

Effect of training and lifting equipment for preventing back pain in lifting and handling: systematic review

PubMed Central

2008-01-01

Objectives To determine whether advice and training on working techniques and lifting equipment prevent back pain in jobs that involve heavy lifting. Data sources Medline, Embase, CENTRAL, Cochrane Back Group’s specialised register, CINAHL, Nioshtic, CISdoc, Science Citation Index, and PsychLIT were searched up to September-November 2005. Review methods The primary search focused on randomised controlled trials and the secondary search on cohort studies with a concurrent control group. Interventions aimed to modify techniques for lifting and handling heavy objects or patients and including measurements for back pain, consequent disability, or sick leave as the main outcome were considered for the review. Two authors independently assessed eligibility of the studies and methodological quality of those included. For data synthesis, we summarised the results of studies comparing similar interventions. We used odds ratios and effect sizes to combine the results in a meta-analysis. Finally, we compared the conclusions of the primary and secondary analyses. Results Six randomised trials and five cohort studies met the inclusion criteria. Two randomised trials and all cohort studies were labelled as high quality. Eight studies looked at lifting and moving patients, and three studies were conducted among baggage handlers or postal workers. Those in control groups received no intervention or minimal training, physical exercise, or use of back belts. None of the comparisons in randomised trials (17 720 participants) yielded significant differences. In the secondary analysis, none of the cohort studies (772 participants) had significant results, which supports the results of the randomised trials. Conclusions There is no evidence to support use of advice or training in working techniques with or without lifting equipment for preventing back pain or consequent disability. The findings challenge current widespread practice of advising workers on correct lifting technique. PMID:18244957

Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial.

PubMed

Maritati, Federica; Alberici, Federico; Oliva, Elena; Urban, Maria L; Palmisano, Alessandra; Santarsia, Francesca; Andrulli, Simeone; Pavone, Laura; Pesci, Alberto; Grasselli, Chiara; Santi, Rosaria; Tumiati, Bruno; Manenti, Lucio; Buzio, Carlo; Vaglio, Augusto

2017-01-01

The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. MTX may be effective and safe for remission-maintenance in AAV. clinicaltrials.gov NCT00751517.

Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.

PubMed

Colleoni, Marco; Luo, Weixiu; Karlsson, Per; Chirgwin, Jacquie; Aebi, Stefan; Jerusalem, Guy; Neven, Patrick; Hitre, Erika; Graas, Marie-Pascale; Simoncini, Edda; Kamby, Claus; Thompson, Alastair; Loibl, Sibylle; Gavilá, Joaquín; Kuroi, Katsumasa; Marth, Christian; Müller, Bettina; O'Reilly, Seamus; Di Lauro, Vincenzo; Gombos, Andrea; Ruhstaller, Thomas; Burstein, Harold; Ribi, Karin; Bernhard, Jürg; Viale, Giuseppe; Maibach, Rudolf; Rabaglio-Poretti, Manuela; Gelber, Richard D; Coates, Alan S; Di Leo, Angelo; Regan, Meredith M; Goldhirsch, Aron

2018-01-01

In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women. We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing. Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group). In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them. Novartis and the International Breast Cancer Study Group. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of motivational interviewing on glycaemic control and perceived competence of diabetes self-management in patients with type 1 and type 2 diabetes mellitus after attending a group education programme: a randomised controlled trial.

PubMed

Rosenbek Minet, L K; Wagner, L; Lønvig, E M; Hjelmborg, J; Henriksen, J E

2011-07-01

The aim of this study was to measure the efficacy of motivational interviewing (MI) compared with usual care on changes in glycaemic control and competence of diabetes self-management in patients with diabetes mellitus. Patients were eligible if they had type 1 or 2 diabetes mellitus, were over 18 years of age and had participated in a 4 day group education programme offered at a diabetes clinic at a university hospital in Denmark. Exclusion criteria included pregnancy, severe debilitating disease and cognitive deficit. Out of 469 patients who attended the group education programme, 349 patients were randomised to either a usual care control group or an intervention group, which received up to five individual counselling sessions in 1 year based on MI, in addition to usual care. A randomised parallel design was used and open-label allocation was done by random permuted blocks, with allocation concealment by sequentially numbered, sealed, opaque envelopes. The primary outcome was glycated haemoglobin (HbA(1c)). Analysis regarding measurements of glycated haemoglobin (HbA(1c)) and competence of self-management (using the Problem Areas in Diabetes Scale [PAID] and Perceived Competence for Diabetes Scale [PCDS]) was based on 298 participants followed for a 24 month period. Data were collected at the Department of Endocrinology at Odense University Hospital. Our hypotheses were that MI could: (1) reduce HbA(1c) levels; (2) increase self-efficacy; and (3) increase diabetes self-care, compared with usual care. Out of the 176 included in the control group and 173 in the intervention group, 153 and 145 were analysed in the groups, respectively. When using the baseline value as covariate there were no significant differences in change score between the two study groups with regard to mean level of HbA(1c) (0.131, p = 0.221), PAID scores (-1.793, p = 0.191) or PCDS scores (0.017, p = 0.903) at the 24 month follow-up, using a mixed effects regression model. The patients in the intervention group showed significantly higher levels of perceived competence in dealing with diabetes compared with the control group (mean change score = -0.387, p = 0.002) following 1 year of intervention. We were unable to demonstrate any benefit, over or above usual care, of MI in patients with diabetes who have just completed a diabetes education programme, and who have well-regulated diabetes. Clinical Trials NCT00555854.

The impact of price and nutrition labelling on sugary drink purchases: Results from an experimental marketplace study.

PubMed

Acton, Rachel B; Hammond, David

2018-02-01

To examine the effect of front-of-package (FOP) nutrition labelling and sugary drink taxation on consumer beverage purchases. A total of 675 respondents aged 16 years and older participated in an experimental marketplace study using a 4 × 5 within-between group design. Participants were randomised to one of four labelling conditions (no label; star rating; high sugar symbol; health warning) and completed five within-subject purchase tasks. Beverage prices in each task corresponded to 'tax' conditions: 0%, 10%, 20%, 30% and a variable tax proportional to free sugar level. In each task, participants selected from 20 commercially available beverages; upon conclusion, one of five selections was randomly chosen for purchase. As price increased, participants were significantly less likely to select a sugary drink, and selected drinks with fewer calories and less free sugar (p < 0.001 for all). The overall effect of labelling was not statistically significant, although there was a trend for the 'high sugar' label to reduce the likelihood of selecting a sugary drink (p = 0.11) and encouraging participants to select drinks with less free sugar (p = 0.11). Increasing price was associated with reduced sugary drink purchases. Enhanced FOP labelling results highlight the need for further research to investigate their potential impact. The study adds empirical support for taxation to reduce sugary drink consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation.

PubMed

Bensdorp, A J; Tjon-Kon-Fat, R I; Bossuyt, P M M; Koks, C A M; Oosterhuis, G J E; Hoek, A; Hompes, P G A; Broekmans, F J M; Verhoeve, H R; de Bruin, J P; van Golde, R; Repping, S; Cohlen, B J; Lambers, M D A; van Bommel, P F; Slappendel, E; Perquin, D; Smeenk, J M; Pelinck, M J; Gianotten, J; Hoozemans, D A; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W J; van Wely, M

2015-01-09

To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. 17 centres in the Netherlands. Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates.Trial registration Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939. © Bensdorp et al 2015.

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.

PubMed

Möller, Hans-Jürgen; Demyttenaere, Koen; Olausson, Bengt; Szamosi, Johan; Wilson, Ellis; Hosford, David; Dunbar, Geoffrey; Tummala, Raj; Eriksson, Hans

2015-10-01

To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

PubMed

Kluckow, Martin; Jeffery, Michele; Gill, Andy; Evans, Nick

2014-03-01

Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. Multicentre, double-blind, placebo-controlled randomised trial. Three neonatal intensive care units in Australia. Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. Death or abnormal cranial ultrasound. The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

Evidence That Counts--What Happens When Teachers Apply Scientific Methods to Their Practice: Twelve Teacher-Led Randomised Controlled Trials and Other Styles of Experimental Research

ERIC Educational Resources Information Center

Churches, Richard; McAleavy, Tony

2015-01-01

This publication contains 12 (A3 open-out) poster-style reports of teacher experimental research. The style of presentation parallels the type of preliminary reporting common at academic conferences and postgraduate events. At the same time, it aims to act as a form of short primer to introduce teachers to the basic options that there are when…

Parallel closure theory for toroidally confined plasmas

NASA Astrophysics Data System (ADS)

Ji, Jeong-Young; Held, Eric D.

2017-10-01

We solve a system of general moment equations to obtain parallel closures for electrons and ions in an axisymmetric toroidal magnetic field. Magnetic field gradient terms are kept and treated using the Fourier series method. Assuming lowest order density (pressure) and temperature to be flux labels, the parallel heat flow, friction, and viscosity are expressed in terms of radial gradients of the lowest-order temperature and pressure, parallel gradients of temperature and parallel flow, and the relative electron-ion parallel flow velocity. Convergence of closure quantities is demonstrated as the number of moments and Fourier modes are increased. Properties of the moment equations in the collisionless limit are also discussed. Combining closures with fluid equations parallel mass flow and electric current are also obtained. Work in collaboration with the PSI Center and supported by the U.S. DOE under Grant Nos. DE-SC0014033, DE-SC0016256, and DE-FG02-04ER54746.

Minimum number of clusters and comparison of analysis methods for cross sectional stepped wedge cluster randomised trials with binary outcomes: A simulation study.

PubMed

Barker, Daniel; D'Este, Catherine; Campbell, Michael J; McElduff, Patrick

2017-03-09

Stepped wedge cluster randomised trials frequently involve a relatively small number of clusters. The most common frameworks used to analyse data from these types of trials are generalised estimating equations and generalised linear mixed models. A topic of much research into these methods has been their application to cluster randomised trial data and, in particular, the number of clusters required to make reasonable inferences about the intervention effect. However, for stepped wedge trials, which have been claimed by many researchers to have a statistical power advantage over the parallel cluster randomised trial, the minimum number of clusters required has not been investigated. We conducted a simulation study where we considered the most commonly used methods suggested in the literature to analyse cross-sectional stepped wedge cluster randomised trial data. We compared the per cent bias, the type I error rate and power of these methods in a stepped wedge trial setting with a binary outcome, where there are few clusters available and when the appropriate adjustment for a time trend is made, which by design may be confounding the intervention effect. We found that the generalised linear mixed modelling approach is the most consistent when few clusters are available. We also found that none of the common analysis methods for stepped wedge trials were both unbiased and maintained a 5% type I error rate when there were only three clusters. Of the commonly used analysis approaches, we recommend the generalised linear mixed model for small stepped wedge trials with binary outcomes. We also suggest that in a stepped wedge design with three steps, at least two clusters be randomised at each step, to ensure that the intervention effect estimator maintains the nominal 5% significance level and is also reasonably unbiased.

Developing an Australian-first recovery model for parents in Victorian mental health and family services: a study protocol for a randomised controlled trial.

PubMed

Maybery, Darryl; Goodyear, Melinda; Reupert, Andrea; Sheen, Jade; Cann, Warren; Dalziel, Kim; Tchernagovski, Phillip; O'Hanlon, Brendan; von Doussa, Henry

2017-05-26

A considerable number of people with a mental illness are parents caring for dependent children. For those with a mental illness, parenting can provide a sense of competence, belonging, identity and hope and hence is well aligned to the concept of personal recovery. However, little research has focused on the recovery journey of those who are parents and have a mental illness. This randomised controlled trial aims to (i) evaluate the effectiveness of an intervention model of recovery for parents (Let's Talk about Children) in three different mental health service sectors and (ii) examine the economic value of a larger roll out (longer term) of the parent recovery model. A two arm parallel randomised controlled trial will be used with participants, who are being treated for their mental illness in adult mental health, non-government community mental health or family welfare services. The study will involve 192 parents, who are considered by their treating practitioner to be sufficiently well to provide informed consent and participate in an intervention (Let's Talk about Children) or control group (treatment as usual). Participant randomisation will occur at the level of the treating practitioner and will be based on whether the randomised practitioner is trained in the intervention. Outcomes are compared at pre, post intervention and six-month follow-up. Recovery, parenting and family functioning, and quality of life questionnaires will be used to measure parent wellbeing and the economic benefits of the intervention. This is the first randomised controlled trial to investigate the efficacy of a parenting intervention on recovery outcomes and the first to provide an economic evaluation of an intervention for parents with a mental illness. An implementation model is required to embed the intervention in different sectors. The trial was retrospectively registered: ACTRN12616000460404 on the 8/4/2016.

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.

PubMed

Vibholm, Helle Annette; Pedersen, Jesper; Faltinsen, Erlend; Marcussen, Michael H; Gluud, Christian; Storebø, Ole Jakob

2018-06-08

This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up. In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.

The clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial

PubMed Central

Crawford, Mike J; Sanatinia, Rahil; Barrett, Barbara; Byford, Sarah; Dean, Madeleine; Green, John; Jones, Rachael; Leurent, Baptiste; Sweeting, Michael J; Touquet, Robin; Greene, Linda; Tyrer, Peter; Ward, Helen; Lingford-Hughes, Anne

2015-01-01

Objectives To examine the clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people who attend sexual health clinics. Methods Two-arm, parallel group, assessor blind, pragmatic, randomised controlled trial. 802 people aged 19 years or over who attended one of three sexual health clinics and were drinking excessively were randomised to either brief advice or control treatment. Brief advice consisted of feedback on alcohol and health, written information and an offer of an appointment with an Alcohol Health Worker. Control participants received a leaflet on health and lifestyle. The primary outcome was mean weekly alcohol consumption during the previous 90 days measured 6 months after randomisation. The main secondary outcome was unprotected sex during this period. Results Among the 402 randomised to brief advice, 397 (99%) received it. The adjusted mean difference in alcohol consumption at 6 months was −2.33 units per week (95% CI −4.69 to 0.03, p=0.053) among those in the active compared to the control arm of the trial. Unprotected sex was reported by 154 (53%) of those who received brief advice, and 178 (59%) controls (adjusted OR=0.89, 95% CI 0.63 to 1.25, p=0.496). There were no significant differences in costs between study groups at 6 months. Conclusions Introduction of universal screening and brief advice for excessive alcohol use among people attending sexual health clinics does not result in clinically important reductions in alcohol consumption or provide a cost-effective use of resources. Trial registration number Current Controlled Trials ISRCTN 99963322. PMID:24936090

ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

PubMed

Coyle, Christopher; Cafferty, Fay H; Rowley, Samuel; MacKenzie, Mairead; Berkman, Lindy; Gupta, Sudeep; Pramesh, C S; Gilbert, Duncan; Kynaston, Howard; Cameron, David; Wilson, Richard H; Ring, Alistair; Langley, Ruth E

2016-11-01

There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy. Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100mg aspirin, 300mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥75years old are only randomised to 100mg aspirin or placebo due to increased toxicity risk. The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures. The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Can Healthcare Assistant Training (CHAT) improve the relational care of older people? Study protocol for a pilot cluster randomised controlled trial.

PubMed

Arthur, Antony; Maben, Jill; Wharrad, Heather; Aldus, Clare; Sarre, Sophie; Schneider, Justine; Nicholson, Caroline; Barton, Garry; Cox, Karen; Clark, Allan

2015-12-09

People aged 75 years and over account for 1 in 4 of all hospital admissions. There has been increasing recognition of problems in the care of older people, particularly in hospitals. Evidence suggests that older people judge the care they receive in terms of kindness, empathy, compassion, respectful communication and being seen as a person not just a patient. These are aspects of care to which we refer when we use the term 'relational care'. Healthcare assistants deliver an increasing proportion of direct care to older people, yet their training needs are often overlooked. This study will determine the acceptability and feasibility of a cluster randomised controlled trial of 'Older People's Shoes' a 2-day training intervention for healthcare assistants caring for older people in hospital. Within this pilot, 2-arm, parallel, cluster randomised controlled trial, healthcare assistants within acute hospital wards are randomised to either the 2-day training intervention or training as usual. Registered nurses deliver 'Older People's Shoes' over 2 days, approximately 1 week apart. It contains three components: experiential learning about ageing, exploration of older people's stories, and customer care. Outcomes will be measured at the level of patient (experience of emotional care and quality of life during their hospital stay), healthcare assistant (empathy and attitudes towards older people), and ward (quality of staff/patient interaction). Semi-structured interviews of a purposive sample of healthcare assistants receiving the intervention, and all trainers delivering the intervention, will be undertaken to gain insights into the experiences of both the intervention and the trial, and its perceived impact on practice. Few training interventions for care staff have been rigorously tested using randomised designs. This study will establish the viability of a definitive cluster randomised controlled trial of a new training intervention to improve the relational care proided by healthcare assistants working with older people in hospital. The study was registered as an International Standard Randomised Controlled Trial ( ISRCTN10385799 ) on 29 December 2014.

Supplemental parenteral nutrition in critically ill patients: a study protocol for a phase II randomised controlled trial.

PubMed

Ridley, Emma J; Davies, Andrew R; Parke, Rachael; Bailey, Michael; McArthur, Colin; Gillanders, Lyn; Cooper, David J; McGuinness, Shay

2015-12-24

Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill. This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first). This trial aims to determine if provision of a supplemental parenteral nutrition strategy to critically ill adults will increase energy intake compared to usual care in Australia and New Zealand. Trial outcomes will guide development of a subsequent larger randomised controlled trial. NCT01847534 (First registered 5 February 2013, last updated 14 October 2015).

Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids

PubMed Central

2013-01-01

Background Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids. Methods/Design Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care. Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months. Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg). Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l). Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke. Primary outcome: Addenbrooke’s Cognitive Examination-Revised. Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures. Randomisation: using stratification, minimization and simple randomization. Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management. Discussion The PODCAST trial is ongoing with 78 patients recruited to date from 22 sites. Outcomes of cognitive impairment and dementia are accruing. Trial registration ISRCTN85562386 PMID:24266960

Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study.

PubMed

Kalff, Anna; Kennedy, Nola; Smiley, Angela; Prince, H Miles; Roberts, Andrew W; Bradstock, Kenneth; De Abreu Lourenço, Richard; Frampton, Chris; Spencer, Andrew

2014-12-01

We previously showed that consolidation therapy with thalidomide and prednisolone improved progression-free and overall survival in patients with multiple myeloma who had undergone autologous stem-cell transplantation. We aimed to assess whether these survival advantages were durable at 5 years. The ALLG MM6 trial was a multicentre, open-label, randomised phase 3 trial done between Jan 13, 2002, and March 15, 2005, at 29 sites in Australia and New Zealand. Patients with newly diagnosed multiple myeloma were randomly assigned (1:1), via computer-generated randomisation charts, to receive indefinite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratified by treating centre and pre-transplantation concentrations of β2 microglobulin. Patients and treating physicians were not masked to treatment allocation. Primary endpoints were progression-free survival and overall survival. Analysis was by intention to treat. Secondary endpoints were overall response to salvage therapy, incidence of second primary malignancy incidence, and cost-effectiveness. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12607000382471. We randomly assigned 269 patients to the thalidomide (n=114) or control group (n=129). After a median follow-up of 5·4 years (IQR 3·1-7·2), estimated 5-year progression-free survival was 27% (95% CI 23-32) in the thalidomide group and 15% (11-18) in the control group (hazard ratio [HR] 0·16, 95% CI 0·044-0·58; p=0·0054) and 5-year overall survival was 66% (95% CI 61-70) and 47% (42-51), respectively (HR 0·12, 95% CI 0·028-0·56; p=0·0072). There was no difference in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-effectiveness ratio was AUS$26 996 per mean life-year gained. Consolidation therapy with thalidomide and prednisolone after autologous stem-cell transplantaion is an acceptable therapeutic approach when alternative drugs are not available. Pharmion Corporation, Novartis Pharmaceuticals, Amgen Australia, The Merrin Foundation, and Alfred Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomised controlled trial

PubMed Central

Navani, Neal; Nankivell, Matthew; Lawrence, David R; Lock, Sara; Makker, Himender; Baldwin, David R; Stephens, Richard J; Parmar, Mahesh K; Spiro, Stephen G; Morris, Stephen; Janes, Sam M

2015-01-01

Summary Background The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis. We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer. Methods In this open-label, multicentre, pragmatic, randomised controlled trial, we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer, from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or conventional diagnosis and staging (CDS), for further investigation and staging. If a target node could not be accessed by EBUS-TBNA, then endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was allowed as an alternative procedure. Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre. We used a telephone randomisation method with permuted blocks of four generated by a computer. Because of the nature of the intervention, masking of participants and consenting investigators was not possible. The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose. This trial is registered with ClinicalTrials.gov, number NCT00652769. Findings Between June 10, 2008, and July 4, 2011, we randomly allocated 133 patients to treatment: 66 to EBUS-TBNA and 67 to CDS (one later withdrew consent). Two patients from the EBUS-TBNA group underwent EUS-FNA. The median time to treatment decision was shorter with EBUS-TBNA (14 days; 95% CI 14–15) than with CDS (29 days; 23–35) resulting in a hazard ratio of 1·98, (1·39–2·82, p<0·0001). One patient in each group had a pneumothorax from a CT-guided biopsy sample; the patient from the CDS group needed intercostal drainage and was admitted to hospital. Interpretation Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer, because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques. Funding UK Medical Research Council. PMID:25660225

A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK.

PubMed

Marlow, Robin; Kuriyakose, Sherine; Mesaros, Narcisa; Han, Htay Htay; Tomlinson, Richard; Faust, Saul N; Snape, Matthew D; Pollard, Andrew J; Finn, Adam

2018-04-19

To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV B ) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV). This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV B or dTap-IPV R ) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated. 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV B group and 130 in the dTap-IPV R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV B group. Non-inferiority of dTap-IPV B to dTap-IPV R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old. NCT01245049 (ClinicalTrials.gov). Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

PubMed

McDermott, Christopher J; Bradburn, Mike J; Maguire, Chin; Cooper, Cindy L; Baird, Wendy O; Baxter, Susan K; Cohen, Judith; Cantrill, Hannah; Dixon, Simon; Ackroyd, Roger; Baudouin, Simon; Bentley, Andrew; Berrisford, Richard; Bianchi, Stephen; Bourke, Stephen C; Darlison, Roy; Ealing, John; Elliott, Mark; Fitzgerald, Patrick; Galloway, Simon; Hamdalla, Hisham; Hanemann, C Oliver; Hughes, Philip; Imam, Ibrahim; Karat, Dayalan; Leek, Roger; Maynard, Nick; Orrell, Richard W; Sarela, Abeezar; Stradling, John; Talbot, Kevin; Taylor, Lyn; Turner, Martin; Simonds, Anita K; Williams, Tim; Wedzicha, Wisia; Young, Carolyn; Shaw, Pamela J

2016-06-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy. In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01). Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further. Current Controlled Trials ISRCTN53817913. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland.

Implementing Connected Component Labeling as a User Defined Operator for SciDB

NASA Technical Reports Server (NTRS)

Oloso, Amidu; Kuo, Kwo-Sen; Clune, Thomas; Brown, Paul; Poliakov, Alex; Yu, Hongfeng

2016-01-01

We have implemented a flexible User Defined Operator (UDO) for labeling connected components of a binary mask expressed as an array in SciDB, a parallel distributed database management system based on the array data model. This UDO is able to process very large multidimensional arrays by exploiting SciDB's memory management mechanism that efficiently manipulates arrays whose memory requirements far exceed available physical memory. The UDO takes as primary inputs a binary mask array and a binary stencil array that specifies the connectivity of a given cell to its neighbors. The UDO returns an array of the same shape as the input mask array with each foreground cell containing the label of the component it belongs to. By default, dimensions are treated as non-periodic, but the UDO also accepts optional input parameters to specify periodicity in any of the array dimensions. The UDO requires four stages to completely label connected components. In the first stage, labels are computed for each subarray or chunk of the mask array in parallel across SciDB instances using the weighted quick union (WQU) with half-path compression algorithm. In the second stage, labels around chunk boundaries from the first stage are stored in a temporary SciDB array that is then replicated across all SciDB instances. Equivalences are resolved by again applying the WQU algorithm to these boundary labels. In the third stage, relabeling is done for each chunk using the resolved equivalences. In the fourth stage, the resolved labels, which so far are "flattened" coordinates of the original binary mask array, are renamed with sequential integers for legibility. The UDO is demonstrated on a 3-D mask of O(1011) elements, with O(108) foreground cells and O(106) connected components. The operator completes in 19 minutes using 84 SciDB instances.

Modeling an in-register, parallel "iowa" aβ fibril structure using solid-state NMR data from labeled samples with rosetta.

PubMed

Sgourakis, Nikolaos G; Yau, Wai-Ming; Qiang, Wei

2015-01-06

Determining the structures of amyloid fibrils is an important first step toward understanding the molecular basis of neurodegenerative diseases. For β-amyloid (Aβ) fibrils, conventional solid-state NMR structure determination using uniform labeling is limited by extensive peak overlap. We describe the characterization of a distinct structural polymorph of Aβ using solid-state NMR, transmission electron microscopy (TEM), and Rosetta model building. First, the overall fibril arrangement is established using mass-per-length measurements from TEM. Then, the fibril backbone arrangement, stacking registry, and "steric zipper" core interactions are determined using a number of solid-state NMR techniques on sparsely (13)C-labeled samples. Finally, we perform Rosetta structure calculations with an explicitly symmetric representation of the system. We demonstrate the power of the hybrid Rosetta/NMR approach by modeling the in-register, parallel "Iowa" mutant (D23N) at high resolution (1.2Å backbone rmsd). The final models are validated using an independent set of NMR experiments that confirm key features. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis.

PubMed

Garcia-del-Muro, X; Vadell, C; Pérez Manga, G; Bover, I; Rifá, J; Beltrán, M; Barros, M M; Germá, J R; Fabregat, X; Moreno, V; Salvador, A; Viladiu, P

1998-01-01

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Pancreatitis, very early compared with normal start of enteral feeding (PYTHON trial): design and rationale of a randomised controlled multicenter trial

PubMed Central

2011-01-01

Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985 PMID:21392395

Bimatoprost 0.03%/timolol 0.5% preservative-free ophthalmic solution versus bimatoprost 0.03%/timolol 0.5% ophthalmic solution (Ganfort) for glaucoma or ocular hypertension: a 12-week randomised controlled trial

PubMed Central

Goldberg, Ivan; Gil Pina, Rafael; Lanzagorta-Aresti, Aitor; Schiffman, Rhett M; Liu, Charlie; Bejanian, Marina

2014-01-01

Aim To compare the efficacy and safety of single-dose bimatoprost 0.03%/timolol 0.5% preservative-free (PF) ophthalmic solution with bimatoprost 0.03%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. Methods In this multicentre, randomised, parallel-group study, patients were randomised to bimatoprost/timolol PF or bimatoprost/timolol once daily in the morning for 12 weeks. Primary efficacy endpoints, reflecting differing regional regulatory requirements, included change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12, and the average eye IOP at weeks 2, 6 and 12 in the intent-to-treat population. Results 561 patients were randomised (278 to bimatoprost/timolol PF; 283 to bimatoprost/timolol); 96.3% completed the study. Both treatment groups showed statistically and clinically significant mean decreases from baseline in worse eye IOP and in average eye IOP at all follow-up time points (p<0.001). Bimatoprost/timolol PF met all pre-established criteria for non-inferiority and equivalence to bimatoprost/timolol. Ocular adverse events were similar between treatment groups, with conjunctival hyperaemia being the most frequent. Most were mild or moderate in severity. Conclusions Bimatoprost/timolol PF demonstrated non-inferiority and equivalence in IOP lowering compared with bimatoprost/timolol, with no significant differences in safety and tolerability. Trial registration number NCT01177098. PMID:24667994

Randomised social-skills training and parental training plus standard treatment versus standard treatment of children with attention deficit hyperactivity disorder - The SOSTRA trial protocol

PubMed Central

2011-01-01

Background Children with attention deficit hyperactivity disorder (ADHD) are hyperactive and impulsive, cannot maintain attention, and have difficulties with social interactions. Medical treatment may alleviate symptoms of ADHD, but seldom solves difficulties with social interactions. Social-skills training may benefit ADHD children in their social interactions. We want to examine the effects of social-skills training on difficulties related to the children's ADHD symptoms and social interactions. Methods/Design The design is randomised two-armed, parallel group, assessor-blinded trial. Children aged 8-12 years with a diagnosis of ADHD are randomised to social-skills training and parental training plus standard treatment versus standard treatment alone. A sample size calculation estimated that at least 52 children must be included to show a 4-point difference in the primary outcome on the Conners 3rd Edition subscale for 'hyperactivity-impulsivity' between the intervention group and the control group. The outcomes will be assessed 3 and 6 months after randomisation. The primary outcome measure is ADHD symptoms. The secondary outcome is social skills. Tertiary outcomes include the relationship between social skills and symptoms of ADHD, the ability to form attachment, and parents' ADHD symptoms. Discussion We hope that the results from this trial will show that the social-skills training together with medication may have a greater general effect on ADHD symptoms and social and emotional competencies than medication alone. Trial registration ClinicalTrials (NCT): NCT00937469 PMID:21255399

Sample size calculations for cluster randomised crossover trials in Australian and New Zealand intensive care research.

PubMed

Arnup, Sarah J; McKenzie, Joanne E; Pilcher, David; Bellomo, Rinaldo; Forbes, Andrew B

2018-06-01

The cluster randomised crossover (CRXO) design provides an opportunity to conduct randomised controlled trials to evaluate low risk interventions in the intensive care setting. Our aim is to provide a tutorial on how to perform a sample size calculation for a CRXO trial, focusing on the meaning of the elements required for the calculations, with application to intensive care trials. We use all-cause in-hospital mortality from the Australian and New Zealand Intensive Care Society Adult Patient Database clinical registry to illustrate the sample size calculations. We show sample size calculations for a two-intervention, two 12-month period, cross-sectional CRXO trial. We provide the formulae, and examples of their use, to determine the number of intensive care units required to detect a risk ratio (RR) with a designated level of power between two interventions for trials in which the elements required for sample size calculations remain constant across all ICUs (unstratified design); and in which there are distinct groups (strata) of ICUs that differ importantly in the elements required for sample size calculations (stratified design). The CRXO design markedly reduces the sample size requirement compared with the parallel-group, cluster randomised design for the example cases. The stratified design further reduces the sample size requirement compared with the unstratified design. The CRXO design enables the evaluation of routinely used interventions that can bring about small, but important, improvements in patient care in the intensive care setting.

Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study.

PubMed

Molina, Jean-Michel; Charreau, Isabelle; Spire, Bruno; Cotte, Laurent; Chas, Julie; Capitant, Catherine; Tremblay, Cecile; Rojas-Castro, Daniela; Cua, Eric; Pasquet, Armelle; Bernaud, Camille; Pintado, Claire; Delaugerre, Constance; Sagaon-Teyssier, Luis; Mestre, Soizic Le; Chidiac, Christian; Pialoux, Gilles; Ponscarme, Diane; Fonsart, Julien; Thompson, David; Wainberg, Mark A; Doré, Veronique; Meyer, Laurence

2017-09-01

Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an open-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials.gov, number NCT01473472. Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18·4 months (IQR 17·7-19·1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0·19 per 100 person-years (95% CI 0·01-1·08), compared with 6·60 per 100 person-years (3·60-11·05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with on-demand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend=0·0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59·0 vs 49·1 per 100 person-years, respectively; p=0·11). On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing. ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé-Sidaction, Gilead Sciences, and the Bill & Melinda Gates Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial

PubMed Central

Toffolo, Antonella; Zucchetta, Pietro; Dall'Amico, Roberto; Gobber, Daniela; Calderan, Alessandro; Maschio, Francesca; Pavanello, Luigi; Molinari, Pier Paolo; Scorrano, Dante; Zanchetta, Sergio; Cassar, Walburga; Brisotto, Paolo; Corsini, Andrea; Sartori, Stefano; Dalt, Liviana Da; Murer, Luisa; Zacchello, Graziella

2007-01-01

Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. Design Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. Setting 28 paediatric units in north east Italy. Participants 502 children aged 1 month to <7 years with clinical pyelonephritis. Intervention Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37°C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. Results Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk −4%, 95% confidence interval −11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (−0.9 to 6.0); white cell count 9.8×109/l (SD 3.5) v 9.5×109/l (SD 3.1), mean difference 0.3 (−0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference −0.05% (−1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. Trial registration Clinical Trials NCT00161330. PMID:17611232

Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial.

PubMed

Bourdel-Marchasson, Isabelle; Blanc-Bisson, Christelle; Doussau, Adélaïde; Germain, Christine; Blanc, Jean-Frédéric; Dauba, Jérôme; Lahmar, Cyril; Terrebonne, Eric; Lecaille, Cédric; Ceccaldi, Joël; Cany, Laurent; Lavau-Denes, Sandrine; Houede, Nadine; Chomy, François; Durrieu, Jessica; Soubeyran, Pierre; Senesse, Pierre; Chene, Geneviève; Fonck, Mariane

2014-01-01

We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality. We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1∶1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes. Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4·9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p<0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups. Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect. ClinicalTrials.gov NCT00459589.

Testing the activitystat hypothesis: a randomised controlled trial protocol.

PubMed

Gomersall, Sjaan; Maher, Carol; Norton, Kevin; Dollman, Jim; Tomkinson, Grant; Esterman, Adrian; English, Coralie; Lewis, Nicole; Olds, Tim

2012-10-08

The activitystat hypothesis proposes that when physical activity or energy expenditure is increased or decreased in one domain, there will be a compensatory change in another domain to maintain an overall, stable level of physical activity or energy expenditure. To date, there has been no experimental study primarily designed to test the activitystat hypothesis in adults. The aim of this trial is to determine the effect of two different imposed exercise loads on total daily energy expenditure and physical activity levels. This study will be a randomised, multi-arm, parallel controlled trial. Insufficiently active adults (as determined by the Active Australia survey) aged 18-60 years old will be recruited for this study (n=146). Participants must also satisfy the Sports Medicine Australia Pre-Exercise Screening System and must weigh less than 150 kg. Participants will be randomly assigned to one of three groups using a computer-generated allocation sequence. Participants in the Moderate exercise group will receive an additional 150 minutes of moderate to vigorous physical activity per week for six weeks, and those in the Extensive exercise group will receive an additional 300 minutes of moderate to vigorous physical activity per week for six weeks. Exercise targets will be accumulated through both group and individual exercise sessions monitored by heart rate telemetry. Control participants will not be given any instructions regarding lifestyle. The primary outcome measures are activity energy expenditure (doubly labeled water) and physical activity (accelerometry). Secondary measures will include resting metabolic rate via indirect calorimetry, use of time, maximal oxygen consumption and several anthropometric and physiological measures. Outcome measures will be conducted at baseline (zero weeks), mid- and end-intervention (three and six weeks) with three (12 weeks) and six month (24 week) follow-up. All assessors will be blinded to group allocation. This protocol has been specifically designed to test the activitystat hypothesis while taking into account the key conceptual and methodological considerations of testing a biologically regulated homeostatic feedback loop. Results of this study will be an important addition to the growing literature and debate concerning the possible existence of an activitystat. Australian New Zealand Clinical Trials Registry ACTRN12610000248066.

A randomised controlled trial of a complex intervention to reduce children’s exposure to secondhand smoke in the home

PubMed Central

Thorley, Rebecca; Jones, Laura; Opazo Breton, Magdalena; Cook, Juliette; McNeill, Ann; Britton, John; Coleman, Tim; Lewis, Sarah

2018-01-01

Objectives Exposing children to secondhand tobacco smoke (SHS) causes significant harm and occurs predominantly through smoking by caregivers in the family home. We report a trial of a complex intervention designed to reduce secondhand smoke exposure of children whose primary caregiver feels unable or unwilling to quit smoking. Design An open-label, parallel, randomised controlled trial. Setting Deprived communities in Nottingham City and County, England Participants Caregivers resident in Nottingham City and County in England who were at least 18 years old, the main caregiver of a child aged under 5 years living in their household, and reported that they were smoking tobacco inside their home. Interventions We compared a complex intervention combining personalised feedback on home air quality, behavioural support and nicotine replacement therapy for temporary abstinence with usual care. Main outcomes The primary outcome was change in air quality in the home, measured as average 16–24  hours levels of particulate matter of  < 2.5  µm diameter (PM2.5), between baseline and 12 weeks. Secondary outcomes included changes in maximum PM2.5, proportion of time PM2.5 exceeded WHO recommended levels of maximum exposure of 25  µg/mg3, child salivary cotinine, caregivers’ cigarette consumption, nicotine dependence, determination to stop smoking, quit attempts and quitting altogether during the intervention. Results Arithmetic mean PM2.5 decreased significantly more (by 35.2 %; 95%  CI 12.7% to 51.9 %) in intervention than in usual care households, as did the proportion of time PM2.5 exceeded 25  µg/mg3, child salivary cotinine concentrations, caregivers’ cigarette consumption in the home, nicotine dependence, determination to quit and likelihood of having made a quit attempt. Conclusions By reducing exposure to SHS in the homes of children who live with smokers unable or unwilling to quit, this intervention offers huge potential to reduce children’s’ tobacco-related harm. Trial registration number ISRCTN81701383. This trial was funded by the UK National Institute for Health Research (NIHR): RP-PG-0608-10020 PMID:28432210

Testing the activitystat hypothesis: a randomised controlled trial protocol

PubMed Central

2012-01-01

Background The activitystat hypothesis proposes that when physical activity or energy expenditure is increased or decreased in one domain, there will be a compensatory change in another domain to maintain an overall, stable level of physical activity or energy expenditure. To date, there has been no experimental study primarily designed to test the activitystat hypothesis in adults. The aim of this trial is to determine the effect of two different imposed exercise loads on total daily energy expenditure and physical activity levels. Methods This study will be a randomised, multi-arm, parallel controlled trial. Insufficiently active adults (as determined by the Active Australia survey) aged 18–60 years old will be recruited for this study (n=146). Participants must also satisfy the Sports Medicine Australia Pre-Exercise Screening System and must weigh less than 150 kg. Participants will be randomly assigned to one of three groups using a computer-generated allocation sequence. Participants in the Moderate exercise group will receive an additional 150 minutes of moderate to vigorous physical activity per week for six weeks, and those in the Extensive exercise group will receive an additional 300 minutes of moderate to vigorous physical activity per week for six weeks. Exercise targets will be accumulated through both group and individual exercise sessions monitored by heart rate telemetry. Control participants will not be given any instructions regarding lifestyle. The primary outcome measures are activity energy expenditure (doubly labeled water) and physical activity (accelerometry). Secondary measures will include resting metabolic rate via indirect calorimetry, use of time, maximal oxygen consumption and several anthropometric and physiological measures. Outcome measures will be conducted at baseline (zero weeks), mid- and end-intervention (three and six weeks) with three (12 weeks) and six month (24 week) follow-up. All assessors will be blinded to group allocation. Discussion This protocol has been specifically designed to test the activitystat hypothesis while taking into account the key conceptual and methodological considerations of testing a biologically regulated homeostatic feedback loop. Results of this study will be an important addition to the growing literature and debate concerning the possible existence of an activitystat. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12610000248066 PMID:23043381

Effect of Training on the Reliability of Satiety Evaluation and Use of Trained Panellists to Determine the Satiety Effect of Dietary Fibre: A Randomised Controlled Trial

PubMed Central

Solah, Vicky A.; Meng, Xingqiong; Wood, Simon; Gahler, Roland J.; Kerr, Deborah A.; James, Anthony P.; Pal, Sebely; Fenton, Haelee K.; Johnson, Stuart K.

2015-01-01

Background The assessment of satiety effects on foods is commonly performed by untrained volunteers marking their perceived hunger or fullness on line scales, marked with pre-set descriptors. The lack of reproducibility of satiety measurement using this approach however results in the tool being unable to distinguish between foods that have small, but possibly important, differences in their satiety effects. An alternate approach is used in sensory evaluation; panellists can be trained in the correct use of the assessment line-scale and brought to consensus on the meanings of descriptors used for food quality attributes to improve the panel reliability. The effect of training on the reliability of a satiety panel has not previously been reported. Method In a randomised controlled parallel intervention, the effect of training in the correct use of a satiety labelled magnitude scale (LMS) was assessed versus no-training. The test-retest precision and reliability of two hour postprandial satiety evaluation after consumption of a standard breakfast was compared. The trained panel then compared the satiety effect of two breakfast meals containing either a viscous or a non-viscous dietary fibre in a crossover trial. Results A subgroup of the 23 panellists (n = 5) improved their test re-test precision after training. Panel satiety area under the curve, “after the training” intervention was significantly different to “before training” (p < 0.001). Reliability of the panel determined by intraclass correlation (ICC) of test and retest showed improved strength of the correlation from 0.70 pre-intervention to 0.95 post intervention. The trained “satiety expert panel” determined that a standard breakfast with 5g of viscous fibre gave significantly higher satiety than with 5g non-viscous fibre (area under curve (AUC) of 478.2, 334.4 respectively) (p ≤ 0.002). Conclusion Training reduced between panellist variability. The improved strength of test-retest ICC as a result of the training intervention suggests that training satiety panellists can improve the discriminating power of satiety evaluation. PMID:25978321

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol.

PubMed

Figueras, Francesc; Gratacos, Eduard; Rial, Marta; Gull, Ilan; Krofta, Ladislav; Lubusky, Marek; Cruz-Martinez, Rogelio; Cruz-Lemini, Mónica; Martinez-Rodriguez, Miguel; Socias, Pamela; Aleuanlli, Cristina; Cordero, Mauro C Parra

2017-06-15

Fetal growth restriction (FGR) affects 5%-10% of all pregnancies, contributing to 30%-50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19 +0 -22 +6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36 +0 -37 +6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36 +0 -37 +6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. NCT02907242; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of training on the reliability of satiety evaluation and use of trained panellists to determine the satiety effect of dietary fibre: a randomised controlled trial.

PubMed

Solah, Vicky A; Meng, Xingqiong; Wood, Simon; Gahler, Roland J; Kerr, Deborah A; James, Anthony P; Pal, Sebely; Fenton, Haelee K; Johnson, Stuart K

2015-01-01

The assessment of satiety effects on foods is commonly performed by untrained volunteers marking their perceived hunger or fullness on line scales, marked with pre-set descriptors. The lack of reproducibility of satiety measurement using this approach however results in the tool being unable to distinguish between foods that have small, but possibly important, differences in their satiety effects. An alternate approach is used in sensory evaluation; panellists can be trained in the correct use of the assessment line-scale and brought to consensus on the meanings of descriptors used for food quality attributes to improve the panel reliability. The effect of training on the reliability of a satiety panel has not previously been reported. In a randomised controlled parallel intervention, the effect of training in the correct use of a satiety labelled magnitude scale (LMS) was assessed versus no-training. The test-retest precision and reliability of two hour postprandial satiety evaluation after consumption of a standard breakfast was compared. The trained panel then compared the satiety effect of two breakfast meals containing either a viscous or a non-viscous dietary fibre in a crossover trial. A subgroup of the 23 panellists (n = 5) improved their test re-test precision after training. Panel satiety area under the curve, "after the training" intervention was significantly different to "before training" (p < 0.001). Reliability of the panel determined by intraclass correlation (ICC) of test and retest showed improved strength of the correlation from 0.70 pre-intervention to 0.95 post intervention. The trained "satiety expert panel" determined that a standard breakfast with 5g of viscous fibre gave significantly higher satiety than with 5g non-viscous fibre (area under curve (AUC) of 478.2, 334.4 respectively) (p ≤ 0.002). Training reduced between panellist variability. The improved strength of test-retest ICC as a result of the training intervention suggests that training satiety panellists can improve the discriminating power of satiety evaluation.

Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial.

PubMed

Engert, Andreas; Haverkamp, Heinz; Kobe, Carsten; Markova, Jana; Renner, Christoph; Ho, Antony; Zijlstra, Josée; Král, Zdenek; Fuchs, Michael; Hallek, Michael; Kanz, Lothar; Döhner, Hartmut; Dörken, Bernd; Engel, Nicole; Topp, Max; Klutmann, Susanne; Amthauer, Holger; Bockisch, Andreas; Kluge, Regine; Kratochwil, Clemens; Schober, Otmar; Greil, Richard; Andreesen, Reinhard; Kneba, Michael; Pfreundschuh, Michael; Stein, Harald; Eich, Hans Theodor; Müller, Rolf-Peter; Dietlein, Markus; Borchmann, Peter; Diehl, Volker

2012-05-12

The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPP(escalated) (8×B(esc) group), six cycles of BEACOPP(escalated) (6×B(esc) group), or eight cycles of BEACOPP(14) (8×B(14) group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041. Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×B(esc) group, 711 in the 6×B(esc) group, and 710 in the 8×B(14) group. Freedom from treatment failure was sequentially non-inferior for the 6×B(esc) and 8×B(14) groups as compared with 8×B(esc). 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0-87·7) for the 8×B(esc) group, 89·3% (86·5-92·1) for 6×B(esc) group, and 85·4% (82·1-88·7) for the 8×B(14) group (97·5% CI for difference between 6×B(esc) and 8×B(esc) was 0·5-9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×B(esc) than with 8×B(esc) (97·5% CI 0·2-6·5). The 8×B(esc) group showed a higher mortality (7·5%) than the 6×B(esc) (4·6%) and 8×B(14) (5·2%) groups, mainly due to differences in treatment-related events (2·1%, 0·8%, and 0·8%, respectively) and secondary malignancies (1·8%, 0·7%, and 1·1%, respectively). The negative predictive value for PET at 12 months was 94·1% (95% CI 92·1-96·1); and 225 (11%) of 2126 patients received additional radiotherapy. Treatment with six cycles of BEACOPP(escalated) followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPP(escalated) should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting. Deutsche Krebshilfe and the Swiss Federal Government. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial.

PubMed

Nakajima, Atsushi; Seki, Mitsunori; Taniguchi, Shinya; Ohta, Akira; Gillberg, Per-Göran; Mattsson, Jan P; Camilleri, Michael

2018-05-24

A subset of patients with constipation has reduced colonic bile acid concentrations, which are associated with slow colonic transit. In a previous study, elobixibat, a locally acting ileal bile acid transporter inhibitor, accelerated colonic transit in Japanese patients with functional constipation. In this study, we aimed to determine the efficacy of elobixibat for short-term treatment of chronic constipation, and safety, patient satisfaction, and quality of life with long-term treatment. We did two phase 3 studies of patients aged 20-80 years in Japan with at least 6 months of chronic constipation, who satisfied Rome III criteria for functional constipation, including fewer than three spontaneous bowel movements per week. The first trial, including patients enrolled at 16 clinics, was a 2-week, randomised, double-blind, placebo-controlled study in which (after a 2-week run-in period) patients were randomly assigned (1:1) to either elobixibat 10 mg/day for 2 weeks or placebo. Randomisation was done with permuted block method (block size six) without stratification. Masking to treatment allocation was achieved with identical appearances of elobixibat and placebo, which were supplied in sealed, opaque containers. Group assignment was concealed from patients, investigators, and analysts. The second trial, including patients enrolled at 34 clinics or hospitals, was an open-label, 1-year study in which all patients received elobixibat; participants could titrate the dose to 5 mg/day or 15 mg/day, or maintain the 10 mg/day dose. In both studies, participants took the study drug as an oral tablet once per day before breakfast. The primary outcome of the 2-week randomised trial was the change from baseline (ie, last week of the 2-week run-in) in the frequency of spontaneous bowel movements during week 1 of treatment. The primary outcome of the 52-week open-label trial was safety (type, severity, and incidence of adverse drug reactions) at all times from treatment initiation. All efficacy analyses were based on the modified intention-to-treat (ITT) population without imputation for any missing data. Safety analyses included all patients who received at least one dose of study drug. These trials are registered with the Japan Pharmaceutical Information Center (numbers JapicCTI-153061 and JapicCTI-153062) and have been completed. Between Nov 4, 2015, and June 11, 2016, we assigned 133 patients to treatment in the 2-week randomised trial: 70 to elobixibat (69 included in the modified ITT and safety populations) and 63 to placebo. The frequency of spontaneous bowel movements per week during week 1 of treatment was greater with elobixibat (least-squares mean 6·4, 95% CI 5·3-7·6) than with placebo (1·7, 1·2-2·2), p<0·0001). Between Oct 31, 2015, and March 15, 2017, we allocated 341 patients to 52 weeks of elobixibat (340 included in the modified ITT and safety populations). 163 (48%) patients in the 52-week trial had an adverse drug reaction, the most common of which were mild gastrointestinal disorders (in 135 [40%] patients). Inguinal hernia was reported in one patient with elobixibat in the 52-week study as a moderate adverse drug reaction. The most common adverse drug reactions in both trials were mild abdominal pain (13 [19%] patients with elobixibat and one [2%] with placebo in the 2-week randomised trial, and 82 [24%] patients in the 52-week trial) and diarrhoea (nine [13%] patients with elobixibat and none with placebo in the 2-week randomised trial and 50 [15%] in the 52-week trial). Elobixibat resolved constipation in the short-term, and was well tolerated with both short-term and long-term treatment. The evidence supports the use of this novel approach to increase intracolonic concentrations of endogenous bile acid for the treatment of chronic constipation. EA Pharma and Mochida Pharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modeling Central Carbon Metabolic Processes in Soil Microbial Communities: Comparing Measured With Modeled

NASA Astrophysics Data System (ADS)

Dijkstra, P.; Fairbanks, D.; Miller, E.; Salpas, E.; Hagerty, S.

2013-12-01

Understanding the mechanisms regulating C cycling is hindered by our inability to directly observe and measure the biochemical processes of glycolysis, pentose phosphate pathway, and TCA cycle in intact and complex microbial communities. Position-specific 13C labeled metabolic tracer probing is proposed as a new way to study microbial community energy production, biosynthesis, C use efficiency (the proportion of substrate incorporated into microbial biomass), and enables the quantification of C fluxes through the central C metabolic network processes (Dijkstra et al 2011a,b). We determined the 13CO2 production from U-13C, 1-13C, 2-13C, 3-13C, 4-13C, 5-13C, and 6-13C labeled glucose and 1-13C and 2,3-13C pyruvate in parallel incubations in three soils along an elevation gradient. Qualitative and quantitative interpretation of the results indicate a high pentose phosphate pathway activity in soils. Agreement between modeled and measured CO2 production rates for the six C-atoms of 13C-labeled glucose indicate that the metabolic model used is appropriate for soil community processes, but that improvements can be made. These labeling and modeling techniques may improve our ability to analyze the biochemistry and (eco)physiology of intact microbial communities. Dijkstra, P., Blankinship, J.C., Selmants, P.C., Hart, S.C., Koch, G.W., Schwartz, E., Hungate, B.A., 2011a. Probing C flux patterns of soil microbial metabolic networks using parallel position-specific tracer labeling. Soil Biology & Biochemistry 43, 126-132. Dijkstra, P., Dalder, J.J., Selmants, P.C., Hart, S.C., Koch, G.W., Schwartz, E., Hungate, B.A., 2011b. Modeling soil metabolic processes using isotopologue pairs of position-specific 13C-labeled glucose and pyruvate. Soil Biology & Biochemistry 43, 1848-1857.

Ethical analysis of the justifiability of labelling with COPD for smoking cessation.

PubMed

Kotz, D; Vos, R; Huibers, M J H

2009-09-01

Spirometry for early detection of chronic obstructive pulmonary disease (COPD) and smoking cessation is criticised because of the potential negative effects of labelling with disease. To assess the effects of opinions of smokers with mild to moderate COPD on the effectiveness of spirometry for smoking cessation, the justification of early detection of airflow limitation in smokers and the impact of confrontation with COPD. Qualitative study with data from a randomised controlled trial. General population of Dutch and Belgian Limburg. Semistructured ethical exit interviews were conducted with 205 smokers who were motivated to quit smoking and had no prior diagnosis of COPD but were detected with airflows limitation by means of spirometry. They received either (1) counselling, including labelling with COPD, plus with nortriptyline for smoking cessation, (2) counselling excluding labelling with COPD, plus nortriptyline for smoking cessation or (3) care as usual for smoking cessation by the general practitioner, without labelling with COPD. Of the participants, 177 (86%) agreed or completely agreed that it is justified to measure lung function in heavy smokers. These participants argued that measuring lung function raises consciousness of the negative effects of smoking, helps to prevent disease or increases motivation to stop smoking. Most of the 18 participants who disagreed argued that routinely measuring lung function in smokers would interfere with freedom of choice. Labelling with disease is probably a less important issue in the discussion about the pros and cons of early detection of COPD.

Clinical study to monitor dentinal hypersensitivity with episodic use of a desensitising dentifrice

PubMed Central

Mason, Stephen; Kingston, Rose; Shneyer, Lucy; Harding, Máiréad

2017-01-01

Objectives/Aims: To evaluate continuous and episodic twice-daily usage regimens of a desensitising dentifrice containing 5% calcium sodium phosphosilicate (CSPS). Materials and Methods: In this exploratory, single-centre, randomised, examiner-blind study, subjects with dentinal hypersensitivity were randomised to continuous (24 weeks) use of a 5% CSPS-containing dentifrice or episodic use of the dentifrice comprising two 8-week treatment periods separated by 8 weeks′ use of a standard fluoride dentifrice. Sensitivity was assessed by tactile threshold (Yeaple probe) and evaporative (air) sensitivity (Schiff sensitivity score). Other measures included labelled magnitude scales to assess subjects′ responses to the evaporative stimulus, the Dentine Hypersensitivity Experience Questionnaire and a tooth sensitivity question. Results: Seventy-six subjects were randomised to continuous (n=38) or episodic (n=38) use. Small but statistically significant improvements from baseline in Schiff sensitivity scores were observed at weeks 8, 16 and 24 with both regimens (all P<0.05). Increases from baseline in tactile threshold were not statistically significant. No significant between-regimen difference was observed for any endpoint. No treatment-related adverse events were reported. Discussion: Dentifrice containing 5% CSPS improved dentinal hypersensitivity with both episodic and continuous twice-daily usage regimens over 24 weeks and was well tolerated. Conclusion: No performance differences were observed between the two usage regimens. PMID:29789771

Parallel labeling experiments for pathway elucidation and (13)C metabolic flux analysis.

PubMed

Antoniewicz, Maciek R

2015-12-01

Metabolic pathway models provide the foundation for quantitative studies of cellular physiology through the measurement of intracellular metabolic fluxes. For model organisms metabolic models are well established, with many manually curated genome-scale model reconstructions, gene knockout studies and stable-isotope tracing studies. However, for non-model organisms a similar level of knowledge is often lacking. Compartmentation of cellular metabolism in eukaryotic systems also presents significant challenges for quantitative (13)C-metabolic flux analysis ((13)C-MFA). Recently, innovative (13)C-MFA approaches have been developed based on parallel labeling experiments, the use of multiple isotopic tracers and integrated data analysis, that allow more rigorous validation of pathway models and improved quantification of metabolic fluxes. Applications of these approaches open new research directions in metabolic engineering, biotechnology and medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fluorinated colloidal gold immunolabels for imaging select proteins in parallel with lipids using high-resolution secondary ion mass spectrometry

PubMed Central

Wilson, Robert L.; Frisz, Jessica F.; Hanafin, William P.; Carpenter, Kevin J.; Hutcheon, Ian D.; Weber, Peter K.; Kraft, Mary L.

2014-01-01

The local abundance of specific lipid species near a membrane protein is hypothesized to influence the protein’s activity. The ability to simultaneously image the distributions of specific protein and lipid species in the cell membrane would facilitate testing these hypotheses. Recent advances in imaging the distribution of cell membrane lipids with mass spectrometry have created the desire for membrane protein probes that can be simultaneously imaged with isotope labeled lipids. Such probes would enable conclusive tests of whether specific proteins co-localize with particular lipid species. Here, we describe the development of fluorine-functionalized colloidal gold immunolabels that facilitate the detection and imaging of specific proteins in parallel with lipids in the plasma membrane using high-resolution SIMS performed with a NanoSIMS. First, we developed a method to functionalize colloidal gold nanoparticles with a partially fluorinated mixed monolayer that permitted NanoSIMS detection and rendered the functionalized nanoparticles dispersible in aqueous buffer. Then, to allow for selective protein labeling, we attached the fluorinated colloidal gold nanoparticles to the nonbinding portion of antibodies. By combining these functionalized immunolabels with metabolic incorporation of stable isotopes, we demonstrate that influenza hemagglutinin and cellular lipids can be imaged in parallel using NanoSIMS. These labels enable a general approach to simultaneously imaging specific proteins and lipids with high sensitivity and lateral resolution, which may be used to evaluate predictions of protein co-localization with specific lipid species. PMID:22284327

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563)

PubMed Central

2014-01-01

Background Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients’ short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Methods/design Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. Discussion This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates. Trial registration ISRCTN: ISRCTN93634563. PMID:25064573

A multicentre, pragmatic, parallel group, randomised controlled trial to compare the clinical and cost-effectiveness of three physiotherapy-led exercise interventions for knee osteoarthritis in older adults: the BEEP trial protocol (ISRCTN: 93634563).

PubMed

Foster, Nadine E; Healey, Emma L; Holden, Melanie A; Nicholls, Elaine; Whitehurst, David Gt; Jowett, Susan; Jinks, Clare; Roddy, Edward; Hay, Elaine M

2014-07-27

Exercise is consistently recommended for older adults with knee pain related to osteoarthritis. However, the effects from exercise are typically small and short-term, likely linked to insufficient individualisation of the exercise programme and limited attention to supporting exercise adherence over time. The BEEP randomised trial aims to improve patients' short and long-term outcomes from exercise. It will test the overall effectiveness and cost-effectiveness of two physiotherapy-led exercise interventions (Individually Tailored Exercise and Targeted Exercise Adherence) to improve the individual tailoring of, and adherence to exercise, compared with usual physiotherapy care. Based on the learning from a pilot study (ISRCTN 23294263), the BEEP trial is a multi-centre, pragmatic, parallel group, individually randomised controlled trial, with embedded longitudinal qualitative interviews. 500 adults in primary care, aged 45 years and over with knee pain will be randomised to 1 of 3 treatment groups delivered by fully trained physiotherapists in up to 6 NHS services. These are: Usual Physiotherapy Care (control group consisting of up to 4 treatment sessions of advice and exercise), Individually Tailored Exercise (an individualised, supervised and progressed lower-limb exercise programme) or Targeted Exercise Adherence (supporting patients to adhere to exercise and to engage in general physical activity over the longer-term). The primary outcomes are pain and function as measured by the Western Ontario and McMaster Osteoarthritis index. A comprehensive range of secondary outcomes are also included. Outcomes are measured at 3, 6 (primary outcome time-point), 9, 18 and 36 months. Data on adverse events will also be collected. Semi-structured, qualitative interviews with a subsample of 30 participants (10 from each treatment group) will be undertaken at two time-points (end of treatment and 12 to 18 months later) and analysed thematically. This trial will contribute to the evidence base for management of older adults with knee pain attributable to osteoarthritis in primary care. The findings will have important implications for healthcare commissioners, general practitioners and physiotherapy service providers and it will inform future education of healthcare practitioners. It may also serve to delay or prevent some individuals from becoming surgical candidates. ISRCTN93634563.

Effectiveness of functional hand splinting and the cognitive orientation to occupational performance (CO-OP) approach in children with cerebral palsy and brain injury: two randomised controlled trial protocols

PubMed Central

2014-01-01

Background Cerebral palsy (CP) and brain injury (BI) are common conditions that have devastating effects on a child’s ability to use their hands. Hand splinting and task-specific training are two interventions that are often used to address deficits in upper limb skills, both in isolation or concurrently. The aim of this paper is to describe the method to be used to conduct two randomised controlled trials (RCT) investigating (a) the immediate effect of functional hand splints, and (b) the effect of functional hand splints used concurrently with task-specific training compared to functional hand splints alone, and to task-specific training alone in children with CP and BI. The Cognitive Orientation to Occupational Performance (CO-OP) approach will be the task-specific training approach used. Methods/Design Two concurrent trials; a two group, parallel design, RCT with a sample size of 30 participants (15 per group); and a three group, parallel design, assessor blinded, RCT with a sample size of 45 participants (15 per group). Inclusion criteria: age 4-15 years; diagnosis of CP or BI; Manual Abilities Classification System (MACS) level I – IV; hand function goals; impaired hand function; the cognitive, language and behavioural ability to participate in CO-OP. Participants will be randomly allocated to one of 3 groups; (1) functional hand splint only (n=15); (2) functional hand splint combined with task-specific training (n=15); (3) task-specific training only (n=15). Allocation concealment will be achieved using sequentially numbered, sealed opaque envelopes opened by an off-site officer after baseline measures. Treatment will be provided for a period of 2 weeks, with outcome measures taken at baseline, 1 hour after randomisation, 2 weeks and 10 weeks. The functional hand splint will be a wrist cock-up splint (+/- thumb support or supination strap). Task-specific training will involve 10 sessions of CO-OP provided in a group of 2-4 children. Primary outcome measures will be the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS). Analysis will be conducted on an intention-to-treat basis. Discussion This paper outlines the protocol for two randomised controlled trials investigating functional hand splints and CO-OP for children with CP and BI. PMID:25023385

Open three-stage transthoracic oesophagectomy versus minimally invasive thoraco-laparoscopic oesophagectomy for oesophageal cancer: protocol for a multicentre prospective, open and parallel, randomised controlled trial.

PubMed

Mu, Juwei; Gao, Shugeng; Mao, Yousheng; Xue, Qi; Yuan, Zuyang; Li, Ning; Su, Kai; Yang, Kun; Lv, Fang; Qiu, Bin; Liu, Deruo; Chen, Keneng; Li, Hui; Yan, Tiansheng; Han, Yongtao; Du, Ming; Xu, Rongyu; Wen, Zhaoke; Wang, Wenxiang; Shi, Mingxin; Xu, Quan; Xu, Shun; He, Jie

2015-11-17

Oesophageal cancer is the eighth most common cause of cancer worldwide. In 2009 in China, the incidence and death rate of oesophageal cancer was 22.14 per 100 000 person-years and 16.77 per 100 000 person-years, respectively, the highest in the world. Minimally invasive oesophagectomy (MIO) was introduced into clinical practice with the aim of reducing the morbidity rate. The mechanisms of MIO may lie in minimising the reaction to surgical injury and inflammation. There are some randomised trials regarding minimally invasive versus open oesophagectomy, with 100-850 subjects enrolled. To date, no large randomised controlled trial comparing minimally invasive versus open oesophagectomy has been reported in China, where squamous cell carcinoma predominated over adenocarcinoma of the oesophagus. This is a 3 year multicentre, prospective, randomised, open and parallel controlled trial, which aims to compare the effectiveness of minimally invasive thoraco-laparoscopic oesophagectomy to open three-stage transthoracic oesophagectomy for resectable oesophageal cancer. Group A patients receive MIO which involves thoracoscopic oesophagectomy and laparoscopic gastric mobilisation with cervical anastomosis. Group B patients receive the open three-stage transthoracic oesophagectomy which involves a right thoracotomy and laparotomy with cervical anastomosis. Primary endpoints include respiratory complications within 30 days after operation. The secondary endpoints include other postoperative complications, influences on pulmonary function, intraoperative data including blood loss, operative time, the number and location of lymph nodes dissected, and mortality in hospital, the length of hospital stay, total expenses in hospital, mortality within 30 days, survival rate after 2 years, postoperative pain, and health-related quality of life (HRQoL). Three hundred and twenty-four patients in each group will be needed and a total of 648 patients will finally be enrolled into the study. The study protocol has been approved by the Institutional Ethics Committees of all participating institutions. The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations. NCT02355249. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Pilot parallel randomised controlled trial of protective socks against usual care to reduce skin tears in high risk people: 'STOPCUTS'.

PubMed

Powell, Roy J; Hayward, Christopher J; Snelgrove, Caroline L; Polverino, Kathleen; Park, Linda; Chauhan, Rohan; Evans, Philip H; Byford, Rachel; Charman, Carolyn; Foy, Christopher J W; Pritchard, Colin; Kingsley, Andrew

2017-01-01

Skin tears are common in older adults and those taking steroids and warfarin. They are traumatic, often blunt injuries caused by oblique knocks to the extremities. The epidermis may separate from the dermis or both layers from underlying tissues leaving a skin flap or total loss of tissue, which is painful and prone to infection. 'Dermatuff™' knee-length socks containing Kevlar fibres (used in stab-proof vests and motorcyclists' clothing) aim to prevent skin tears. The acceptability of the socks and the feasibility of a randomised controlled trial (RCT) had not been explored. In this pilot parallel group RCT, 90 people at risk of skin-tear injury from Devon care homes and primary care were randomised to receive the socks or treatment as usual (TAU). The pilot aimed to estimate parameters to inform the design of a substantive trial and record professionals' views and participants' acceptability of the intervention and of study participation. Participants were randomised from July 2013 and followed up until February 2015. Community participants were easier to recruit than care homes residents but were 10 years younger on average and more active. To recruit 90 participants, 395 had to be approached overall as 77% were excluded or declined. Seventy-nine participants (88%) completed the trial and 27/44 (61%) wore the socks for 16 weeks. There were 31 skin tear injuries affecting 18 (20%) of the 90 participants. The TAU group received more injuries, more repeated episodes, and larger tears with greater severity. Common daily diary reasons for not wearing the socks included perceived warmth in hot weather or not being available (holiday, in hospital, bed rest). Resource use data were obtainable and indicated that sock wearing gave a reduction in treatment costs whilst well-completed questionnaires showed improvements in secondary outcomes. This pilot trial has successfully informed the design and conduct of a future definitive cost-effectiveness RCT. It would need to be conducted in primary care with 880 active at-risk, elderly patients (440 per arm). Skin tear incidence and quality of life (from EQ5D5L) over a 4-month period would be the primary and secondary outcomes respectively. ISRCTN, ISRCTN96565376.

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study.

PubMed

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-10-01

To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial.

PubMed

Santer, Miriam; Rumsby, Kate; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Chorozoglou, Maria; Wood, Wendy; Roberts, Amanda; Thomas, Kim S; Williams, Hywel C; Little, Paul

2015-11-01

Bath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking. Objectives To determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in children Pragmatic open 2-armed parallel group randomised controlled trial. General practitioner (GP) practices in England and Wales. Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale). Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only. Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective. This protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers. ISRCTN84102309. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Bath additives for the treatment of childhood eczema (BATHE): protocol for multicentre parallel group randomised trial

PubMed Central

Santer, Miriam; Rumsby, Kate; Ridd, Matthew J; Francis, Nick A; Stuart, Beth; Chorozoglou, Maria; Wood, Wendy; Roberts, Amanda; Thomas, Kim S; Williams, Hywel C; Little, Paul

2015-01-01

Introduction Bath emollients are widely prescribed for childhood eczema, yet evidence of their benefits over direct application of emollients is lacking. Objectives To determine the clinical and cost-effectiveness of adding bath emollient to the standard management of eczema in children Methods and analysis Design: Pragmatic open 2-armed parallel group randomised controlled trial. Setting: General practitioner (GP) practices in England and Wales. Participants: Children aged over 12 months and less than 12 years with eczema, excluding inactive or very mild eczema (5 or less on Nottingham Eczema Severity Scale). Interventions: Children will be randomised to either bath emollients plus standard eczema care or standard eczema care only. Outcome measures: Primary outcome is long-term eczema severity, measured by the Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Secondary outcomes include: number of eczema exacerbations resulting in healthcare consultations over 1 year; eczema severity over 1 year; disease-specific and generic quality of life; medication use and healthcare resource use; cost-effectiveness. Aiming to detect a mean difference between groups of 2.0 (SD 7.0) in weekly POEM scores over 16 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up, gives a total sample size of 423 children. We will use repeated measures analysis of covariance, or a mixed model, to analyse weekly POEM scores. We will control for possible confounders, including baseline eczema severity and child's age. Cost-effectiveness analysis will be carried out from a National Health Service (NHS) perspective. Ethics and dissemination This protocol was approved by Newcastle and North Tyneside 1 NRES committee 14/NE/0098. Follow-up will be completed in 2017. Findings will be disseminated to participants and carers, the public, dermatology and primary care journals, guideline developers and decision-makers. Trial registration number ISRCTN84102309. PMID:26525422

A parallel-group, randomised controlled trial of a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners: design and rationale.

PubMed

Lambert, Sylvie D; Girgis, Afaf; McElduff, Patrick; Turner, Jane; Levesque, Janelle V; Kayser, Karen; Mihalopoulos, Cathrine; Shih, Sophy T F; Barker, Daniel

2013-01-01

Coping skills training interventions have been found to be efficacious in helping both patients and their partners manage the physical and emotional challenges they face following a cancer diagnosis. However, many of these interventions are costly and not sustainable. To overcome these issues, a self-directed format is increasingly used. The efficacy of self-directed interventions for patients has been supported; however, no study has reported on the outcomes for their partners. This study will test the efficacy of Coping-Together-a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners. The proposed three-group, parallel, randomised controlled trial will recruit patients diagnosed in the past 4 months with breast, prostate, colorectal cancer or melanoma through their treating clinician. Patients and their partners will be randomised to (1) a minimal ethical care (MEC) condition-selected Cancer Council New South Wales booklets and a brochure for the Cancer Council Helpline, (2) Coping-Together generic-MEC materials, the six Coping-Together booklets and DVD, the Cancer Council Queensland relaxation audio CD and login to the Coping-Together website or (3) Coping-Together tailored-MEC materials, the Coping-Together DVD, the login to the website and only those Coping-Together booklet sections that pertain to their direct concerns. Anxiety (primary outcome), distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy and dyadic and individual coping will be assessed before receiving the study material (ie, baseline) and again at 3, 6 and 12 months postbaseline. Intention-to-treat and per protocol analysis will be conducted. This study has been approved by the relevant local area health and University ethics committees. Study findings will be disseminated not only through peer-reviewed publications and conference presentations but also through educational outreach visits, publication of lay research summaries in consumer newsletters and publications targeting clinicians. Australian New Zealand Clinical Trials Registry ACTRN12613000491763 (03/05/2013).

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab.

PubMed

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-03-01

To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary end points included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometrical mean ratio (GMR) of AUC inf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of C max was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUC inf and C max were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. EudraCT number 2012-000785-37; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728].

PubMed

Oldham, Nicola S; Wright, Nat M J; Adams, Clive E; Sheard, Laura; Tompkins, Charlotte N E

2004-04-29

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial.

PubMed

Heinrich, Henriette; Goetze, Oliver; Menne, Dieter; Iten, Peter X; Fruehauf, Heiko; Vavricka, Stephan R; Schwizer, Werner; Fried, Michael; Fox, Mark

2010-12-14

To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms. Randomised controlled crossover study. 20 healthy adults (14 men) aged 23-58. Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium (13)Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order. Cumulative percentage dose of (13)C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales). Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of (13)C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P<0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, -0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference -0.40, -0.01 to -0.79; P<0.046). No difference in dyspeptic symptoms was present. Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms. ClinicalTrials.gov NCT00943696.

Bioinformatics algorithm based on a parallel implementation of a machine learning approach using transducers

NASA Astrophysics Data System (ADS)

Roche-Lima, Abiel; Thulasiram, Ruppa K.

2012-02-01

Finite automata, in which each transition is augmented with an output label in addition to the familiar input label, are considered finite-state transducers. Transducers have been used to analyze some fundamental issues in bioinformatics. Weighted finite-state transducers have been proposed to pairwise alignments of DNA and protein sequences; as well as to develop kernels for computational biology. Machine learning algorithms for conditional transducers have been implemented and used for DNA sequence analysis. Transducer learning algorithms are based on conditional probability computation. It is calculated by using techniques, such as pair-database creation, normalization (with Maximum-Likelihood normalization) and parameters optimization (with Expectation-Maximization - EM). These techniques are intrinsically costly for computation, even worse when are applied to bioinformatics, because the databases sizes are large. In this work, we describe a parallel implementation of an algorithm to learn conditional transducers using these techniques. The algorithm is oriented to bioinformatics applications, such as alignments, phylogenetic trees, and other genome evolution studies. Indeed, several experiences were developed using the parallel and sequential algorithm on Westgrid (specifically, on the Breeze cluster). As results, we obtain that our parallel algorithm is scalable, because execution times are reduced considerably when the data size parameter is increased. Another experience is developed by changing precision parameter. In this case, we obtain smaller execution times using the parallel algorithm. Finally, number of threads used to execute the parallel algorithm on the Breezy cluster is changed. In this last experience, we obtain as result that speedup is considerably increased when more threads are used; however there is a convergence for number of threads equal to or greater than 16.

Effectiveness of recruitment to a smartphone-delivered nutrition intervention in New Zealand: analysis of a randomised controlled trial.

PubMed

Volkova, Ekaterina; Michie, Jo; Corrigan, Callie; Sundborn, Gerhard; Eyles, Helen; Jiang, Yannan; Mhurchu, Cliona Ni

2017-07-02

Delivery of interventions via smartphone is a relatively new initiative in public health, and limited evidence exists regarding optimal strategies for recruitment. We describe the effectiveness of approaches used to recruit participants to a smartphone-enabled nutrition intervention trial. Internet and social media advertising, mainstream media advertising and research team networks were used to recruit New Zealand adults to a fully automated smartphone-delivered nutrition labelling trial (no face-to-face visits were required). Recruitment of Māori and Pacific participants was a key focus and ethically relevant recruitment materials and approaches were used where possible. The effectiveness of recruitment strategies was evaluated using Google Analytics, monitoring of study website registrations and randomisations, and self-reported participant data. The cost of the various strategies and associations with participant demographics were assessed. Over a period of 13 months, there were 2448 registrations on the study website, and 1357 eligible individuals were randomised into the study (55%). Facebook campaigns were the most successful recruitment strategy overall (43% of all randomised participants) and for all ethnic groups (Māori 44%, Pacific 44% and other 43%). Significant associations were observed between recruitment strategy and age (p<0.001), household size (p<0.001), ethnicity (p<0.001), gender (p=0.005) and interest in healthy eating (p=0.022). Facebook campaigns resulted in the highest absolute numbers of study registrations and randomisations (966 and 584, respectively). Network strategies and Facebook campaigns cost least per randomised participant (NZ$4 and NZ$5, respectively), whereas radio advertising costs most (NZ$179 per participant). Internet and social media advertising were the most effective and least costly approaches to recruiting participants to a smartphone-delivered trial. These approaches also reached diverse ethnic groups. However, more culturally appropriate recruitment strategies are likely to be necessary in studies where large numbers of participants from specific ethnic groups are sought. ACTRN12614000644662; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. Trial registration number NCT02483351; Pre-results. PMID:27927658

Systematic Review of Integrative Health Care Research: Randomized Control Trials, Clinical Controlled Trials, and Meta-Analysis

DTIC Science & Technology

2010-01-01

to usual care (control). Also, in the pilot study of the 4 individual Noetic therapies, off-site prayer was associated with the lowest absolute...mortality in-hospital and at 6 months [16]. The parallel randomization to 4 different Noetic therapies across 5 study arms limited the assessment of...interventional cardiac care: the Monitoring and Actualisation of Noetic Trainings (MANTRA) II randomised study ,” Lancet, vol. 366, no. 9481, pp. 211–217, 2005. [18

Synthesis of Bipartite Tetracysteine PNA Probes for DNA In Situ Fluorescent Labeling.

PubMed

Fang, Ge-Min; Seitz, Oliver

2017-12-24

"Label-free" fluorescent probes that avoid additional steps or building blocks for conjugation of fluorescent dyes with oligonucleotides can significantly reduce the time and cost of parallel bioanalysis of a large number of nucleic acid samples. A method for the synthesis of "label-free" bicysteine-modified PNA probes using solid-phase synthesis and procedures for sequence-specific DNA in situ fluorescent labeling is described here. The concept is based on the adjacent alignment of two bicysteine-modified peptide nucleic acids on a DNA target to form a structurally optimized bipartite tetracysteine motif, which induces a sequence-specific fluorogenic reaction with commercially available biarsenic dyes, even in complex media such as cell lysate. This unit will help researchers to quickly synthesize bipartite tetracysteine PNA probes and carry out low-cost DNA in situ fluorescent labeling experiments. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

HCG-. beta. -subunit radioimmunoassay: potential error in HCG measurement related to choice of labeled antigen. [/sup 125/I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyrey, L.; Hammond, C.B.

1976-05-15

Antiserum generated against the hormone-specific ..beta..-subunit of hCG was used with different labeled antigens to measure circulating hCG in patients having trophoblastic disease. When /sup 125/I-hCG..beta.. served as the labeled antigen, a small number of patient sera failed to show parallelism with the second IS-hCG reference and erroneous estimates of hormone concentrations were obtained. Replacement of the /sup 125/I-hCG..beta.. with labeled hCG corrected the nonparallelism exhibited by these samples. Inhibition curves obtained with purified hCG and hCG..beta.. suggested that both the nonparallelism and its correction with the change in labeled antigen would be consistent with the possibility that this assaymore » aberration may result from the presence of free hCG..beta.. in these sera. (auth)« less

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial.

PubMed

Waddell, Tom; Chau, Ian; Cunningham, David; Gonzalez, David; Okines, Alicia Frances Clare; Frances, Alicia; Okines, Clare; Wotherspoon, Andrew; Saffery, Claire; Middleton, Gary; Wadsley, Jonathan; Ferry, David; Mansoor, Wasat; Crosby, Tom; Coxon, Fareeda; Smith, David; Waters, Justin; Iveson, Timothy; Falk, Stephen; Slater, Sarah; Peckitt, Clare; Barbachano, Yolanda

2013-05-01

EGFR overexpression occurs in 27-55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 1-21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 1-21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade ≥ 3 neutropenia 35 [13%] vs 74 [28%]). Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. Amgen, UK National Institute for Health Research Biomedical Research Centre. Copyright © 2013 Elsevier Ltd. All rights reserved.

Decision peptide-driven: a free software tool for accurate protein quantification using gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry.

PubMed

Santos, Hugo M; Reboiro-Jato, Miguel; Glez-Peña, Daniel; Nunes-Miranda, J D; Fdez-Riverola, Florentino; Carvallo, R; Capelo, J L

2010-09-15

The decision peptide-driven tool implements a software application for assisting the user in a protocol for accurate protein quantification based on the following steps: (1) protein separation through gel electrophoresis; (2) in-gel protein digestion; (3) direct and inverse (18)O-labeling and (4) matrix assisted laser desorption ionization time of flight mass spectrometry, MALDI analysis. The DPD software compares the MALDI results of the direct and inverse (18)O-labeling experiments and quickly identifies those peptides with paralleled loses in different sets of a typical proteomic workflow. Those peptides are used for subsequent accurate protein quantification. The interpretation of the MALDI data from direct and inverse labeling experiments is time-consuming requiring a significant amount of time to do all comparisons manually. The DPD software shortens and simplifies the searching of the peptides that must be used for quantification from a week to just some minutes. To do so, it takes as input several MALDI spectra and aids the researcher in an automatic mode (i) to compare data from direct and inverse (18)O-labeling experiments, calculating the corresponding ratios to determine those peptides with paralleled losses throughout different sets of experiments; and (ii) allow to use those peptides as internal standards for subsequent accurate protein quantification using (18)O-labeling. In this work the DPD software is presented and explained with the quantification of protein carbonic anhydrase. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Flexible-rate optical packet generation/detection and label swapping for optical label switching networks

NASA Astrophysics Data System (ADS)

Wu, Zhongying; Li, Juhao; Tian, Yu; Ge, Dawei; Zhu, Paikun; Chen, Yuanxiang; Chen, Zhangyuan; He, Yongqi

2017-03-01

In recent years, optical label switching (OLS) gains lots of attentions due to its intrinsic advantages to implement protocol, bit-rate, granularity and data format transparency packet switching. In this paper, we propose a novel scheme to realize flexible-rate optical packet switching for OLS networks. At the transmitter node, flexible-rate packet is generated by parallel modulating different combinations of optical carriers generated from the optical multi-carrier generator (OMCG), among which the low-speed optical label occupies one carrier. At the switching node, label is extracted and re-generated in label processing unit (LPU). The payloads are switched based on routing information and new label is added after switching. At the receiver node, another OMCG serves as local oscillators (LOs) for optical payloads coherent detection. The proposed scheme offers good flexibility for dynamic optical packet switching by adjusting the payload bandwidth and could also effectively reduce the number of lasers, modulators and receivers for packet generation/detection. We present proof-of-concept demonstrations of flexible-rate packet generation/detection and label swapping in 12.5 GHz grid. The influence of crosstalk for cascaded label swapping is also investigated.

Study protocol: can a school gardening intervention improve children's diets?

PubMed

Christian, Meaghan S; El Evans, Charlotte; Conner, Mark; Ransley, Joan K; Cade, Janet E

2012-04-26

The current academic literature suggests there is a potential for using gardening as a tool to improve children's fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children's fruit and vegetable intake. Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as "Partner Schools" and the other to receive the less intensive intervention as "Associate Schools". Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention "Associate Schools" or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children's knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school's gardening activities. The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children's fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children's diets and school based interventions. ISRCTN11396528.

So you want to conduct a randomised trial? Learnings from a 'failed' feasibility study of a Crisis Resource Management prompt during simulated paediatric resuscitation.

PubMed

Teis, Rachel; Allen, Jyai; Lee, Nigel; Kildea, Sue

2017-02-01

No study has tested a Crisis Resource Management prompt on resuscitation performance. We conducted a feasibility, unblinded, parallel-group, randomised controlled trial at one Australian paediatric hospital (June-September 2014). Eligible participants were any doctor, nurse, or nurse manager who would normally be involved in a Medical Emergency Team simulation. The unit of block randomisation was one of six scenarios (3 control:3 intervention) with or without a verbal prompt. The primary outcomes tested the feasibility and utility of the intervention and data collection tools. The secondary outcomes measured resuscitation quality and team performance. Data were analysed from six resuscitation scenarios (n=49 participants); three control groups (n=25) and three intervention groups (n=24). The ability to measure all data items on the data collection tools was hindered by problems with the recording devices both in the mannequins and the video camera. For a pilot study, greater training for the prompt role and pre-briefing participants about assessment of their cardio-pulmonary resuscitation quality should be undertaken. Data could be analysed in real time with independent video analysis to validate findings. Two cameras would strengthen reliability of the methods. Copyright © 2016 College of Emergency Nursing Australasia. Published by Elsevier Ltd. All rights reserved.

Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.

PubMed

Lockley, Steven W; Dressman, Marlene A; Licamele, Louis; Xiao, Changfu; Fisher, Dennis M; Flynn-Evans, Erin E; Hull, Joseph T; Torres, Rosarelis; Lavedan, Christian; Polymeropoulos, Mihael H

2015-10-31

Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist. We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres. We screened totally blind adults (18-75 years of age), who were eligible for the randomisation phase of SET if they had a non-24-hour circadian period (τ) of 24·25 h or longer (95% CI greater than 24·0 and up to 24·9 h), as calculated from measurements of urinary 6-sulphatoxymelatonin rhythms. For SET, we used block randomisation to assign patients (1:1) to receive tasimelteon (20 mg) or placebo every 24 h at a fixed clock time 1 h before target bedtime for 26 weeks. Patients who entered the open-label group receiving tasimelteon in SET or who did not meet the SET inclusion criteria but did meet the RESET inclusion criteria were screened for RESET. A subset of the patients who entered the open-label group before the RESET study and who had eligible τ values were screened for RESET after completing the open-label treatment. In RESET, we withdrew tasimelteon in a randomised manner (1:1) in patients who responded (ie, entrained) after a tasimelteon run-in period. Entrainment was defined as having τ of 24·1 h or less and a 95% CI that included 24·0 h. In SET, the primary endpoint was the proportion of entrained patients, assessed in the intention-to-treat population. The planned step-down primary endpoint assessed the proportion of patients who had a clinical response (entrainment at month 1 or month 7 plus clinical improvement, measured by the Non-24 Clinical Response Scale). In RESET, the primary endpoint was the proportion of non-entrained patients, assessed in the intention-to-treat population. Safety assessments included adverse events and clinical laboratory measures, assessed in all treated patients. These trials are registered with ClinicalTrials.gov, numbers NCT01163032 and NCT01430754. Between Aug 25, 2010, and July 5, 2012, we screened 391 totally blind patients for SET, of whom 84 (22%) were assigned to receive tasimelteon (n=42) or placebo (n=42). Two patients in the tasimelteon group and four in the placebo group discontinued the study before τ was measured, due to adverse events, withdrawal of consent, and a protocol deviation. Circadian entrainment occurred in eight (20%) of 40 patients in the tasimelteon group compared with one (3%) of 38 patients in the placebo group at month 1 (difference 17%, 95% CI 3·2-31·6; p=0·0171). Nine (24%) of 38 patients showed a clinical response, compared with none of 34 in the placebo group (difference 24%, 95% CI 8·4-39·0; p=0·0028). Between Sept 15, 2011, and Oct 4, 2012, we screened 58 patients for eligibility in RESET, 48 (83%) of whom had τ assessed and entered the open-label tasimelteon run-in phase. 24 (50%) patients entrained, and 20 (34%) were enrolled in the randomisation phase. Two (20%) of ten patients who were withdrawn to placebo remained entrained compared with nine (90%) of ten who continued to receive tasimelteon (difference 70%, 95% CI 26·4-100·0; p=0·0026). No deaths were reported in either study, and discontinuation rates due to adverse events were comparable between the tasimelteon (3 [6%] of 52 patients) and placebo (2 [4%] of 52 patients) treatment courses. The most common side-effects associated with tasimelteon in SET were headache (7 [17%] of 42 patients given tasimelteon vs 3 [7%] of 42 patients given placebo), elevated liver enzymes (4 [10%] vs 2 [5%]), nightmares or abnormal dreams (4 [10%] vs none), upper respiratory tract infection (3 [7%] vs none], and urinary tract infections (3 [7%] vs 1 [2%]). Once-daily tasimelteon can entrain totally blind people with non-24; however, continued tasimelteon treatment is necessary to maintain these improvements. Vanda Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial.

PubMed

Hollands, Kristen L; Pelton, Trudy A; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M; Wing, Alan M; Tyson, Sarah F; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M

2015-01-01

Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services. Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments. Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Clinicaltrials.gov NCT01600391.

Comments on Samal and Henderson: Parallel consistent labeling algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swain, M.J.

Samal and Henderson claim that any parallel algorithm for enforcing arc consistency in the worst case must have {Omega}(na) sequential steps, where n is the number of nodes, and a is the number of labels per node. The authors argue that Samal and Henderon's argument makes assumptions about how processors are used and give a counterexample that enforces arc consistency in a constant number of steps using O(n{sup 2}a{sup 2}2{sup na}) processors. It is possible that the lower bound holds for a polynomial number of processors; if such a lower bound were to be proven it would answer an importantmore » open question in theoretical computer science concerning the relation between the complexity classes P and NC. The strongest existing lower bound for the arc consistency problem states that it cannot be solved in polynomial log time unless P = NC.« less

Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation

PubMed Central

Bensdorp, A J; Tjon-Kon-Fat, R I; Bossuyt, P M M; Koks, C A M; Oosterhuis, G J E; Hoek, A; Hompes, P G A; Broekmans, F J M; Verhoeve, H R; de Bruin, J P; van Golde, R; Repping, S; Cohlen, B J; Lambers, M D A; van Bommel, P F; Slappendel, E; Perquin, D; Smeenk, J M; Pelinck, M J; Gianotten, J; Hoozemans, D A; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W J

2015-01-01

Objectives To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child. Design Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial. Setting 17 centres in the Netherlands. Participants Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility. Interventions Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation. Main outcome measures The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality Results 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation). Conclusions In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates. Trial registration Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939. PMID:25576320

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection’s severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. Methods We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. Discussion This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored. Trial registration Current Controlled Trial ISRCTN 37666216 PMID:23249501

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial.

PubMed

Thwaites, Guy; Auckland, Cressida; Barlow, Gavin; Cunningham, Richard; Davies, Gerry; Edgeworth, Jonathan; Greig, Julia; Hopkins, Susan; Jeyaratnam, Dakshika; Jenkins, Neil; Llewelyn, Martin; Meisner, Sarah; Nsutebu, Emmanuel; Planche, Tim; Read, Robert C; Scarborough, Matthew; Soares, Marta; Tilley, Robert; Török, M Estée; Williams, John; Wilson, Peter; Wyllie, Sarah; Walker, A Sarah

2012-12-18

Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection's severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥ 18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤ 96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900 mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored.

Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials.

PubMed

Tattersall, Martin H N; Jefford, Michael; Martin, Andrew; Olver, Ian; Thompson, John F; Brown, Richard F; Butow, Phyllis N

2017-03-01

To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials. Tertiary cancer referral hospitals in three state capital cities in Australia. 88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial. We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial. Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. scores on the Quality of Informed Consent questionnaire (QuIC). 88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups. Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006. Results, ACTRN12606000214538. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A pilot randomised double blind controlled trial of the efficacy of purified fatty acids for the treatment of women with endometriosis-associated pain (PurFECT): study protocol.

PubMed

Abokhrais, Ibtisam M; Saunders, Philippa T K; Denison, Fiona C; Doust, Ann; Williams, Linda; Horne, Andrew W

2018-01-01

Endometriosis affects 6-10% of women and is associated with debilitating pelvic pain. It costs the UK > £2.8 billion per year in loss of productivity. Endometriosis can be managed by surgical excision or medically by ovarian suppression. However, ~ 75% symptoms recur after surgery and available medical treatments have undesirable side effects and are contraceptive. Omega-3 purified fatty acids (PUFA) have been shown in animal models to reduce factors that are thought to lead to endometriosis-associated pain, have minimal side effects, and no effects on fertility. This paper presents a protocol for a two-arm, pilot parallel randomised controlled trial (RCT) which aims to inform the planning of a future multicentre trial to evaluate the efficacy of Omega-3 PUFA in the management of endometriosis-associated pain in women. The study will recruit women with endometriosis over a 12-month period in the National Health Service (NHS) Lothian, UK, and randomise them to 8 weeks of treatment with Omega-3 PUFA or comparator (olive oil). The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness/acceptability to participants of the proposed methods of recruitment/randomisation/treatments/questionnaires, to inform the sample size calculation and to refine the research methodology for a future large randomised controlled trial. Response to treatment will be monitored by pain scores and questionnaires assessing physical and emotional function compared at baseline and 8 weeks. We recognise that there may be potential difficulties in mounting a large randomised controlled trial for endometriosis to assess Omega-3 PUFA because they are a dietary supplement readily available over the counter and already used by women with endometriosis. We have therefore designed this pilot study to assess practical feasibility and following the 'Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials' recommendations for the design of chronic pain trials. ISRCTN44202346.

Parallel, confocal, and complete spectrum imager for fluorescent detection of high-density microarray

NASA Astrophysics Data System (ADS)

Bogdanov, Valery L.; Boyce-Jacino, Michael

1999-05-01

Confined arrays of biochemical probes deposited on a solid support surface (analytical microarray or 'chip') provide an opportunity to analysis multiple reactions simultaneously. Microarrays are increasingly used in genetics, medicine and environment scanning as research and analytical instruments. A power of microarray technology comes from its parallelism which grows with array miniaturization, minimization of reagent volume per reaction site and reaction multiplexing. An optical detector of microarray signals should combine high sensitivity, spatial and spectral resolution. Additionally, low-cost and a high processing rate are needed to transfer microarray technology into biomedical practice. We designed an imager that provides confocal and complete spectrum detection of entire fluorescently-labeled microarray in parallel. Imager uses microlens array, non-slit spectral decomposer, and high- sensitive detector (cooled CCD). Two imaging channels provide a simultaneous detection of localization, integrated and spectral intensities for each reaction site in microarray. A dimensional matching between microarray and imager's optics eliminates all in moving parts in instrumentation, enabling highly informative, fast and low-cost microarray detection. We report theory of confocal hyperspectral imaging with microlenses array and experimental data for implementation of developed imager to detect fluorescently labeled microarray with a density approximately 103 sites per cm2.

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

A Bioluminometric Method of DNA Sequencing

NASA Technical Reports Server (NTRS)

Ronaghi, Mostafa; Pourmand, Nader; Stolc, Viktor; Arnold, Jim (Technical Monitor)

2001-01-01

Pyrosequencing is a bioluminometric single-tube DNA sequencing method that takes advantage of co-operativity between four enzymes to monitor DNA synthesis. In this sequencing-by-synthesis method, a cascade of enzymatic reactions yields detectable light, which is proportional to incorporated nucleotides. Pyrosequencing has the advantages of accuracy, flexibility and parallel processing. It can be easily automated. Furthermore, the technique dispenses with the need for labeled primers, labeled nucleotides and gel-electrophoresis. In this chapter, the use of this technique for different applications is discussed.

The absorption of vitamin E is influenced by the amount of fat in a meal and the food matrix.

PubMed

Jeanes, Yvonne M; Hall, Wendy L; Ellard, Susan; Lee, Elizabeth; Lodge, John K

2004-10-01

Vitamin E absorption requires the presence of fat; however, limited information exists on the influence of fat quantity on optimal absorption. In the present study we compared the absorption of stable-isotope-labelled vitamin E following meals of varying fat content and source. In a randomised four-way cross-over study, eight healthy individuals consumed a capsule containing 150 mg (2)H-labelled RRR-alpha-tocopheryl acetate with a test meal of toast with butter (17.5 g fat), cereal with full-fat milk (17.5 g fat), cereal with semi-skimmed milk (2.7 g fat) and water (0 g fat). Blood was taken at 0, 0.5, 1, 1.5, 2, 3, 6 and 9 h following ingestion, chylomicrons were isolated, and (2)H-labelled alpha-tocopherol was analysed in the chylomicron and plasma samples. There was a significant time (P<0.001) and treatment effect (P<0.001) in (2)H-labelled alpha-tocopherol concentration in both chylomicrons and plasma between the test meals. (2)H-labelled alpha-tocopherol concentration was significantly greater with the higher-fat toast and butter meal compared with the low-fat cereal meal or water (P<0.001), and a trend towards greater concentration compared with the high-fat cereal meal (P=0.065). There was significantly greater (2)H-labelled alpha-tocopherol concentration with the high-fat cereal meal compared with the low-fat cereal meal (P<0.05). The (2)H-labelled alpha-tocopherol concentration following either the low-fat cereal meal or water was low. These results demonstrate that both the amount of fat and the food matrix influence vitamin E absorption. These factors should be considered by consumers and for future vitamin E intervention studies.

Effects on abstinence of nicotine patch treatment before quitting smoking: parallel, two arm, pragmatic randomised trial.

PubMed

2018-06-13

To examine the effectiveness of a nicotine patch worn for four weeks before a quit attempt. Randomised controlled open label trial. Primary care and smoking cessation clinics in England, 2012-15. 1792 adults who were daily smokers with tobacco dependence. 899 were allocated to the preloading arm and 893 to the control arm. Participants were randomised 1:1, using concealed randomly permuted blocks stratified by centre, to either standard smoking cessation pharmacotherapy and behavioural support or the same treatment supplemented by four weeks of 21 mg nicotine patch use before quitting: "preloading." The primary outcome was biochemically confirmed prolonged abstinence at six months. Secondary outcomes were prolonged abstinence at four weeks and 12 months. Biochemically validated abstinence at six months was achieved by 157/899 (17.5%) participants in the preloading arm and 129/893 (14.4%) in the control arm: difference 3.0% (95% confidence interval -0.4% to 6.4%), odds ratio 1.25 (95% confidence interval 0.97 to 1.62), P=0.08 in the primary analysis. There was an imbalance between arms in the frequency of varenicline use as post-cessation treatment, and planned adjustment for this gave an odds ratio for the effect of preloading of 1.34 (95% confidence interval 1.03 to 1.73), P=0.03: difference 3.8% (0.4% to 7.2%). At four weeks, the difference in prolonged abstinence unadjusted for varenicline use was odds ratio 1.21 (1.00 to 1.48), difference 4.3% (0.0% to 8.7%), P=0.05, and adjusted for varenicline use was 1.32 (1.08 to 1.62) P=0.007. At 12 months the odds ratio was 1.28 (0.97 to 1.69), difference 2.7% (-0.4% to 5.8%), P=0.09 unadjusted for varenicline use and after adjustment was 1.36 (1.02 to 1.80) P=0.04. 5.9% of participants discontinued preloading owing to intolerance. Gastrointestinal symptoms-chiefly nausea-occurred in 4.0% (2.2% to 5.9%) more people in the preloading arm than control arm. Eight serious adverse events occurred in the preloading arm and eight in the control arm (odds ratio 0.99, 0.36 to 2.75). Evidence was insufficient to confidently show that nicotine preloading increases subsequent smoking abstinence. The beneficial effect seems to have been masked by a concurrent reduction in the use of varenicline in people using nicotine preloading, and future studies should explore ways to mitigate this unintended effect. Current Controlled Trials ISRCTN33031001. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of wet-cupping therapy for persistent non-specific low back pain: a randomised, waiting-list controlled, open-label, parallel-group pilot trial

PubMed Central

2011-01-01

Background Persistent non-specific low back pain (PNSLBP) is one of the most frequently experienced types of back pain around the world. Wet-cupping is a common intervention for various pain conditions, especially in Korea. In this context, we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP. Methods We recruited 32 participants (21 in the wet-cupping group and 11 in the waiting-list group) who had been having PNSLBP for at least 3 months. The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine, Korea. Eligible participants were randomly allocated to wet-cupping and waiting-list groups. Following the practice of traditional Korean medicine, the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23, BL24 and BL25 6 times within 2 weeks. Usual care, including providing brochures for exercise, general advice for PNSLBP and acetaminophen, was allowed in both groups. Separate assessors participated in the outcome assessment. We used the 0 to100 numerical rating scale (NRS) for pain, the McGill Pain Questionnaire for pain intensity (PPI) and the Oswestry Disability Questionnaire (ODQ), and we assessed acetaminophen use and safety issues. Results The results showed that the NRS score for pain decreased (-16.0 [95% CI: -24.4 to -7.7] in the wet-cupping group and -9.1 [-18.1 to -0.1] in the waiting-list group), but there was no statistical difference between the groups (p = 0.52). However, the PPI scores showed significant differences between the two groups (-1.2 [-1.6 to -0.8] for the wet-cupping group and -0.2 [-0.8 to 0.4] for the waiting-list group, p < 0.01). In addition, less acetaminophen was used in the wet-cupping group during 4 weeks (p = 0.09). The ODQ score did not show significant differences between the two groups (-5.60 [-8.90 to -2.30] in the wet-cupping group and -1.8 [-5.8 to 2.2] in the waiting-list group, p = 0.14). There was no report of adverse events due to wet-cupping. Conclusion This pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP. Future full-scale randomised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention. Trial Registration ClinicalTrials.gov: (Identifier: NCT00925951) Date of trial registration: June 19th, 2009 The date when the first patient was randomised: July 15th, 2009 The date when the study was completed: November 27th, 2009 PMID:21663617

Pressure ulcers prevention efficacy of an alternating pressure air mattress in elderly patients: E²MAO a randomised study.

PubMed

Sauvage, P; Touflet, M; Pradere, C; Portalier, F; Michel, J-M; Charru, P; Passadori, Y; Fevrier, R; Hallet-Lezy, A-M; Beauchêne, F; Scherrer, B

2017-06-02

Our aim was to compare Axtair One, an alternating pressure air mattress (APAM), with a viscoelastic foam mattress (VFM) in elderly patients at moderate to high risk of developing pressure ulcers (PUs). A randomised, controlled, superiority, parallel-group, open-label, multicentre study, was conducted, between February 2012 and March 2015, in nine French, medium- and long-term stay facilities. Eligible patients were aged 70 and over, had no PUs on enrolment, were bedridden for at least 15 hours per day, had reduced mobility, an absent or minimal positioning capability, a Braden score <14, a nutritional status score >12 and a Karnofsky score <40%. The primary endpoint was the appearance of PUs over a 30-day monitoring period. The primary objective was to demonstrate a 50% reduction in instantaneous risk of PUs in the APAM versus the VFM group. Secondary objectives were to determine if preventive care was less frequent in the APAM group, the instantaneous relative risk of PUs (hazard ratio) was constant over time and the comfort experienced was higher in the APAM group and to verify the uniformity of the preventive benefit of an APAM, regardless of the level of exposure to major risk factors for PUs. We randomised 76 patients (39 in the APAM group and 37 in the VFM group). The groups were comparable on enrolment and throughout the study. The cumulative risk of PUs was estimated at 6.46% [95% confidence interval (CI): 1.64; 23.66] in the APAM group and at 38.91% [95% CI: 24.66; 57.59] in the VFM group, p=0.001 (log-rank test). The adjusted hazard ratio according to the Cox model with four prognostic factors for the appearance of PUs was 7.57 [95% CI: 1.67; 34.38, p=0.009]. Preventive care proved to be equivalent in both groups. The only risk factor significantly associated with an increased risk of PUs was the type of mattress (VFM). The comfort and tolerance perceived by the patients were both high and similar in the two groups. The constancy over time of the preventive benefit of an APAM could not be verified because of the lack of a sufficient number of events (appearance of PUs) in the APAM group. The APAM was superior to a VFM for preventing PUs in elderly patients, bedridden for more than 15 hours per day, severely dependent, at moderate-to high-risk of PUs, with an instantaneous risk for the appearance of PUs 7.57 times greater in the VFM group than in the APAM group. This study provides descriptive information and evidence for practice.

Design and rationale of the ATHENA study--A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial.

PubMed

Sommerer, Claudia; Suwelack, Barbara; Dragun, Duska; Schenker, Peter; Hauser, Ingeborg A; Nashan, Björn; Thaiss, Friedrich

2016-02-17

Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3-8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3-8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact. Clinicaltrials.gov: NCT01843348, date of registration--18 April 2013; EUDRACT number: 2011-005238-21, date of registration--20 March 2012.

Influence of the antiseptic agents polyhexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study.

PubMed

Kramer, A; Roth, B; Müller, G; Rudolph, P; Klöcker, N

2004-01-01

The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells. Copyright 2004 S. Karger AG, Basel

Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial.

PubMed

Goette, Andreas; Merino, Jose L; Ezekowitz, Michael D; Zamoryakhin, Dmitry; Melino, Michael; Jin, James; Mercuri, Michele F; Grosso, Michael A; Fernandez, Victor; Al-Saady, Naab; Pelekh, Natalya; Merkely, Bela; Zenin, Sergey; Kushnir, Mykola; Spinar, Jindrich; Batushkin, Valeriy; de Groot, Joris R; Lip, Gregory Y H

2016-10-22

Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available. We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin-warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)-stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region-was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with ClinicalTrials.gov, number NCT02072434. Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin-warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA 2 DS 2 -VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin-warfarin group (odds ratio [OR] 0·46, 95% CI 0·12-1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin-warfarin (OR 1·48, 95% CI 0·64-3·55). The results were independent of the TEE-guided strategy and anticoagulation status. ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups. Daiichi Sankyo provided financial support for the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial.

PubMed

Schöffski, Patrick; Chawla, Sant; Maki, Robert G; Italiano, Antoine; Gelderblom, Hans; Choy, Edwin; Grignani, Giovanni; Camargo, Veridiana; Bauer, Sebastian; Rha, Sun Young; Blay, Jean-Yves; Hohenberger, Peter; D'Adamo, David; Guo, Matthew; Chmielowski, Bartosz; Le Cesne, Axel; Demetri, George D; Patel, Shreyaskumar R

2016-04-16

A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control). We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1·4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue. Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13·5 months [95% CI 10·9-15·6] vs 11·5 months [9·6-13·0]; hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators. Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma. Eisai. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial.

PubMed

Guery, Benoit; Menichetti, Francesco; Anttila, Veli-Jukka; Adomakoh, Nicholas; Aguado, Jose Maria; Bisnauthsing, Karen; Georgopali, Areti; Goldenberg, Simon D; Karas, Andreas; Kazeem, Gbenga; Longshaw, Chris; Palacios-Fabrega, Jose Alejandro; Cornely, Oliver A; Vehreschild, Maria J G T

2018-03-01

Clostridium difficile infection causes severe complications and frequently recurs. An extended-pulsed fidaxomicin regimen might facilitate sustained clinical cure by prolonging C difficile suppression and supporting gut microbiota recovery. We aimed to compare clinical outcomes of extended-pulsed fidaxomicin with standard vancomycin. In this randomised, controlled, open-label, superiority study, we recruited hospitalised adults aged 60 years and older with confirmed C difficile infection at 86 European hospitals. Patients were randomly assigned (1:1) using an interactive web response system to receive extended-pulsed fidaxomicin (200 mg oral tablets, twice daily on days 1-5, then once daily on alternate days on days 7-25) or vancomycin (125 mg oral capsules, four times daily on days 1-10), stratified by baseline C difficile infection severity, cancer presence, age (≥75 years vs <75 years), and number of previous C difficile infection occurrences. The primary endpoint was sustained clinical cure 30 days after end of treatment (day 55 for extended-pulsed fidaxomicin and day 40 for vancomycin), assessed in all randomised patients who met the inclusion criteria and received at least one dose of study medication (modified full analysis set). Adverse events were assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov, number NCT02254967. Between Nov 6, 2014, and May 5, 2016, 364 patients were enrolled and randomly assigned to receive extended-pulsed fidaxomicin or vancomycin. 362 patients received at least one dose of study medication (181 in each group). 124 (70%) of 177 patients in the modified full analysis set receiving extended-pulsed fidaxomicin achieved sustained clinical cure 30 days after end of treatment, compared with 106 (59%) of 179 patients receiving vancomycin (difference 11% [95% CI 1·0-20·7], p=0·030; odds ratio 1·62 [95% CI 1·04-2·54]). Incidence of treatment-emergent adverse events did not differ between extended-pulsed fidaxomicin (121 [67%] of 181) and vancomycin (128 [71%] of 181) treatment arms. One death in the vancomycin arm was considered by the investigator to be related to study drug. Extended-pulsed fidaxomicin was superior to standard-dose vancomycin for sustained cure of C difficile infection, and, to our knowledge, extended-pulsed fidaxomicin recurrence rates in this study are the lowest observed in a randomised clinical trial of antibiotic treatment for C difficile infection. Astellas Pharma, Inc. Copyright © 2018 Elsevier Ltd. All rights reserved.

Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial.

PubMed

Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Arance, Ana; Dutriaux, Caroline; Di Giacomo, Anna Maria; Rutkowski, Piotr; Del Vecchio, Michele; Gutzmer, Ralf; Mandala, Mario; Thomas, Luc; Demidov, Lev; Garbe, Claus; Hogg, David; Liszkay, Gabriella; Queirolo, Paola; Wasserman, Ernesto; Ford, James; Weill, Marine; Sirulnik, L Andres; Jehl, Valentine; Bozón, Viviana; Long, Georgina V; Flaherty, Keith

2017-04-01

There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m 2 intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01763164 and with EudraCT, number 2012-003593-51. Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4-4·1). Median progression-free survival was 2·8 months (95% CI 2·8-3·6) in the binimetinib group and 1·5 months (1·5-1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47-0·80]; one-sided p<0·001). Grade 3-4 adverse events seen in at least 5% of patients the safety population in either group were increased creatine phosphokinase (52 [19%] of 269 patients in the binimetinib group vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25 (22%) patients in the dacarbazine group. Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy. Array BioPharma and Novartis Pharmaceuticals Corporation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial.

PubMed

Aujesky, Drahomir; Roy, Pierre-Marie; Verschuren, Franck; Righini, Marc; Osterwalder, Joseph; Egloff, Michael; Renaud, Bertrand; Verhamme, Peter; Stone, Roslyn A; Legall, Catherine; Sanchez, Olivier; Pugh, Nathan A; N'gako, Alfred; Cornuz, Jacques; Hugli, Olivier; Beer, Hans-Jürg; Perrier, Arnaud; Fine, Michael J; Yealy, Donald M

2011-07-02

Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care. We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2-4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital ≤24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542. Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0·6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2·7%; p=0·011). Only one (0·6%) patient in each treatment group died within 90 days (95% UCL 2·1%; p=0·005), and two (1·2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3·6%; p=0·031). By 90 days, three (1·8%) outpatients but no inpatients had developed major bleeding (95% UCL 4·5%; p=0·086). Mean length of stay was 0·5 days (SD 1·0) for outpatients and 3·9 days (SD 3·1) for inpatients. In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care. Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres. Copyright © 2011 Elsevier Ltd. All rights reserved.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Homeopathy for Perennial Asthma in Adolescents: Pilot Feasibility Study Testing a Randomised Withdrawal Design.

PubMed

Mitchiguian Hotta, Livia; Cardinalli Adler, Ubiratan; de Toledo Cesar, Amarilys; Martinez, Edson Zangiacomi; Demarzo, Marcelo Marcos Piva

2018-05-01

 Previous findings from a pragmatic trial suggest that usual care compared with usual care plus individualised homeopathy is not a feasible design to address homeopathic interventions for asthma.  The main purpose of this article was to investigate the feasibility of the randomised withdrawal design as a strategy to assess the effectiveness of a standardised clinical-pharmaceutical homeopathic protocol ( Organon.modus ) on perennial asthma in adolescents.  Randomised withdrawal, double-blind, parallel, placebo-controlled, 12-week study. 12 to 17 years old adolescents, with the diagnosis of perennial asthma, using inhalatory beclomethasone (plus fenoterol for wheezing episodes), who achieved 3 months of well-controlled asthma, after a variable period of individualised homeopathic treatment according to Organon.modus protocol. a secondary care medical specialist centre. continuation with the individualised homeopathic medicine or with indistinguishable placebo during 12 weeks of beclomethasone step-down. number of days of well-controlled asthma. Secondary measures: number of days of fenoterol use, number of visits to an emergency service (without hospitalisation) and percentage of patients excluded due to an exacerbation characterising a partly controlled asthma. Tolerability was assessed by Adverse Events, registered at every visit.  Nineteen patients were randomised to continue treatment with homeopathy and 21 with placebo. Effectiveness measures for the homeopathy and placebo groups respectively were median number of days of good clinical control: 84 versus 30 ( p  = 0.18); median number of days of fenoterol use per patient: 3 versus 5 ( p  = 0.41); visits to an emergency room: 1 versus 6 ( p  = 0.35); percentage of exclusion due to partly controlled asthma: 36.8% versus 71.4% ( p  = 0.05). Few Adverse Events were reported.  This pilot study supports the feasibility of the double-blind randomised withdrawal design in studies investigating homeopathy on teenage asthma, when performed by specialists following a standardised clinical-pharmaceutical homeopathic protocol.  RBR-6XTS8Z. The Faculty of Homeopathy.

Autogenous bone versus deproteinised bovine bone matrix in 1-stage lateral sinus floor elevation in the severely atrophied maxilla: a randomised controlled trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Rotundo, Roberto; Nieri, Michele

2013-01-01

To compare 100% deproteinised bovine bone matrix (DBBM) grafts (test group) with 100% autogenous bone (AB) grafts (control group) for lateral maxillary sinus floor elevation in a parallel group, superiority, randomised controlled trial. Patients with 1 to 3 mm of residual bone height below the maxillary sinus were randomised for sinus floor elevation with DBBM and AB grafts and simultaneous implant placement. Randomisation was computer generated with allocation concealment by sealed envelopes and the radiographic examiner was blinded to group assignment. The abutment connection was performed 8 months after surgery and insertion of the provisional prostheses was performed 9 months after surgery. Outcome variables were implant failures, prosthetic failures, complications, chair time, postoperative pain and radiographic bone level 6 months after loading. Forty patients were randomised: 20 (32 implants) to the DBBM group and 20 (27 implants) to the AB group. One patient from the AB group dropped out. Two implant failures occurred in the DBBM group and no implant failure occurred in the AB group (P = 0.4872). All of the planned prostheses could be delivered. One complication occurred in the DBBM group and 2 in the AB group (P = 0.6050). Chair time was shorter for the DBBM group, with a difference of 27.3 minutes (P = 0.0428). Pain difference measured with a visual analogue scale for 6 days post-surgery was 0.2 in favour of the DBBM group (P = 0.6838). The difference in vertical bone height was 0.0 mm (95% CI -1.1, 1.1; P = 0.9703) and the difference in marginal bone level was 0.3 in favour of AB (95% CI -0.3, 0.9; P = 0.3220). No differences apart from chair time were observed when comparing DBBM and AB grafts with simultaneous implant placement in sinus elevation.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial

PubMed Central

Stewart, Ian; Beevers, Andrea; Fraser, John F; Platts, David

2017-01-01

Objective To examine whether providing thermal clothing improved the health of patients with heart failure during winter. Design Parallel group randomised controlled trial. Setting Large public hospital in Brisbane during winter 2016. Participants 91 patients with systolic or diastolic heart failure who were over 50 years old. Intervention 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients’ data were available for the primary outcome which was collected blind to randomised group. Main outcome measures The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the ‘clo’. Monitors inside the participants’ homes recorded indoor temperatures throughout winter. Results The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference –1.2 days, 95% CI –4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18°C during midwinter. Conclusions There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. Trial registration number ACTRN12615001023549; Results. PMID:28993390

Thermal clothing to reduce heart failure morbidity during winter: a randomised controlled trial.

PubMed

Barnett, Adrian Gerard; Stewart, Ian; Beevers, Andrea; Fraser, John F; Platts, David

2017-10-08

To examine whether providing thermal clothing improved the health of patients with heart failure during winter. Parallel group randomised controlled trial. Large public hospital in Brisbane during winter 2016. 91 patients with systolic or diastolic heart failure who were over 50 years old. 47 patients were randomised to receive thermal clothes (socks, top and hat) and 44 received usual care. Patients could not be blinded to their randomised group. All patients' data were available for the primary outcome which was collected blind to randomised group. The primary outcome was the mean number of days in hospital during winter. Secondary outcomes included quality of life and sleep, and blood tests were collected for cardiovascular risk factors. Participants completed clothing diaries in midwinter which were used to estimate their overall clothing insulation using the 'clo'. Monitors inside the participants' homes recorded indoor temperatures throughout winter. The mean number of days in hospital during winter was 4.2 in the usual care group and 3.0 in the thermal clothing group (mean difference -1.2 days, 95% CI -4.8 to 2.5 days). Most participants (85%) in the thermal clothing group reported using the thermals. There was an increase in overall clothing insulation at night in the thermal clothing group (mean difference 0.13 clo, 95% CI 0.03 to 0.23). Most participants in both groups did not wear sufficient clothing (defined as a clo below 1) and regularly experienced indoor temperatures below 18°C during midwinter. There was no clear statistical improvement in health in the thermal clothing group. Efforts to improve health during winter may need to focus on passive interventions such as home insulation rather than interventions that target behaviour change. ACTRN12615001023549; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study

PubMed Central

Salisbury, Lisa G; Boyd, Julia; Ramsay, Pamela; Merriweather, Judith; Huby, Guro; Forbes, John; Rattray, Janice Z; Griffith, David M; Mackenzie, Simon J; Hull, Alastair; Lewis, Steff; Murray, Gordon D

2012-01-01

Introduction Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life. Methods and analysis The authors plan a multicentre randomised parallel group complex intervention trial with concealment of group allocation from outcome assessors. Patients who required more than 48 h of mechanical ventilation and are deemed fit for intensive care unit discharge will be eligible. Patients with primary neurological diagnoses will be excluded. Participants will be randomised into one of the two groups: the intervention group will receive standard ward-based care delivered by the NHS service with additional treatment by a specifically trained generic rehabilitation assistant during ward stay and via telephone contact after hospital discharge and the control group will receive standard ward-based care delivered by the current NHS service. The intervention group will also receive additional information about their critical illness and access to a critical care physician. The total duration of the intervention will be from randomisation to 3 months postrandomisation. The total duration of follow-up will be 12 months from randomisation for both groups. The primary outcome will be the Rivermead Mobility Index at 3 months. Secondary outcomes will include measures of physical and psychological morbidity and function, quality of life and survival over a 12-month period. A health economic evaluation will also be undertaken. Groups will be compared in relation to primary and secondary outcomes; quantitative analyses will be supplemented by focus groups with patients, carers and healthcare workers. Ethics and dissemination Consent will be obtained from patients and relatives according to patient capacity. Data will be analysed according to a predefined analysis plan. Trial registration The trial is registered as ISRCTN09412438 and funded by the Chief Scientist Office, Scotland. PMID:22761291

The MATISSE study: a randomised trial of group art therapy for people with schizophrenia

PubMed Central

2010-01-01

Background Art Therapy has been promoted as a means of helping people who may find it difficult to express themselves verbally engage in psychological treatment. Group Art Therapy has been widely used as an adjunctive treatment for people with schizophrenia but there have been few attempts to examine its effects and cost effectiveness has not been examined. The MATISSE study aims to evaluate the clinical and cost effectiveness of group Art Therapy for people with schizophrenia. Method/Design The MATISSE study is a three-arm, parallel group, pragmatic, randomised, controlled trial of referral to group Art Therapy plus standard care, referral to an attention control 'activity' group plus standard care, or standard care alone. Study participants were recruited from inpatient and community-based mental health and social care services at four centres in England and Northern Ireland. Participants were aged over 18 years with a clinical diagnosis of schizophrenia, confirmed by an examination of case notes using operationalised criteria. Participants were then randomised via an independent and remote telephone randomisation service using permuted stacked blocks, stratified by site. Art Therapy and activity groups were made available to participants once a week for up to 12 months. Outcome measures were assessed by researchers masked to allocation status at 12 and 24 months after randomisation. Participants and care givers were aware which arm of the trial participants were allocated to. The primary outcomes for the study are global functioning (measured using the Global Assessment of Functioning scale) and mental health symptoms (measured using the Positive and Negative Syndrome Scale) assessed at 24 months. Secondary outcomes were assessed at 12 and 24 months and comprise levels of group attendance, social function, satisfaction with care, mental wellbeing, and costs. Discussion We believe that this is the first large scale pragmatic trial of Art Therapy for people with schizophrenia. Trial registration Current Controlled Trials ISRCTN46150447 PMID:20799930

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, Sreekumar

2015-09-09

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Desmopressin acetate (DDAVP) for preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.

PubMed

Karanth, Laxminarayan; Barua, Ankur; Kanagasabai, Sachchithanantham; Nair, N S

2013-04-30

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Home-based Reach-to-Grasp training for people after stroke is feasible: a pilot randomised controlled trial.

PubMed

Turton, A J; Cunningham, P; van Wijck, F; Smartt, Hjm; Rogers, C A; Sackley, C M; Jowett, S; Wolf, S L; Wheatley, K; van Vliet, P

2017-07-01

To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. single-blind parallel group RCT. Residual arm deficit less than 12 months post-stroke. Reach-to-Grasp training in 14 one-hour therapist's visits over 6 weeks, plus one hour self-practice per day (total 56 hours). Usual care. Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial.

Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial

PubMed Central

Heinrich, Henriette; Goetze, Oliver; Menne, Dieter; Iten, Peter X; Fruehauf, Heiko; Vavricka, Stephan R; Schwizer, Werner; Fried, Michael

2010-01-01

Objective To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms. Design Randomised controlled crossover study. Participants 20 healthy adults (14 men) aged 23-58. Interventions Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium 13Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order. Main outcome measures Cumulative percentage dose of 13C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales). Results Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of 13C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P<0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, −0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference −0.40, −0.01 to −0.79; P<0.046). No difference in dyspeptic symptoms was present. Conclusions Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms. Trial registration ClinicalTrials.gov NCT00943696. PMID:21156747

Tailored online cognitive behavioural therapy with or without therapist support calls to target psychological distress in adults receiving haemodialysis: A feasibility randomised controlled trial.

PubMed

Hudson, Joanna L; Moss-Morris, Rona; Norton, Sam; Picariello, Federica; Game, David; Carroll, Amy; Spencer, Jonathan; McCrone, Paul; Hotopf, Matthew; Yardley, Lucy; Chilcot, Joseph

2017-11-01

Psychological distress is prevalent in haemodialysis (HD) patients yet access to psychotherapy remains limited. This study assessed the feasibility and acceptability of online cognitive-behavioural therapy (CBT) tailored for HD patients, with or without therapist support, for managing psychological distress. This feasibility randomised controlled trial recruited patients from a UK HD centre. Following psychological distress screens, patients with mild-moderate psychological distress (Patient Health Questionnaire PHQ-9; score: 5-19 and/or Generalised Anxiety Disorder; GAD-7 score: 5-14) who met remaining inclusion criteria were approached for consent. Consenters were individually randomised (1:1) to online-CBT or online-CBT plus three therapist support calls. Outcomes included recruitment, retention, and adherence rates. Exploratory change analyses were performed for: psychological distress, quality of life (QoL), illness perceptions, and costs. The statistician was blinded to allocation. 182 (44%) out of 410 patients approached completed psychological distress screens. 26% found screening unacceptable; a further 30% found it unfeasible. Psychological distress was detected in 101 (55%) patients, 60 of these met remaining inclusion criteria. The primary reason for ineligibility was poor computer literacy (N=17, 53%). Twenty-five patients were randomised to the supported (N=18) or unsupported arm (N=7); 92% were retained at follow-up. No differences in psychological distress or cost-effectiveness were observed. No trial adverse events occurred. Online CBT appears feasible but only for computer literate patients who identify with the label psychological distress. A definitive trial using the current methods for psychological distress screening and online care delivery is unfeasible. ClinicalTrials.gov Identifier: NCT02352870. Copyright © 2017 Elsevier Inc. All rights reserved.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age.

PubMed

Borgatta, Lynn; Buhling, Kai J; Rybowski, Sarah; Roth, Katrin; Rosen, Kimberly

2016-10-01

To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women. Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit. Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group. LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

Effects of a probiotic intervention in acute canine gastroenteritis--a controlled clinical trial.

PubMed

Herstad, H K; Nesheim, B B; L'Abée-Lund, T; Larsen, S; Skancke, E

2010-01-01

To evaluate the effect of a probiotic product in acute self-limiting gastroenteritis in dogs. Thirty-six dogs suffering from acute diarrhoea or acute diarrhoea and vomiting were included in the study. The trial was performed as a randomised, double blind and single centre study with stratified parallel group design. The animals were allocated to equal looking probiotic or placebo treatment by block randomisation with a fixed block size of six. The probiotic cocktail consisted of thermo-stabilised Lactobacillus acidophilus and live strains of Pediococcus acidilactici, Bacillus subtilis, Bacillus licheniformis and Lactobacillus farciminis. The time from initiation of treatment to the last abnormal stools was found to be significantly shorter (P = 0.04) in the probiotic group compared to placebo group, the mean time was 1.3 days and 2.2 days, respectively. The two groups were found nearly equal with regard to time from start of treatment to the last vomiting episode. The probiotic tested may reduce the convalescence time in acute self-limiting diarrhoea in dogs.

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

PubMed

Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien Bruno; Ndour, Cheik Tidiane; Eymard-Duvernay, Sabrina; Mbouyap, Pretty Rosereine; Ayangma, Liliane; Zoungrana, Jacques; Gueye, Ndeye Fatou Ngom; Diallo, Mohamadou; Izard, Suzanne; Bado, Guillaume; Kane, Coumba Toure; Aghokeng, Avelin Fobang; Peeters, Martine; Girard, Pierre Marie; Le Moing, Vincent; Reynes, Jacques; Delaporte, Eric

2017-09-01

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (< 50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059. Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p<0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause). After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients. Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial

PubMed Central

Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

2016-01-01

Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. Trial registration numbers http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31). PMID:25425655

Intersubunit distances in full-length, dimeric, bacterial phytochrome Agp1, as measured by pulsed electron-electron double resonance (PELDOR) between different spin label positions, remain unchanged upon photoconversion.

PubMed

Kacprzak, Sylwia; Njimona, Ibrahim; Renz, Anja; Feng, Juan; Reijerse, Edward; Lubitz, Wolfgang; Krauss, Norbert; Scheerer, Patrick; Nagano, Soshichiro; Lamparter, Tilman; Weber, Stefan

2017-05-05

Bacterial phytochromes are dimeric light-regulated histidine kinases that convert red light into signaling events. Light absorption by the N-terminal photosensory core module (PCM) causes the proteins to switch between two spectrally distinct forms, Pr and Pfr, thus resulting in a conformational change that modulates the C-terminal histidine kinase region. To provide further insights into structural details of photoactivation, we investigated the full-length Agp1 bacteriophytochrome from the soil bacterium Agrobacterium fabrum using a combined spectroscopic and modeling approach. We generated seven mutants suitable for spin labeling to enable application of pulsed EPR techniques. The distances between attached spin labels were measured using pulsed electron-electron double resonance spectroscopy to probe the arrangement of the subunits within the dimer. We found very good agreement of experimental and calculated distances for the histidine-kinase region when both subunits are in a parallel orientation. However, experimental distance distributions surprisingly showed only limited agreement with either parallel- or antiparallel-arranged dimer structures when spin labels were placed into the PCM region. This observation indicates that the arrangements of the PCM subunits in the full-length protein dimer in solution differ significantly from that in the PCM crystals. The pulsed electron-electron double resonance data presented here revealed either no or only minor changes of distance distributions upon Pr-to-Pfr photoconversion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study.

PubMed

Elshof, Lotte E; Tryfonidis, Konstantinos; Slaets, Leen; van Leeuwen-Stok, A Elise; Skinner, Victoria P; Dif, Nicolas; Pijnappel, Ruud M; Bijker, Nina; Rutgers, Emiel J Th; Wesseling, Jelle

2015-08-01

The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial.

PubMed

Jairath, Vipul; Kahan, Brennan C; Gray, Alasdair; Doré, Caroline J; Mora, Ana; James, Martin W; Stanley, Adrian J; Everett, Simon M; Bailey, Adam A; Dallal, Helen; Greenaway, John; Le Jeune, Ivan; Darwent, Melanie; Church, Nicholas; Reckless, Ian; Hodge, Renate; Dyer, Claire; Meredith, Sarah; Llewelyn, Charlotte; Palmer, Kelvin R; Logan, Richard F; Travis, Simon P; Walsh, Timothy S; Murphy, Michael F

2015-07-11

Transfusion thresholds for acute upper gastrointestinal bleeding are controversial. So far, only three small, underpowered studies and one single-centre trial have been done. Findings from the single-centre trial showed reduced mortality with restrictive red blood cell (RBC) transfusion. We aimed to assess whether a multicentre, cluster randomised trial is a feasible method to substantiate or refute this finding. In this pragmatic, open-label, cluster randomised feasibility trial, done in six university hospitals in the UK, we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding, irrespective of comorbidity, except for exsanguinating haemorrhage. We randomly assigned hospitals (1:1) with a computer-generated randomisation sequence (random permuted block size of 6, without stratification or matching) to either a restrictive (transfusion when haemoglobin concentration fell below 80 g/L) or liberal (transfusion when haemoglobin concentration fell below 100 g/L) RBC transfusion policy. Neither patients nor investigators were masked to treatment allocation. Feasibility outcomes were recruitment rate, protocol adherence, haemoglobin concentration, RBC exposure, selection bias, and information to guide design and economic evaluation of the phase 3 trial. Main exploratory clinical outcomes were further bleeding and mortality at day 28. We did analyses on all enrolled patients for whom an outcome was available. This trial is registered, ISRCTN85757829 and NCT02105532. Between Sept 3, 2012, and March 1, 2013, we enrolled 936 patients across six hospitals (403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy). Recruitment rate was significantly higher for the liberal than for the restrictive policy (62% vs 55%; p=0·04). Despite some baseline imbalances, Rockall and Blatchford risk scores were identical between policies. Protocol adherence was 96% (SD 10) in the restrictive policy vs 83% (25) in the liberal policy (difference 14%; 95% CI 7-21; p=0·005). Mean last recorded haemoglobin concentration was 116 (SD 24) g/L for patients on the restrictive policy and 118 (20) g/L for those on the liberal policy (difference -2·0 [95% CI -12·0 to 7·0]; p=0·50). Fewer patients received RBCs on the restrictive policy than on the liberal policy (restrictive policy 133 [33%] vs liberal policy 247 [46%]; difference -12% [95% CI -35 to 11]; p=0·23), with fewer RBC units transfused (mean 1·2 [SD 2·1] vs 1·9 [2·8]; difference -0·7 [-1·6 to 0·3]; p=0·12), although these differences were not significant. We noted no significant difference in clinical outcomes. A cluster randomised design led to rapid recruitment, high protocol adherence, separation in degree of anaemia between groups, and non-significant reduction in RBC transfusion in the restrictive policy. A large cluster randomised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding. NHS Blood and Transplant Research and Development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Monitoring of protease catalyzed reactions by quantitative MALDI MS using metal labeling.

PubMed

Gregorius, Barbara; Jakoby, Thomas; Schaumlöffel, Dirk; Tholey, Andreas

2013-05-21

Quantitative mass spectrometry is a powerful tool for the determination of enzyme activities as it does not require labeled substrates and simultaneously allows for the identification of reaction products. However, major restrictions are the limited number of samples which can be measured in parallel due to the need for isotope labeled internal standards. Here we describe the use of metal labeling of peptides for the setup of multiplexed enzyme activity assays. After proteolytic reaction, using the protease trypsin, remaining substrates and peptide products formed in the reaction were labeled with metal chelators complexing rare earth metal ions. Labeled peptides were quantified with high accuracy and over a wide dynamic range (at least 2 orders of magnitude) using MALDI MS in case of simple peptide mixtures or by LC-MALDI MS for complex substrate mixtures and used for the monitoring of time-dependent product formation and substrate consumption. Due to multiplexing capabilities and accuracy, the presented approach will be useful for the determination of enzyme activities with a wide range of biochemical and biotechnological applications.

AExaCTT - Aerobic Exercise and Consecutive Task-specific Training for the upper limb after stroke: Protocol for a randomised controlled pilot study.

PubMed

Valkenborghs, Sarah R; Visser, Milanka M; Dunn, Ashlee; Erickson, Kirk I; Nilsson, Michael; Callister, Robin; van Vliet, Paulette

2017-09-01

Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70-85%HR max ) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke.

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01)

PubMed Central

Pagès, Pierre-Benoit; Abou Hanna, Halim; Bertaux, Anne-Claire; Serge Aho, Ludwig Serge; Magdaleinat, Pierre; Baste, Jean-Marc; Filaire, Marc; de Latour, Richard; Assouad, Jalal; Tronc, François; Jayle, Christophe; Mouroux, Jérome; Thomas, Pascal-Alexandre; Falcoz, Pierre-Emmanuel; Marty-Ané, Charles-Henri; Bernard, Alain

2017-01-01

Introduction In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. Methods and analysis The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. Ethics and dissemination The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. Trial registration number NCT02502318. PMID:28619764

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

PubMed

Lo, Jessica W; Bunce, Catey; Charteris, David; Banerjee, Philip; Phillips, Rachel; Cornelius, Victoria R

2016-08-02

Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery

PubMed Central

Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-01-01

Introduction Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions—physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. Methods and analysis This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. Ethics and dissemination This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. Trial registration number NCT02921932 (ClinicalTrials.gov) PMID:28778994

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

PubMed Central

2012-01-01

Background To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation. Methods An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews. Results The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises. Conclusions It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability. Trial registration UKCRN 7090; ISRCTN: 80875696 PMID:22676069

Neurofeedback ineffective in paediatric brain tumour survivors: Results of a double-blind randomised placebo-controlled trial.

PubMed

de Ruiter, Marieke Anna; Oosterlaan, Jaap; Schouten-van Meeteren, Antoinette Yvonne Narda; Maurice-Stam, Heleen; van Vuurden, Dannis Gilbert; Gidding, Corrie; Beek, Laura Rachel; Granzen, Bernd; Caron, Huib N; Grootenhuis, Martha Alexandra

2016-09-01

Many paediatric brain tumour survivors (PBTS) suffer from neurocognitive impairments. Promising effects of neurofeedback (NF) on neurocognitive functioning have been reported, however research into NF for PBTS has not been conducted. We investigated the effects of NF on neurocognitive functioning in PBTS using a double-blind randomised placebo-controlled trial with a parallel-group design (Pediatric Research on Improving Speed, Memory, and Attention; the PRISMA study). Eligible for inclusion were PBTS with neurocognitive complaints, aged 8-18 years, >2 years post-treatment. They were recruited from five medical centres in the Netherlands. A randomisation table assigned participants to 30 sessions (two per week) of either NF or placebo feedback (PF) (ratio 1:1). Participants, parents, trainers, and researchers handling the data were blinded to group assignment. Participants were assessed pre-, post- and 6 months post-training to determine whether NF training would lead to improved functioning as compared with PF training. Primary outcome measures were attention, processing speed, memory, executive functioning, visuomotor integration, and intelligence. Linear mixed models analyses were used to test differences between NF and PF training over time. A total of 82 children were enrolled (mean age 13.9 years, standard deviation = 3.2, 49% males); 80 participants were randomised (NF: n = 40, PF n = 40); 71 participants completed the training (NF: n = 34, PF: n = 37); 68 participants completed training and 6 months post-training assessment (NF: n = 33, PF: n = 35). Similar improvements were found over time for the two treatment groups on the primary outcomes (all p's > 0.15). Results indicated no specific treatment-effects of NF on neurocognitive functioning of PBTS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Guided Internet-based versus face-to-face clinical care in the management of tinnitus: study protocol for a multi-centre randomised controlled trial.

PubMed

Beukes, Eldré W; Baguley, David M; Allen, Peter M; Manchaiah, Vinaya; Andersson, Gerhard

2017-04-21

Innovative strategies are required to improve access to evidence-based tinnitus interventions. A guided Internet-based cognitive behavioural therapy (iCBT) intervention for tinnitus was therefore developed for a U.K. Initial clinical trials indicated efficacy of iCBT at reducing tinnitus severity and associated comorbidities such as insomnia and depression. The aim of this phase III randomised controlled trial is to compare this new iCBT intervention with an established intervention, namely face-to-face clinical care for tinnitus. This will be a multi-centre study undertaken across three hospitals in the East of England. The design is a randomised, two-arm, parallel-group, non-inferiority trial with a 2-month follow-up. The experimental group will receive the guided iCBT intervention, whereas the active control group will receive the usual face-to-face clinical care. An independent researcher will randomly assign participants, using a computer-generated randomisation schedule, after stratification for tinnitus severity. There will be 46 participants in each group. The primary assessment measure will be the Tinnitus Functional Index. Data analysis will establish whether non-inferiority is achieved using a pre-defined non-inferiority margin. This protocol outlines phase III of a clinical trial comparing a new iCBT with established face-to-face care for tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual tinnitus care, it may be a viable additional management route for individuals with tinnitus. This could increase access to evidence-based effective tinnitus care and reduce the pressures on existing health care systems. ClinicalTrials.gov identifier: NCT02665975 . Registered on 22 January 2016.

Impact of a Brief Group Intervention to Enhance Parenting and the Home Learning Environment for Children Aged 6-36 Months: a Cluster Randomised Controlled Trial.

PubMed

Hackworth, N J; Berthelsen, D; Matthews, J; Westrupp, E M; Cann, W; Ukoumunne, O C; Bennetts, S K; Phan, T; Scicluna, A; Trajanovska, M; Yu, M; Nicholson, J M

2017-04-01

This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6-12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12-36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and 'standard'/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. 8 September 2011; ACTRN12611000965909 .

Effect of a 16-week Bikram yoga program on perceived stress, self-efficacy and health-related quality of life in stressed and sedentary adults: A randomised controlled trial.

PubMed

Hewett, Zoe L; Pumpa, Kate L; Smith, Caroline A; Fahey, Paul P; Cheema, Birinder S

2018-04-01

The purpose of this study was to investigate the effect of 16 weeks of Bikram yoga on perceived stress, self-efficacy and health related quality of life (HRQoL) in sedentary, stressed adults. 16 week, parallel-arm, randomised controlled trial with flexible dosing. Physically inactive, stressed adults (37.2±10.8 years) were randomised to Bikram yoga (three to five classes per week) or control (no treatment) group for 16 weeks. Outcome measures, collected via self-report, included perceived stress, general self-efficacy, and HRQoL. Outcomes were assessed at baseline, midpoint and completion. Individuals were randomised to the experimental (n=29) or control group (n=34). Average attendance in the experimental group was 27±18 classes. Repeated measure analyses of variance (intention-to-treat) demonstrated significantly improved perceived stress (p=0.003, partial η 2 =0.109), general self-efficacy (p=0.034, partial η 2 =0.056), and the general health (p=0.034, partial η 2 =0.058) and energy/fatigue (p=0.019, partial η 2 =0.066) domains of HRQoL in the experimental group versus the control group. Attendance was significantly associated with reductions in perceived stress, and an increase in several domains of HRQoL. 16 weeks of Bikram yoga significantly improved perceived stress, general self-efficacy and HRQoL in sedentary, stressed adults. Future research should consider ways to optimise adherence, and should investigate effects of Bikram yoga intervention in other populations at risk for stress-related illness. Australia New Zealand Clinical Trials Registry ACTRN12616000867493. Registered 04 July 2016. URL: http://www.anzctr.org.au/ACTRN12616000867493.aspx. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

SABRE: a multicentre randomised control trial of nebulised hypertonic saline in infants hospitalised with acute bronchiolitis.

PubMed

Everard, Mark L; Hind, Daniel; Ugonna, Kelechi; Freeman, Jennifer; Bradburn, Mike; Cooper, Cindy L; Cross, Elizabeth; Maguire, Chin; Cantrill, Hannah; Alexander, John; McNamara, Paul S

2014-12-01

Acute bronchiolitis is the commonest cause for hospitalisation in infancy. Supportive care remains the cornerstone of current management and no other therapy has been shown to influence the course of the disease. It has been suggested that adding nebulised hypertonic saline to usual care may shorten the duration of hospitalisation. To determine whether hypertonic saline does have beneficial effects we undertook an open, multi-centre parallel-group, pragmatic RCT in ten UK hospitals. Infants admitted to hospital with a clinical diagnosis of acute bronchiolitis and requiring oxygen therapy were randomised to receive usual care alone or nebulised 3% hypertonic saline (HS) administered 6-hourly. Randomisation was within 4 h of admission. The primary outcome was time to being assessed as 'fit' for discharge with secondary outcomes including time to discharge, incidence of adverse events together with follow up to 28 days assessing patient centred health related outcomes. A total of 317 infants were recruited to the study. 158 infants were randomised to HS (141 analysed) and 159 to standard care (149 analysed). There was no difference between the two arms in time to being declared fit for discharge (hazard ratio: 0-95, 95% CI: 0.75-1.20) nor to actual discharge (hazard ratio: 0.97, 95% CI: 0.76-1.23). There was no difference in adverse events. One infant in the HS group developed bradycardia with desaturation. This study does not support the use of nebulised HS in the treatment of acute bronchiolitis over usual care with minimal handlings. NCT01469845. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough.

PubMed

Marchant, Julie; Masters, Ian Brent; Champion, Anita; Petsky, Helen; Chang, Anne B

2012-08-01

Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. 50 children (median age 1.9 years, IQR 0.9-5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was 'cough resolution' defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0-2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15-2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children. ACTRN 12605000533695.

Self-managed loaded exercise versus usual physiotherapy treatment for rotator cuff tendinopathy: a pilot randomised controlled trial.

PubMed

Littlewood, Chris; Malliaras, Peter; Mawson, Sue; May, Stephen; Walters, Stephen J

2014-03-01

Rotator cuff tendinopathy is a common source of shoulder pain characterised by persistent and/or recurrent problems for a proportion of sufferers. The aim of this study was to pilot the methods proposed to conduct a substantive study to evaluate the effectiveness of a self-managed loaded exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. A single-centre pragmatic unblinded parallel group pilot randomised controlled trial. One private physiotherapy clinic, northern England. Twenty-four participants with rotator cuff tendinopathy. The intervention was a programme of self-managed loaded exercise. The control group received usual physiotherapy treatment. Baseline assessment comprised the Shoulder Pain and Disability Index (SPADI) and the Short-Form 36, repeated three months post randomisation. The recruitment target was met and the majority of participants (98%) were willing to be randomised. 100% retention was attained with all participants completing the SPADI at three months. Exercise adherence rates were excellent (90%). The mean change in SPADI score was -23.7 (95% CI -14.4 to -33.3) points for the self-managed exercise group and -19.0 (95% CI -6.0 to -31.9) points for the usual physiotherapy treatment group. The difference in three month SPADI scores was 0.1 (95% CI -16.6 to 16.9) points in favour of the usual physiotherapy treatment group. In keeping with previous research which indicates the need for further evaluation of self-managed loaded exercise for rotator cuff tendinopathy, these methods and the preliminary evaluation of outcome offer a foundation and stimulus to conduct a substantive study. Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial.

PubMed

Zhang, Qin-hong; Yue, Jin-huan; Li, Chao-ran; Sun, Zhong-ren

2014-12-30

Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers. This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation. This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers. ChiCTR-TRC-13003959. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PREvention STudy On preventing or reducing disability from musculoskeletal complaints in music school students (PRESTO): protocol of a randomised controlled trial.

PubMed

Baadjou, Vera A E; Verbunt, Jeanine A M C F; Eijsden-Besseling, Marjon D F van; Samama-Polak, Ans L W; Bie, Rob A D E; Smeets, Rob J E M

2014-12-01

Up to 87% of professional musicians develop work-related complaints of the musculoskeletal system during their careers. Music school students are at specific risk for developing musculoskeletal complaints and disabilities. This study aims to evaluate the effectiveness of a biopsychosocial prevention program to prevent or reduce disabilities from playing-related musculoskeletal disorders. Secondary objectives are evaluation of cost-effectiveness and feasibility. Healthy, first or second year students (n=150) will be asked to participate in a multicentre, single-blinded, parallel-group randomised controlled trial. Students randomised to the intervention group (n=75) will participate in a biopsychosocial prevention program that addresses playing-related health problems and provides postural training according to the Mensendieck or Cesar methods of postural exercise therapy, while incorporating aspects from behavioural change theories. A control group (n=75) will participate in a program that stimulates a healthy physical activity level using a pedometer, which conforms to international recommendations. No long-term effects are expected from this control intervention. Total follow-up duration is two years. The primary outcome measure is disability (Disabilities of Arm, Shoulder and Hand questionnaire). The secondary outcome measures are pain, quality of life and changes in health behaviour. Multilevel mixed-effect logistic or linear regression analyses will be performed to analyse the effects of the program on the aforementioned outcome measurements. Furthermore, cost-effectiveness, cost-utility and feasibility will be analysed. It is believed that this is the first comprehensive randomised controlled trial on the effect and rationale of a biopsychosocial prevention program for music students. Copyright © 2014 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment

PubMed Central

Davidson, Giana H; Flum, David R; Talan, David A; Kessler, Larry G; Lavallee, Danielle C; Bizzell, Bonnie J; Farjah, Farhood; Stewart, Skye D; Krishnadasan, Anusha; Carney, Erin E; Wolff, Erika M; Comstock, Bryan A; Monsell, Sarah E; Heagerty, Patrick J; Ehlers, Annie P; DeUgarte, Daniel A; Kaji, Amy H; Evans, Heather L; Yu, Julianna T; Mandell, Katherine A; Doten, Ian C; Clive, Kevin S; McGrane, Karen M; Tudor, Brandon C; Foster, Careen S; Saltzman, Darin J; Thirlby, Richard C; Lange, Erin O; Sabbatini, Amber K; Moran, Gregory J

2017-01-01

Introduction Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%–15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy. Objectives The Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy. Methods/Analysis CODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4 weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm. Ethics and dissemination This trial was approved by the University of Washington’s Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals. Trial registration number NCT02800785. PMID:29146633

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

PubMed Central

Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

2015-01-01

Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery.

PubMed

Abdullah, Hairil Rizal; Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-08-04

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. NCT02921932 (ClinicalTrials.gov). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).

PubMed

Lam, Ching; Tan, Wei; Leighton, Matthew; Hastings, Margaret; Lingaya, Melanie; Falcone, Yirga; Zhou, Xiaoying; Xu, Luting; Whorwell, Peter; Walls, Andrew F; Zaitoun, Abed; Montgomery, Alan; Spiller, Robin

2016-01-01

Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. NCT01316718. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial).

PubMed

Grant, A M; Boachie, C; Cotton, S C; Faria, R; Bojke, L; Epstein, D M; Ramsay, C R; Corbacho, B; Sculpher, M; Krukowski, Z H; Heading, R C; Campbell, M K

2013-06-01

Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. Current Controlled Trials ISRCTN15517081. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.

Group-based antenatal birth and parent preparation for improving birth outcomes and parenting resources: study protocol for a randomised trial.

PubMed

Koushede, Vibeke; Brixval, Carina Sjöberg; Axelsen, Solveig Forberg; Lindschou, Jane; Winkel, Per; Maimburg, Rikke Damkjær; Due, Pernille

2013-10-01

To examine the efficacy and cost-effectiveness of group based antenatal education for improving childbirth and parenting resources compared to auditorium based education. 2350 Danish pregnant women and their partners ≥18 years old, recruited before 20+0 gestational weeks. Population-based individually randomised superiority trial with two parallel arms: Four sessions of birth and parent preparation in small groups (experimental group); two lectures in an auditorium (control group). Data is collected by (1) questionnaires at baseline (≈18 weeks of gestation), 37 weeks of gestation, 9 weeks-, 6 months-, and 1 year post-partum, (2) the hospital obstetric database, (3) national registers. use of epidural analgesia. stress, parenting alliance; explorative outcomes: depressive symptoms, use of health care services, self-efficacy, well-being, family break-ups. Analyses will be intention-to-treat as well as per protocol. Process evaluation will be conducted using questionnaires and qualitative interviews. The incremental societal cost of the intervention will be computed and compared to the measured outcomes in a cost-effectiveness analysis. To the best of our knowledge this is the largest well-designed randomised trial of its kind to date. The trial will bring much-needed evidence for decision makers of the content and form of antenatal education. Copyright © 2013 Elsevier B.V. All rights reserved.

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

PubMed

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Disc extrusions and bulges in nonspecific low back pain and sciatica: Exploratory randomised controlled trial comparing yoga therapy and normal medical treatment.

PubMed

Monro, Robin; Bhardwaj, Abhishek Kumar; Gupta, Ram Kumar; Telles, Shirley; Allen, Beth; Little, Paul

2015-01-01

Previous trials of yoga therapy for nonspecific low back pain (nsLBP) (without sciatica) showed beneficial effects. To test effects of yoga therapy on pain and disability associated with lumbar disc extrusions and bulges. Parallel-group, randomised, controlled trial. Sixty-one adults from rural population, aged 20-45, with nsLBP or sciatica, and disc extrusions or bulges. Randomised to yoga (n=30) and control (n=31). Yoga: 3-month yoga course of group classes and home practice, designed to ensure safety for disc extrusions. normal medical care. OUTCOME MEASURES (3-4 months) Primary: Roland Morris Disability Questionnaire (RMDQ); worst pain in past two weeks. Secondary: Aberdeen Low Back Pain Scale; straight leg raise test; structural changes. Disc projections per case ranged from one bulge or one extrusion to three bulges plus two extrusions. Sixty-two percent had sciatica. Intention-to-treat analysis of the RMDQ data, adjusted for age, sex and baseline RMDQ scores, gave a Yoga Group score 3.29 points lower than Control Group (0.98, 5.61; p=0.006) at 3 months. No other significant differences in the endpoints occurred. No adverse effects of yoga were reported. Yoga therapy can be safe and beneficial for patients with nsLBP or sciatica, accompanied by disc extrusions and bulges.

Efficacy of Chlorhexidine, Xylitol, and Chlorhexidine + Xylitol against Dental Plaque, Gingivitis, and Salivary Streptococcus mutans Load: A Randomised Controlled Trial.

PubMed

Marya, Charu Mohan; Taneja, Pratibha; Nagpal, Ruchi; Marya, Vandana; Oberoi, Sukhvinder Singh; Arora, Dimple

To compare the antiplaque, antigingivitis and antibacterial efficacy of chlorhexidine (CHX), XYL and a mouthwash combining CHX and XYL against Streptococcus mutans (S. mutans). A parallel design, randomised controlled trial was conducted among 75 dental students. Participants were randomised into CHX, CHX+XYL and XYL-only groups using the lottery method. Subjects were instructed to use 10 ml of the provided mouthwash for 15 s twice daily for 3 weeks. All the outcome measures, gingival index (GI), plaque index (PI) and number of salivary S. mutans CFU were recorded at baseline and 3 weeks post intervention. Nonparametric tests were used for inferential statistics. All outcome variables (GI, PI scores and log10 salivary S. mutans counts) decreased significantly from baseline compared to post intervention among all three groups. Intergroup comparison demonstrated that reduction in GI was not significantly different among the three groups. The decrease in PI scores was found to be significantly higher in the XYL group, while the decrease in the log10 salivary S. mutans count was significantly higher in the CHX+XYL group. The present study provided sufficient data to suggest that all the three mouthwashes are effective against plaque, gingivitis and S. mutans load in saliva. Further investigations should be carried out to confirm the results and develop strategies for using such products to prevent tooth decay.

Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (PARAMEDIC-2): Trial protocol.

PubMed

Perkins, Gavin D; Quinn, Tom; Deakin, Charles D; Nolan, Jerry P; Lall, Ranjit; Slowther, Anne-Marie; Cooke, Matthew; Lamb, Sarah E; Petrou, Stavros; Achana, Felix; Finn, Judith; Jacobs, Ian G; Carson, Andrew; Smyth, Mike; Han, Kyee; Byers, Sonia; Rees, Nigel; Whitfield, Richard; Moore, Fionna; Fothergill, Rachael; Stallard, Nigel; Long, John; Hennings, Susie; Horton, Jessica; Kaye, Charlotte; Gates, Simon

2016-11-01

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest. This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant. 8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes). Trial registration (ISRCTN73485024). Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Study protocol: can a school gardening intervention improve children’s diets?

PubMed Central

2012-01-01

Background The current academic literature suggests there is a potential for using gardening as a tool to improve children’s fruit and vegetable intake. This study is two parallel randomised controlled trials (RCT) devised to evaluate the school gardening programme of the Royal Horticultural Society (RHS) Campaign for School Gardening, to determine if it has an effect on children’s fruit and vegetable intake. Method/Design Trial One will consist of 26 schools; these schools will be randomised into two groups, one to receive the intensive intervention as “Partner Schools” and the other to receive the less intensive intervention as “Associate Schools”. Trial Two will consist of 32 schools; these schools will be randomised into either the less intensive intervention “Associate Schools” or a comparison group with delayed intervention. Baseline data collection will be collected using a 24-hour food diary (CADET) to collect data on dietary intake and a questionnaire exploring children’s knowledge and attitudes towards fruit and vegetables. A process measures questionnaire will be used to assess each school’s gardening activities. Discussion The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children’s fruit and vegetable intake. The evaluation will provide valuable information for designing future research in primary school children’s diets and school based interventions. Trial registration ISRCTN11396528 PMID:22537179

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention

PubMed Central

Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John

2016-01-01

Introduction Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. Methods and analysis 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethics and dissemination Ethical approval has been obtained from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. Trial registration number ChiCTR-IOR-15006971. PMID:27334883

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren’s Syndrome

PubMed Central

2014-01-01

Background Primary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration UKCRN Portfolio ID: 9809 ISRCTN65360827. PMID:24438039

Unsupervised chunking based on graph propagation from bilingual corpus.

PubMed

Zhu, Ling; Wong, Derek F; Chao, Lidia S

2014-01-01

This paper presents a novel approach for unsupervised shallow parsing model trained on the unannotated Chinese text of parallel Chinese-English corpus. In this approach, no information of the Chinese side is applied. The exploitation of graph-based label propagation for bilingual knowledge transfer, along with an application of using the projected labels as features in unsupervised model, contributes to a better performance. The experimental comparisons with the state-of-the-art algorithms show that the proposed approach is able to achieve impressive higher accuracy in terms of F-score.

Unlabeled multi tumor marker detection system based on bioinitiated light addressable potentiometric sensor.

PubMed

Jia, Yun-Fang; Gao, Chun-Ying; He, Jia; Feng, Dao-Fu; Xing, Ke-Li; Wu, Ming; Liu, Yang; Cai, Wen-Sheng; Feng, Xi-Zeng

2012-08-21

Multi biomarkers' assays are of great significance in clinical diagnosis. A label-free multi tumor markers' parallel detection system was proposed based on a light addressable potentiometric sensor (LAPS). Arrayed LAPS chips with basic structure of Si(3)N(4)-SiO(2)-Si were prepared on silicon wafers, and the label-free parallel detection system for this component was developed with user friendly controlling interfaces. Then the l-3,4-dihydroxyphenyl-alanine (L-Dopa) hydrochloric solution was used to initiate the surface of LAPS. The L-Dopa immobilization state was investigated by the theoretical calculation. L-Dopa initiated LAPS' chip was biofunctionalized respectively by the antigens and antibodies of four tumor markers, α-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and Ferritin. Then unlabeled antibodies and antigens of these four biomarkers were detected by the proposed detection systems. Furthermore physical and measuring principles in this system were described, and qualitative understanding for experimental data were given. The measured response ranges were compared with their clinical cutoff values, and sensitivities were calculated by OriginLab. The results indicate that this bioinitiated LAPS based label-free detection system may offer a new choice for the realization of unlabeled multi tumor markers' clinical assay.

Determination of freeze damage on HPV vaccines by use of flow cytometry.

PubMed

Østergaard, Erik; Frandsen, Peer Lyng; Sandberg, Eva

2015-07-01

The human papillomavirus (HPV) vaccines Gardasil, Silgard and Cervarix were labeled with antibodies against HPV strain 6 or 16/FITC conjugated secondary antibodies and analyzed by flow cytometry. The vaccines showed distinct peaks of fluorescent particles, and a shift towards decreased fluorescent particles was observed after incubation of the vaccines over night at -20 °C. Since parallel distributed vaccines could have longer route of transportation there is an increased risk of freeze damage for these types of vaccine. Shift in fluorescence of labeled vaccine particles was used to indicate whether parallel distributed Silgard, which is a vaccine type identical to Gardasil, was exposed to freeze damage during transportation, but no shift was observed. Additional experiments showed that the HPV vaccines could be degraded to smaller particles by citric acid/phosphate buffer treatment. The majority of particles detected in degraded Gardasil were very small indicating that the particles are HPV virus like particle (VLPs) labeled with antibodies, but Cervarix could only be degraded partially due to the presence of another type adjuvant in this vaccine. The described method may be useful in characterization of adjuvanted vaccines with respect to freeze damage, and to characterize vaccines containing particles corresponding to VLPs in size. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials.

PubMed

Gane, Edward J; Pianko, Stephen; Roberts, Stuart K; Thompson, Alexander J; Zeuzem, Stefan; Zuckerman, Eli; Ben-Ari, Ziv; Foster, Graham R; Agarwal, Kosh; Laursen, Alex L; Gerstoft, Jan; Gao, Wei; Huang, Hsueh-Cheng; Fitzgerald, Brian; Fernsler, Doreen; Li, Jerry J; Grandhi, Anjana; Liu, Hong; Su, Feng-Hsiu; Wan, Shuyan; Zeng, Zhen; Chen, Huei-Ling; Dutko, Frank J; Nguyen, Bach-Yen T; Wahl, Janice; Robertson, Michael N; Barr, Eliav; Yeh, Wendy W; Plank, Rebeca M; Butterton, Joan R; Esteban, Rafael

2017-11-01

New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibitor, either elbasvir (50 mg once daily) or ruzasvir (MK-8408; 60 mg once daily), and to evaluate the safety and tolerability of these combination regimens in individuals infected with genotypes 1, 2, or 3. Part A of these phase 2, randomised, multicentre, open-label, clinical trials enrolled participants from 11 countries, aged 18 years or older, chronically infected with HCV genotypes 1, 2, or 3, with HCV RNA of at least 10 000 IU/mL, without evidence of cirrhosis, who had not received previous treatment for HCV infection. Within each HCV genotype, participants were randomly assigned (1:1:1:1) with a block size of 4, to open-label treatment to one of four treatment groups: grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (300 mg/day); grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (450 mg/day); grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (300 mg/day); or grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (450 mg/day), according to a computer-generated allocation schedule. Randomisation was centrally implemented using an interactive voice response system and integrated web response system. The primary endpoint was the proportion of participants achieving sustained virological response at 12 weeks (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the end of all study therapy) in the per-protocol analysis set, which included all participants who were randomised and received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT02332707 and NCT02332720. 241 participants were randomised between Feb 18, 2015, and March 16, 2015. 240 participants completed 8 weeks of treatment and reached follow-up 12 weeks after the end of treatment. Of the four regimens, grazoprevir plus ruzasvir plus uprifosbuvir 450 mg had the most consistently high SVR12 (>90%) for participants infected with genotype 1 (21 [91%] of 23), genotype 2 (15 [94%] of 16), and genotype 3 (20 [91%] of 22). In particular, among those with genotype 2 infection, the grazoprevir plus ruzasvir plus uprifosbuvir 450 mg regimen had a higher SVR12 (15 [94%] of 16) than the grazoprevir plus ruzasvir plus uprifosbuvir 300 mg regimen (ten [71%] of 14), grazoprevir plus elbasvir plus uprifosbuvir 300 mg regimen (11 [69%] of 16), or grazoprevir plus elbasvir plus uprifosbuvir 450 mg regimen (nine [60%] of 15). Overall, the most common adverse events were headache (55 [23%] of 240), fatigue (47 [20%] of 240), and nausea (32 [13%] of 240). Two (<1%) of 240 participants had serious adverse events (pharyngeal abscess and keratitis), which were not considered drug related by the respective investigators. These results support further evaluation of the three-drug direct-acting antiviral agent regimen of grazoprevir 100 mg plus ruzasvir 60 mg plus uprifosbuvir 450 mg among a more diverse HCV-infected population, including those with compensated cirrhosis, previous treatment with an interferon-containing regimen, and HCV-HIV co-infection. Merck & Co, Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effectiveness and safety of combining varenicline with nicotine e-cigarettes for smoking cessation in people with mental illnesses and addictions: study protocol for a randomised-controlled trial.

PubMed

Bullen, Chris; Verbiest, Marjolein; Galea-Singer, Susanna; Kurdziel, Tomasz; Laking, George; Newcombe, David; Parag, Varsha; Walker, Natalie

2018-05-04

Smoking rates are higher in New Zealand (NZ) adults with mental illnesses and alcohol and other drug (AOD) addictions, compared to the overall population. Quit attempts using "gold standard" smoking cessation treatments often fail in people with these conditions, so more flexible treatment regimens that adapt to a person's responsiveness to treatment are worth investigating. The STATUS trial aims to evaluate the effectiveness and safety of combining varenicline with nicotine e-cigarettes for smoking cessation among varenicline non-responders in treatment for mental health illnesses and/or AOD addictions. This is a pragmatic two-arm, open-label, randomised trial. Participants will be daily smokers using mental health and/or addiction services in Auckland, aged ≥18 years, motivated to quit smoking, and eligible to access varenicline through the NZ special authority process. After 2 weeks of using varenicline plus behavioural support, participants who have not reduced their daily smoking by ≥50% will be randomised (1:1) to either 10 weeks of continued varenicline use or 10 weeks of varenicline plus an 18 mg/mL nicotine e-cigarette. All participants will receive weekly withdrawal-orientated behavioural support calls for 6 weeks post-randomisation. The primary outcome is self-reported biochemically-verified (exhaled carbon monoxide) continuous abstinence at 24 weeks post-randomisation. Secondary outcomes, measured at six, 12 and 24 weeks post-randomisation include: self-reported continuous abstinence, 7-day point prevalence abstinence, smoking reduction, time to relapse, cross-over, use of other smoking cessation support, serious adverse events, treatment adherence, compliance, acceptability, dual use, continuation of treatment use, mental illness symptoms and AOD use, health-related quality of life, and cost-analysis. A sample size of 338 will confer 80% power (p = 0.05) to detect a 15% absolute difference between the varenicline alone and varenicline plus e-cigarette groups. People with mental illness and/or AOD addictions are just as motivated as others to quit smoking, but are less likely to succeed. Adapting smoking cessation medication after a lack of responsiveness in the first 2 weeks of initial treatment in this priority population by adding a nicotine e-cigarette may be one way to increase long-term quit rates. Australian NZ Clinical Trial Registry: ACTRN12616001355460 (29 September 2016).

Metrics for Labeled Markov Systems

NASA Technical Reports Server (NTRS)

Desharnais, Josee; Jagadeesan, Radha; Gupta, Vineet; Panangaden, Prakash

1999-01-01

Partial Labeled Markov Chains are simultaneously generalizations of process algebra and of traditional Markov chains. They provide a foundation for interacting discrete probabilistic systems, the interaction being synchronization on labels as in process algebra. Existing notions of process equivalence are too sensitive to the exact probabilities of various transitions. This paper addresses contextual reasoning principles for reasoning about more robust notions of "approximate" equivalence between concurrent interacting probabilistic systems. The present results indicate that:We develop a family of metrics between partial labeled Markov chains to formalize the notion of distance between processes. We show that processes at distance zero are bisimilar. We describe a decision procedure to compute the distance between two processes. We show that reasoning about approximate equivalence can be done compositionally by showing that process combinators do not increase distance. We introduce an asymptotic metric to capture asymptotic properties of Markov chains; and show that parallel composition does not increase asymptotic distance.

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

PubMed

Henao-Restrepo, Ana Maria; Camacho, Anton; Longini, Ira M; Watson, Conall H; Edmunds, W John; Egger, Matthias; Carroll, Miles W; Dean, Natalie E; Diatta, Ibrahima; Doumbia, Moussa; Draguez, Bertrand; Duraffour, Sophie; Enwere, Godwin; Grais, Rebecca; Gunther, Stephan; Gsell, Pierre-Stéphane; Hossmann, Stefanie; Watle, Sara Viksmoen; Kondé, Mandy Kader; Kéïta, Sakoba; Kone, Souleymane; Kuisma, Eewa; Levine, Myron M; Mandal, Sema; Mauget, Thomas; Norheim, Gunnstein; Riveros, Ximena; Soumah, Aboubacar; Trelle, Sven; Vicari, Andrea S; Røttingen, John-Arne; Kieny, Marie-Paule

2017-02-04

rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×10 7 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9-100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3-100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae. The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters. WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development). Copyright © 2017 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

PubMed Central

Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

2013-01-01

Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial

PubMed Central

Naumann, M; Lowe, N J

2001-01-01

Objectives To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. Design Multicentre, randomised, parallel group, placebo controlled trial. Setting 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. Participants Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. Interventions Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhidrotic area of each axilla, defined by Minor's iodine starch test. Main outcome measures Percentage of responders (patients with ⩾50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. Results At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). Conclusion Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction. What is already known on this topicPrimary hyperhidrosis is a chronic disorder that can affect any part of the body, especially the axillas, palms, feet, and faceCurrent treatments are often ineffective, short acting, or poorly toleratedWhat this study addsBotulinum toxin type A was significantly better than placebo on all measures of sweatingPatient satisfaction was high and few adverse events were reportedEffects of treatment remained apparent at 16 weeks PMID:11557704

A parallel-group, randomised controlled trial of a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners: design and rationale

PubMed Central

Lambert, Sylvie D; Girgis, Afaf; McElduff, Patrick; Turner, Jane; Levesque, Janelle V; Kayser, Karen; Mihalopoulos, Cathrine; Shih, Sophy T F; Barker, Daniel

2013-01-01

Introduction Coping skills training interventions have been found to be efficacious in helping both patients and their partners manage the physical and emotional challenges they face following a cancer diagnosis. However, many of these interventions are costly and not sustainable. To overcome these issues, a self-directed format is increasingly used. The efficacy of self-directed interventions for patients has been supported; however, no study has reported on the outcomes for their partners. This study will test the efficacy of Coping-Together—a multimedia, self-directed, coping skills training intervention for patients with cancer and their partners. Methods and analysis The proposed three-group, parallel, randomised controlled trial will recruit patients diagnosed in the past 4 months with breast, prostate, colorectal cancer or melanoma through their treating clinician. Patients and their partners will be randomised to (1) a minimal ethical care (MEC) condition—selected Cancer Council New South Wales booklets and a brochure for the Cancer Council Helpline, (2) Coping-Together generic—MEC materials, the six Coping-Together booklets and DVD, the Cancer Council Queensland relaxation audio CD and login to the Coping-Together website or (3) Coping-Together tailored—MEC materials, the Coping-Together DVD, the login to the website and only those Coping-Together booklet sections that pertain to their direct concerns. Anxiety (primary outcome), distress, depression, dyadic adjustment, quality of life, illness or caregiving appraisal, self-efficacy and dyadic and individual coping will be assessed before receiving the study material (ie, baseline) and again at 3, 6 and 12 months postbaseline. Intention-to-treat and per protocol analysis will be conducted. Ethics and dissemination This study has been approved by the relevant local area health and University ethics committees. Study findings will be disseminated not only through peer-reviewed publications and conference presentations but also through educational outreach visits, publication of lay research summaries in consumer newsletters and publications targeting clinicians. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613000491763 (03/05/2013) PMID:23883890

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

PubMed Central

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-01-01

Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259

Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN).

PubMed

Griffin, D R; Dickenson, E J; Wall, P D H; Donovan, J L; Foster, N E; Hutchinson, C E; Parsons, N; Petrou, S; Realpe, A; Achten, J; Achana, F; Adams, A; Costa, M L; Griffin, J; Hobson, R; Smith, J

2016-08-31

Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. ISRCTN64081839; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Efficacy and safety of monotherapy with sirukumab compared with adalimumab monotherapy in biologic-naïve patients with active rheumatoid arthritis (SIRROUND-H): a randomised, double-blind, parallel-group, multinational, 52-week, phase 3 study.

PubMed

Taylor, Peter C; Schiff, Michael H; Wang, Qingmin; Jiang, Yusang; Zhuang, Yanli; Kurrasch, Regina; Daga, Shruti; Rao, Ravi; Tak, Paul P; Hsu, Benjamin

2018-05-01

This randomised, double-blind, parallel-group, phase 3 study compared monotherapy with sirukumab, an anti-interleukin-6 cytokine monoclonal antibody, with adalimumab monotherapy in patients with rheumatoid arthritis (RA). Biologic-naïve patients with active RA who were inadequate responders or were intolerant to, or inappropriate for, methotrexate were randomised to subcutaneous sirukumab 100 mg every 2 weeks (n=187), sirukumab 50 mg every 4 weeks (n=186) or adalimumab 40 mg every 2 weeks (n=186). Primary endpoints at week 24 were change from baseline in Disease Activity Score in 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) and proportion of patients achieving an American College of Rheumatology (ACR) 50 response; these endpoints were tested in sequential order. This study is registered at EudraCT (number: 2013-001417-32) and ClinicalTrials.gov (number: NCT02019472). Significantly greater improvements from baseline in mean (SD) DAS28 (ESR) were observed at week 24 with sirukumab 100 mg every 2 weeks (-2.96 (1.580)) versus adalimumab 40 mg every 2 weeks (-2.19 (1.437); P<0.001). Sirukumab 50 mg every 4 weeks also showed significantly greater improvement from baseline at week 24 in DAS28 (ESR) (-2.58 (1.524)) compared with adalimumab (P=0.013). The ACR50 response rates with the 100 mg (35.3%) and 50 mg (26.9%) doses of sirukumab were comparable to that with adalimumab (31.7%) at week 24. The safety profile of sirukumab was consistent with that observed with anti-interleukin-6 receptor antibodies. A dose-related effect on the incidence of injection-site reactions was observed with sirukumab. Sirukumab monotherapy showed greater improvements in DAS28 (ESR), but similar ACR50 response rates, versus adalimumab monotherapy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Novel approach for image skeleton and distance transformation parallel algorithms

NASA Astrophysics Data System (ADS)

Qing, Kent P.; Means, Robert W.

1994-05-01

Image Understanding is more important in medical imaging than ever, particularly where real-time automatic inspection, screening and classification systems are installed. Skeleton and distance transformations are among the common operations that extract useful information from binary images and aid in Image Understanding. The distance transformation describes the objects in an image by labeling every pixel in each object with the distance to its nearest boundary. The skeleton algorithm starts from the distance transformation and finds the set of pixels that have a locally maximum label. The distance algorithm has to scan the entire image several times depending on the object width. For each pixel, the algorithm must access the neighboring pixels and find the maximum distance from the nearest boundary. It is a computational and memory access intensive procedure. In this paper, we propose a novel parallel approach to the distance transform and skeleton algorithms using the latest VLSI high- speed convolutional chips such as HNC's ViP. The algorithm speed is dependent on the object's width and takes (k + [(k-1)/3]) * 7 milliseconds for a 512 X 512 image with k being the maximum distance of the largest object. All objects in the image will be skeletonized at the same time in parallel.

Impact of a web-based tool (WebCONSORT) to improve the reporting of randomised trials: results of a randomised controlled trial.

PubMed

Hopewell, Sally; Boutron, Isabelle; Altman, Douglas G; Barbour, Ginny; Moher, David; Montori, Victor; Schriger, David; Cook, Jonathan; Gerry, Stephen; Omar, Omar; Dutton, Peter; Roberts, Corran; Frangou, Eleni; Clifton, Lei; Chiocchia, Virginia; Rombach, Ines; Wartolowska, Karolina; Ravaud, Philippe

2016-11-28

The CONSORT Statement is an evidence-informed guideline for reporting randomised controlled trials. A number of extensions have been developed that specify additional information to report for more complex trials. The aim of this study was to evaluate the impact of using a simple web-based tool (WebCONSORT, which incorporates a number of different CONSORT extensions) on the completeness of reporting of randomised trials published in biomedical publications. We conducted a parallel group randomised trial. Journals which endorsed the CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not actively implement it (i.e. require authors to submit a completed CONSORT checklist) were invited to participate. Authors of randomised trials were requested by the editor to use the web-based tool at the manuscript revision stage. Authors registering to use the tool were randomised (centralised computer generated) to WebCONSORT or control. In the WebCONSORT group, they had access to a tool allowing them to combine the different CONSORT extensions relevant to their trial and generate a customised checklist and flow diagram that they must submit to the editor. In the control group, authors had only access to a CONSORT flow diagram generator. Authors, journal editors, and outcome assessors were blinded to the allocation. The primary outcome was the proportion of CONSORT items (main and extensions) reported in each article post revision. A total of 46 journals actively recruited authors into the trial (25 March 2013 to 22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166; control n = 158), of which 197 were reports of randomised trials (n = 94; n = 103). Over a third (39%; n = 127) of registered manuscripts were excluded from the analysis, mainly because the reported study was not a randomised trial. Of those included in the analysis, the most common CONSORT extensions selected were non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n = 10; n = 9). In a quarter of manuscripts, authors either wrongly selected an extension or failed to select the right extension when registering their manuscript on the WebCONSORT study site. Overall, there was no important difference in the overall mean score between WebCONSORT (mean score 0.51) and control (0.47) in the proportion of CONSORT and CONSORT extension items reported pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10). This study failed to show a beneficial effect of a customised web-based CONSORT checklist to help authors prepare more complete trial reports. However, the exclusion of a large number of inappropriately registered manuscripts meant we had less precision than anticipated to detect a difference. Better education is needed, earlier in the publication process, for both authors and journal editorial staff on when and how to implement CONSORT and, in particular, CONSORT-related extensions. ClinicalTrials.gov: NCT01891448 [registered 24 May 2013].

Content-addressable read/write memories for image analysis

NASA Technical Reports Server (NTRS)

Snyder, W. E.; Savage, C. D.

1982-01-01

The commonly encountered image analysis problems of region labeling and clustering are found to be cases of search-and-rename problem which can be solved in parallel by a system architecture that is inherently suitable for VLSI implementation. This architecture is a novel form of content-addressable memory (CAM) which provides parallel search and update functions, allowing speed reductions down to constant time per operation. It has been proposed in related investigations by Hall (1981) that, with VLSI, CAM-based structures with enhanced instruction sets for general purpose processing will be feasible.

Sensitive and label-free detection of miRNA-145 by triplex formation.

PubMed

Aviñó, Anna; Huertas, César S; Lechuga, Laura M; Eritja, Ramon

2016-01-01

The development of new strategies for detecting microRNAs (miRNAs) has become a crucial step in the diagnostic field. miRNA profiles depend greatly on the sample and the analytical platform employed, leading sometimes to contradictory results. In this work, we study the use of modified parallel tail-clamps to detect a miRNA sequence involved in tumor suppression by triplex formation. Thermal denaturing curves and circular dichroism (CD) measurements have been performed to confirm that parallel clamps carrying 8-aminoguanine form the most stable triplex structures with their target miRNA. The modified tail-clamps have been tested as bioreceptors in a surface plasmon resonance (SPR) biosensor for the detection of miRNA-145. The detection limit was improved 2.4 times demonstrating that a stable triplex structure is formed between target miRNA and 8-aminoguanine tail-clamp bioreceptor. This new approach is an essential step toward the label-free and reliable detection of miRNA signatures for diagnostic purposes.

Assessment of the efficacy and safety of eslicarbazepine acetate in acute mania and prevention of recurrence: experience from multicentre, double-blind, randomised phase II clinical studies in patients with bipolar disorder I.

PubMed

Grunze, Heinz; Kotlik, Eduardo; Costa, Raquel; Nunes, Teresa; Falcão, Amílcar; Almeida, Luis; Soares-da-Silva, Patrício

2015-03-15

Eslicarbazepine acetate (ESL) is an anticonvulsant approved as an adjunctive therapy in adults with partial-onset seizures. To evaluate the efficacy, safety and tolerability of ESL in the treatment of acute mania and prevention of recurrence in bipolar disorder I. Two 3-week multicentre, double-blind, randomised, placebo-controlled studies in acute mania (study BIA-2093-203: dose titrated by response, ESL 600-1800mg or 800-2400mg, once-daily; study BIA-2093-204: fixed doses of 600, 1200 and 1800mg, once-daily) were followed by a recurrence prevention study consisting of a 2-week open-label period (900mg, once-daily) continued by a double-blind, parallel-group, fixed dose (300, 900 and 1800mg, once-daily) period for a minimum of 6 months. The primary endpoint was changed from baseline until the end of the 3-week treatment period in Young Mania Rating Scale (YMRS) in studies BIA-2093-203 and BIA-2093-204, and the proportion of patients showing no worsening according to the Clinical Global Impressions - Bipolar Version (CGI-BP) over Part II in study BIA-2093-205. In study BIA-2093-203 (n=160, ITT), neither dose group was statistically different from placebo in the primary endpoint, though the ESL 800-2400mg showed a greater reduction in YMRS score (p=0.0523). CGI-BP score changes for mania and overall bipolar illness indicate a significant improvement in patient symptomatology for the ESL 800-2400mg group (from preceding and worst phase) and for ESL 600-1800mg group (from worst phase only) when compared to placebo. Study BIA-2093-204 (n=38) results were inconclusive due to premature termination caused by recruitment difficulties. In study BIA-2093-205 (n=85, ITT), at least 50% of patients showed no worsening in all treatment groups (p=0.250). ESL adverse events were mostly of mild and moderate intensities and consistent with previously reported observations for ESL. ESL treatment was not significantly different from placebo in manic patients in the primary outcome, but secondary outcomes may be suggestive of efficacy. The recurrence prevention study provides preliminary support for efficacy of ESL in patients recovered from an acute manic episode. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study.

PubMed

Paggiosi, M A; Peel, N; McCloskey, E; Walsh, J S; Eastell, R

2014-12-01

We compared the effects of oral alendronate, ibandronate and risedronate on the central and peripheral skeleton over 2 years. We report differences in effect on the central skeleton but not on the peripheral skeleton. Greater effects were observed for ibandronate (and alendronate) than risedronate at the spine but not the hip. Generally, comparative clinical trials of bisphosphonates have examined changes in bone within central skeletal regions. We have examined the effects of bisphosphonate treatment on the peripheral skeleton. We conducted a 2-year, open-label, parallel randomised control trial of three orally administered bisphosphonates, at their licensed dose, to examine and compare their effects on the peripheral skeleton using multiple modes of measurement. We studied 172 postmenopausal women (53-84 years) who had either a bone mineral density (BMD) T-score of  ≤ -2.5 at the spine and/or total hip or  < -1.0 at either site plus a previous low trauma fracture. Participants were randomised to receive either (i) ibandronate 150 mg/month, (ii) alendronate 70 mg/week or (iii) risedronate 35 mg/week, plus calcium (1,200 mg/day) and vitamin D (800 IU/day), for 2 years. Premenopausal women (33-40 years, n = 226) were studied to monitor device stability. We measured central BMD of the lumbar spine, total hip, total body and forearm using dual-energy X-ray absorptiometry. We measured calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and tibia BMD (using peripheral quantitative computed tomography), finger BMD (using radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables (using quantitative ultrasound). Mixed effects regression models were used to evaluate effects of time and treatment allocation on BMD change. By 2 years, there were significant increases (p < 0.05) in central BMD sites (lumbar spine, total hip). In the peripheral skeleton, only significant changes in calcaneus BMD, 33 % total radius BMD and quantitative ultrasound (QUS)-2 broadband ultrasound attenuation (BUA) were evident for women receiving oral bisphosphonates. The increases in lumbar spine and total body BMD were greater with ibandronate and alendronate than with risedronate. Treatment effects on peripheral measurements did not differ between the three bisphosphonates.

Candesartan versus imidapril in hypertension: a randomised study to assess effects of anti-AT1 receptor autoantibodies.

PubMed

Wei, Fen; Jia, Xiu-Jie; Yu, Su-Qin; Gu, Ye; Wang, Li; Guo, Xiao-Mei; Wang, Min; Zhu, Feng; Cheng, Xiang; Wei, Yu-Miao; Zhou, Zi-Hua; Fu, Micheal; Liao, Yu-Hua

2011-03-01

Anti-angiotensin II receptor subtype 1 (AT1 receptor) autoantibodies have previously been shown in sera of hypertensive patients. This study assessed whether anti-AT1-receptor autoantibody in serum is correlated with the efficacy of an AT1-receptor blocker (ARB; candesartan)-based regimen in hypertensive patients after 8 weeks of treatment. The Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies is a multicentre, randomised, blinded endpoint, open-label, parallel-group comparison clinical trial conducted in five centres in Wuhan, China. Treatment is designed as stepwise added-on therapy to reduce blood pressure (BP) < 140/90 mm Hg. 512 patients with moderate to severe primary hypertension were randomly assigned to an 8-week treatment with either ARB (candesartan)-based regimen (n=257) or ACE inhibitor (imidapril)-based regimen (n=255). Systolic and diastolic BP was reduced significantly in both treatment groups. The candesartan-based regimen achieved a significantly greater systolic BP reduction than imdapril (30.8 ± 10.3 vs 28.8 ± 10.3 mm Hg, p = 0.023). In those anti-AT1 receptor autoantibody-positive hypertensive patients, the mean systolic BP at baseline was higher than in the anti-AT1 receptor autoantibody-negative group (160.5 ± 16.5 vs 156.2 ± 17.7 mm Hg; p = 0.006). The mean BP reduction was greater in the candesartan-based regimen than the imidapril-based regimen (-35.4 ± 9.8/16.9 ± 6.9 vs -29.4 ± 9.8/14.2 ± 6.9 mm Hg; p = 0.000 and 0.002, respectively), and more patients on imidapril required add-on medications to achieve BP control (94% vs 86%; p=0.03). No correlation was observed between the titre of anti-AT1 receptor autoantibody and the efficacy of candesartan-based therapy. In those anti-AT1 receptor autoantibody-negative patients similar BP lowering was reached in the candesartan and the imidapril-based regimens. An ARB-based regimen is more effective in BP lowering than an ACE inhibitor-based regimen in the presence of anti-AT1 receptor autoantibodies. Trial registration number This trial has been registered at http://www.register.clinicaltrials.gov/ (identifier: NCT00360763).

Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.

PubMed

Bottomley, Andrew; Pe, Madeline; Sloan, Jeff; Basch, Ethan; Bonnetain, Franck; Calvert, Melanie; Campbell, Alicyn; Cleeland, Charles; Cocks, Kim; Collette, Laurence; Dueck, Amylou C; Devlin, Nancy; Flechtner, Hans-Henning; Gotay, Carolyn; Greimel, Eva; Griebsch, Ingolf; Groenvold, Mogens; Hamel, Jean-Francois; King, Madeleine; Kluetz, Paul G; Koller, Michael; Malone, Daniel C; Martinelli, Francesca; Mitchell, Sandra A; Moinpour, Carol M; Musoro, Jammbe; O'Connor, Daniel; Oliver, Kathy; Piault-Louis, Elisabeth; Piccart, Martine; Pimentel, Francisco L; Quinten, Chantal; Reijneveld, Jaap C; Schürmann, Christoph; Smith, Ashley Wilder; Soltys, Katherine M; Taphoorn, Martin J B; Velikova, Galina; Coens, Corneel

2016-11-01

Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making. Copyright © 2016 Elsevier Ltd. All rights reserved.

N of 1, two contemporary arm, randomised controlled clinical trial for bilateral epicondylitis: a new study design

PubMed Central

Fante, Claudia Del; Perotti, Cesare; Pavesi, Claudio Francesco; Coscia, Davide; Scotti, Valeria; Tinelli, Carmine

2011-01-01

Objective To investigate the use of a novel study design in analysis of bilateral elbow pain. Design N of 1, two contemporary arm, open label, randomised controlled clinical trial. Setting A clinical epidemiologist at a university hospital in Pavia, Italy. Participants Two elbows with epicondylitis. Interventions Autologous platelet lysate versus “wait and see” strategy. Main outcome measures Visual analogue scale for pain on elbow extension and resisted wrist extension. Results Over six months’ follow-up, the patient experienced bilateral improvement in pain, but higher in the treated arm, with a drop in visual analogue scale for pain from 28 to 4 for right (control) arm (drop of 24 points) and from 67 to 10.5 for left (treated) arm (drop of 56.5 points). Conclusions Platelet lysate might (or might not) work. Competing interests and lack of blinding might be relevant issues in the interpretation of trial results. However, the new study design can be applied to a number of conditions such as bilateral sport or trauma injuries, bilateral otitis, or any condition affecting chiral organs or limbs. PMID:22187187

(2+1)-dimensional spacetimes containing closed timelike curves

NASA Astrophysics Data System (ADS)

Headrick, Matthew P.; Gott, J. Richard, III

1994-12-01

We investigate the global geometries of (2+1)-dimensional spacetimes as characterized by the transformations undergone by tangent spaces upon parallel transport around closed curves. We critically discuss the use of the term ``total energy-momentum'' as a label for such parallel-transport transformations, pointing out several problems with it. We then investigate parallel-transport transformations in the known (2+1)-dimensional spacetimes containing closed timelike curves (CTC's), and introduce a few new such spacetimes. Using the more specific concept of the holonomy of a closed curve, applicable in simply connected spacetimes, we emphasize that Gott's two-particle CTC-containing spacetime does not have a tachyonic geometry. Finally, we prove the following modified version of Kabat's conjecture: if a CTC is deformable to spacelike or null infinity while remaining a CTC, then its parallel-transport transformation cannot be a rotation; therefore its holonomy, if defined, cannot be a rotation other than through a multiple of 2π.

Methodological considerations for a randomised controlled trial of podiatry care in rheumatoid arthritis: lessons from an exploratory trial.

PubMed

Turner, Deborah E; Helliwell, Philip S; Woodburn, James

2007-11-06

Whilst evidence exists to support the use of single treatments such as orthoses and footwear, the effectiveness of podiatry-led care as a complex intervention for patients with rheumatoid arthritis (RA) related foot problems is unknown. The aim of this study was to undertake an exploratory randomised controlled parallel arm clinical trial (RheumAFooT) to inform the design and implementation of a definitive trial and to understand the potential benefits of this care. Patients with a definite diagnosis of RA, stable drug management 3 months prior to entry, and a current history of foot problems (pain, deformity, stiffness, skin or nail lesions, or footwear problems) were recruited from a hospital outpatient rheumatology clinic and randomised to receive 12 months of podiatry treatment or no care. The primary outcome was change in foot health status using the impairment/footwear (LFISIF) and activity limitation/participation restriction (LFISAP) subscales of the Leeds Foot Impact Scale. Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ) score and walking speed (m/s) were also recorded. Of the 80 patients identified, 64 patients were eligible to participate in the pilot and 34 were recruited. 16 patients were randomised to receive podiatry led foot care and 18 received no care. Against a backdrop of stable disease (DAS and HAQ scores), there was a statistically significant between group difference in the change in foot health status for foot impairment (LFISIF) but not activity/participation (LFISAP) or function (walking speed) over 12 months. In the podiatry arm, 1 patient declined treatment following randomisation (did not want additional hospital visits) and 3 self-withdrew (lost to follow-up). Patients received an average of 3 consultations for assessment and treatment comprising routine care for skin and nail lesions (n = 3), foot orthoses (n = 9), footwear referral to the orthotist (n = 5), and ultrasound guided intra-articular steroid injection (n = 1). In this exploratory trial patients were difficult to recruit (stable drug management and co-morbid disease) and retain (lack of benefit/additional treatment burden) but overall the intervention was safe (no adverse reactions). Twelve months of podiatry care maintained but did not improve foot health status. These observations are important for the design and implementation of a definitive randomised controlled trial. ISRCTN: 01982076.

Understanding the cluster randomised crossover design: a graphical illustraton of the components of variation and a sample size tutorial.

PubMed

Arnup, Sarah J; McKenzie, Joanne E; Hemming, Karla; Pilcher, David; Forbes, Andrew B

2017-08-15

In a cluster randomised crossover (CRXO) design, a sequence of interventions is assigned to a group, or 'cluster' of individuals. Each cluster receives each intervention in a separate period of time, forming 'cluster-periods'. Sample size calculations for CRXO trials need to account for both the cluster randomisation and crossover aspects of the design. Formulae are available for the two-period, two-intervention, cross-sectional CRXO design, however implementation of these formulae is known to be suboptimal. The aims of this tutorial are to illustrate the intuition behind the design; and provide guidance on performing sample size calculations. Graphical illustrations are used to describe the effect of the cluster randomisation and crossover aspects of the design on the correlation between individual responses in a CRXO trial. Sample size calculations for binary and continuous outcomes are illustrated using parameters estimated from the Australia and New Zealand Intensive Care Society - Adult Patient Database (ANZICS-APD) for patient mortality and length(s) of stay (LOS). The similarity between individual responses in a CRXO trial can be understood in terms of three components of variation: variation in cluster mean response; variation in the cluster-period mean response; and variation between individual responses within a cluster-period; or equivalently in terms of the correlation between individual responses in the same cluster-period (within-cluster within-period correlation, WPC), and between individual responses in the same cluster, but in different periods (within-cluster between-period correlation, BPC). The BPC lies between zero and the WPC. When the WPC and BPC are equal the precision gained by crossover aspect of the CRXO design equals the precision lost by cluster randomisation. When the BPC is zero there is no advantage in a CRXO over a parallel-group cluster randomised trial. Sample size calculations illustrate that small changes in the specification of the WPC or BPC can increase the required number of clusters. By illustrating how the parameters required for sample size calculations arise from the CRXO design and by providing guidance on both how to choose values for the parameters and perform the sample size calculations, the implementation of the sample size formulae for CRXO trials may improve.

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and Anxiety Depression Scale, and International Physical Activity Questionnaire. This study will provide useful information on the feasibility and acceptability of supervised exercise training in adults with inactive and mildly active Crohn's disease and will inform the design of a subsequent, adequately powered, multi-centre trial. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN13021107). Date registration assigned was 02/12/2015.

Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.

PubMed

Wilcox, Joanne; Waite, Chantelle; Tomlinson, Lyndsey; Driscoll, Joanne; Karim, Asra; Day, Edward; Sharif, Adnan

2016-08-22

Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ).

Quantum-Dot-Based Electrochemical Immunoassay for High-Throughput Screening of the Prostate-Specific Antigen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jun; Liu, Guodong; Wu, Hong

2008-01-01

In this paper, we demonstrate an electrochemical high-throughput sensing platform for simple, sensitive detection of PSA based on QD labels. This sensing platform uses a microplate for immunoreactions and disposable screen-printed electrodes (SPE) for electrochemical stripping analysis of metal ions released from QD labels. With the 96-well microplate, capturing antibodies are conveniently immobilized to the well surface, and the process of immunoreaction is easily controlled. The formed sandwich complexes on the well surface are also easily isolated from reaction solutions. In particular, a microplate-based electrochemical assay can make it feasible to conduct a parallel analysis of several samples or multiplemore » protein markers. This assay offers a number of advantages including (1) simplicity, cost-effectiveness, (2) high sensitivity, (3) capability to sense multiple samples or targets in parallel, and (4) a potentially portable device with an SPE array implanted in the microplate. This PSA assay is sensitive because it uses two amplification processes: (1) QDs as a label for enhancing electrical signal since secondary antibodies are linked to QDs that contain a large number of metal atoms and (2) there is inherent signal amplification for electrochemical stripping analysis—preconcentration of metal ion onto the electrode surface for amplifying electrical signals. Therefore, the high sensitivity of this method, stemming from dual signal amplification via QD labels and pre-concentration, allows low concentration levels to be detected while using small sample volumes. Thus, this QD-based electrochemical detection approach offers a simple, rapid, cost-effective, and high throughput assay of PSA.« less

Probing soil C metabolism in response to temperature: results from experiments and modeling

NASA Astrophysics Data System (ADS)

Dijkstra, P.; Dalder, J.; Blankinship, J.; Selmants, P. C.; Schwartz, E.; Koch, G. W.; Hart, S.; Hungate, B. A.

2010-12-01

C use efficiency (CUE) is one of the least understood aspects of soil C cycling, has a very large effect on soil respiration and C sequestration, and decreases with elevated temperature. CUE is directly related to substrate partitioning over energy production and biosynthesis. The production of energy and metabolic precursors occurs in well-known processes such as glycolysis and Krebs cycle. We have developed a new stable isotope approach using position-specific 13C-labeled metabolic tracers to measure these fundamental metabolic processes in intact soil communities (1). We use this new approach, combined with models of soil metabolic flux patterns, to analyze the response of microbial energy production, biosynthesis, and CUE to temperature. The method consists of adding small but precise amounts of position-specific 13C -labeled metabolic tracers to parallel soil incubations, in this case 1-13C and 2,3-13C pyruvate and 1-13C and U-13C glucose. The measurement of CO2 released from the labeled tracers is used to calculate the C flux rates through various metabolic pathways. A simplified metabolic model consisting of 23 reactions is iteratively solved using results of the metabolic tracer experiments and information on microbial precursor demand under different temperatures. This new method enables direct study of fundamental aspects of microbial energy production, C use efficiency, and soil organic matter formation in response to temperature. (1) Dijkstra P, Blankinship JC, Selmants PC, Hart SC, Koch GW, Schwarz E and Hungate BA. Probing metabolic flux patterns of soil microbial communities using parallel position-specific tracer labeling. Soil Biology and Biochemistry (accepted)

Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy.

PubMed

Launer, Lenore J; Miller, Michael E; Williamson, Jeff D; Lazar, Ron M; Gerstein, Hertzel C; Murray, Anne M; Sullivan, Mark; Horowitz, Karen R; Ding, Jingzhong; Marcovina, Santica; Lovato, Laura C; Lovato, James; Margolis, Karen L; O'Connor, Patrick; Lipkin, Edward W; Hirsch, Joy; Coker, Laura; Maldjian, Joseph; Sunshine, Jeffrey L; Truwit, Charles; Davatzikos, Christos; Bryan, R Nick

2011-11-01

People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus standard glycaemic control. The Memory in Diabetes (MIND) study was done in 52 clinical sites in North America as part of Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two factorial parallel group randomised trial. Participants (aged 55-80 years) with type 2 diabetes, high glycated haemoglobin A(1c) (HbA(1c)) concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive glycaemic control targeting HbA(1c) to less than 6·0% (42 mmol/mol) or a standard strategy targeting HbA(1c) to 7·0-7·9% (53-63 mmol/mol). Randomisation was via a centralised web-based system and treatment allocation was not masked from clinic staff or participants. We assessed our cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months. We assessed total brain volume (TBV), our primary brain structure outcome, with MRI at baseline and 40 months in a subset of participants. We included all participants with follow-up data in our primary analyses. In February, 2008, raised mortality risk led to the end of the intensive treatment and transition of those participants to standard treatment. We tested our cognitive function hypotheses with a mixed-effects model that incorporated information from both the 20 and 40 month outcome measures. We tested our MRI hypotheses with an ANCOVA model that included intracranial volume and factors used to stratify randomisation. This study is registered with ClinicalTrials.gov, number NCT00182910. We consecutively enrolled 2977 patients (mean age 62·5 years; SD 5·8) who had been randomly assigned to treatment groups in the ACCORD study. Our primary cognitive analysis was of patients with a 20-month or 40-month DSST score: 1378 assigned to receive intensive treatment and 1416 assigned to receive standard treatment. Of the 614 patients with a baseline MRI, we included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in our primary MRI analysis at 40 months. There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95% CI -0·28 to 0·91; p=0·2997). The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007). Although significant differences in TBV favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants. US National Institute on Aging and US National Heart, Lung, and Blood Institute. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of pre-course e-learning prior to advanced life support training: a randomised controlled trial.

PubMed

Perkins, Gavin D; Fullerton, James N; Davis-Gomez, Nicole; Davies, Robin P; Baldock, Catherine; Stevens, Harry; Bullock, Ian; Lockey, Andrew S

2010-07-01

The role of e-learning in contemporary healthcare education is quickly developing. The aim of this study was to examine the relationship between the use of an e-learning simulation programme (Microsim, Laerdal, UK) prior to attending an Advanced Life Support (ALS) course and the subsequent relationship to candidate performance. An open label, multi-centre randomised controlled study was conducted. The control group received a course manual and pre-course MCQ four weeks prior to the face to face course. The intervention group in addition received the Microsim programme on a CD. The primary outcome was performance during a simulated cardiac arrest at the end of the course. Secondary outcomes were performance during multiple choice exams, resuscitation skills assessments and feedback to Microsim programme. 572 participants were randomised (287 Microsim, 285 control). There were no significant differences in the primary outcome (performance during a standard cardiac arrest simulation) or secondary outcomes. User evaluations were favorable. 79% would recommend it to colleagues. 9% stated Microsim could replace the entire ALS course, 25% parts. Over 70% of participants' perceived that Microsim improved their understanding of the key learning domains of the ALS course. Distributing Microsim to healthcare providers prior to attending an ALS courses did not improve either cognitive or psychomotor skills performance during cardiac arrest simulation testing. The challenge that lies ahead is to identify the optimal way to use e-learning as part of a blended approach to learning for this type of training programme.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

PubMed

Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

2016-11-01

Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial.

PubMed

Mayfield, Karla; Siskind, Dan; Winckel, Karl; Hollingworth, Samantha; Kisely, Steve; Russell, Anthony W

2015-06-01

Clozapine causes significant metabolic disturbances including obesity and type 2 diabetes. Recent evidence that reduced glucagon-like-peptide-1 (GLP-1) may contribute to aetiology of clozapine-associated metabolic dysregulation suggests a potential therapeutic role for GLP-1 agonists. This open-label, pilot randomised controlled trial evaluates the effect of exenatide in clozapine-treated obese adults who have schizophrenia, with or without poorly controlled diabetes. Sixty out-patients will be randomised to once weekly extended release exenatide or treatment as usual for 24 weeks. To evaluate the feasibility of larger studies regarding methodology, acceptability, tolerability and estimate efficacy for glycaemic control or weight loss. Secondary outcomes are psychosis severity and metabolic parameters. This is the first trial investigating GLP-1 agonists for glycaemic control and weight loss in clozapine-treated patients with either diabetes or obesity. Clozapine-associated obesity and diabetes with exenatide (CODEX) will provide proof-of-concept empirical evidence addressing whether this novel treatment is practical and worthy of further investigation. A.W.R. has received speaker honoraria and travel grants from AstraZeneca, BoehringerIngelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and has participated on advisory panels for MSD and Novo Nordisk. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

PubMed

Dass, S; Bowman, S J; Vital, E M; Ikeda, K; Pease, C T; Hamburger, J; Richards, A; Rauz, S; Emery, P

2008-11-01

Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Randomised controlled clinical trial of increased dose and frequency of albendazole and ivermectin on Wuchereria bancrofti microfilarial clearance in northern Malawi.

PubMed

Tafatatha, Terence T; Ngwira, Bagrey M; Taegtmeyer, Miriam; Phiri, Amos J; Wilson, Trevor P; Banda, Louis G; Piston, Wilson N; Koole, Olivier; Horton, John; French, Neil

2015-06-01

In Africa, albendazole and ivermectin are currently used in combination for annual mass drug administration (MDA) for lymphatic filariasis (LF) elimination. Rapid and sustained clearance is desirable for public health impact and elimination of LF. Increasing the dose and/or frequency of albendazole and ivermectin treatment may be more effective in clearing microfilariae than standard MDA. We conducted a randomised controlled open label trial in northern Malawi comparing three modified treatment groups to standard dosage of ivermectin and albendazole in adults with confirmed circulating LF antigen and microfilaria. Participants were followed-up every 6 months for 2 years for repeat microfilarial counts and safety assessments. A total of 1851 adults were screened and 70 with microfilarial counts >80 microfilariae/ml were randomised. All treatment groups achieved a significant reduction of microfilariae levels by 12- and 24-months of follow-up. Doubling the standard dose and administering it twice yearly showed a non-significant tendency towards faster and more complete clearance. There were no serious adverse reactions. In this small study, all regimens effectively cleared microfilaria. Standard treatment may be adequate in settings like Malawi but not in all endemic settings and larger studies are required to demonstrate benefit of higher dosages. [ClinicalTrials.gov identifier: NCT01213576]. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the Highlow study, a randomised trial of two doses.

PubMed

Bleker, Suzanne M; Buchmüller, Andrea; Chauleur, Céline; Ní Áinle, Fionnuala; Donnelly, Jennifer; Verhamme, Peter; Jacobsen, Anne Flem; Ganzevoort, Wessel; Prins, Martin; Beyer-Westendorf, Jan; DeSancho, Maria; Konstantinides, Stavros; Pabinger, Ingrid; Rodger, Marc; Decousus, Hervé; Middeldorp, Saskia

2016-08-01

Women with a history of venous thromboembolism (VTE) have a 2% to 10% absolute risk of VTE recurrence during subsequent pregnancies. Therefore, current guidelines recommend that all pregnant women with a history of VTE receive pharmacologic thromboprophylaxis. The optimal dose of low-molecular-weight heparin (LMWH) for thromboprophylaxis is unknown. In the Highlow study (NCT 01828697; www.highlowstudy.org), we compare a fixed low dose of LMWH with an intermediate dose of LMWH for the prevention of pregnancy-associated recurrent VTE. We present the rationale and design features of this study. The Highlow study is an investigator-initiated, multicentre, international, open-label, randomised trial. Pregnant women with a history of VTE and an indication for ante- and postpartum pharmacologic thromboprophylaxis are included before 14weeks of gestation. The primary efficacy outcome is symptomatic recurrent VTE during pregnancy and 6weeks postpartum. The primary safety outcomes are clinically relevant bleeding, blood transfusions before 6weeks postpartum and mortality. Patients are closely monitored to detect cutaneous reactions to LMWH and are followed for 3months after delivery. A central independent adjudication committee adjudicates all suspected outcome events. The Highlow study is the first large randomised controlled trial in pregnancy that will provide high-quality evidence on the optimal dose of LWMH thromboprophylaxis for the prevention of recurrent VTE in pregnant women with a history of VTE. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial.

PubMed

de Bruin, Marijn; Oberjé, Edwin J M; Viechtbauer, Wolfgang; Nobel, Hans-Erik; Hiligsmann, Mickaël; van Nieuwkoop, Cees; Veenstra, Jan; Pijnappel, Frank J; Kroon, Frank P; van Zonneveld, Laura; Groeneveld, Paul H P; van Broekhuizen, Marjolein; Evers, Silvia M A A; Prins, Jan M

2017-06-01

No high-quality trials have provided evidence of effectiveness and cost-effectiveness of HIV treatment adherence intervention strategies. We therefore examined the effectiveness and cost-effectiveness of the Adherence Improving self-Management Strategy (AIMS) compared with treatment as usual. We did a pragmatic, multicentre, open-label, randomised controlled trial in seven HIV clinics at academic and non-academic hospitals in the Netherlands. Eligible participants were patients with HIV who were either treatment experienced (ie, with ≥9 months on combination antiretroviral therapy [ART] and at risk of viral rebound) or treatment-naive patients initiating their first combination ART regimen. We randomly assigned participants (1:1) to either AIMS or treatment as usual (ie, containing a range of common adherence intervention strategies) using a computer-generated randomisation table. Randomisation was stratified by treatment experience (experienced vs naive) and included block randomisation at nurse level with randomly ordered blocks of size four, six, and eight. 21 HIV nurses from the participating clinics received three training sessions of 6 h each (18 h in total) on AIMS and a 1·5 h booster training session at the clinic (two to three nurses per session) after each nurse had seen two to three patients. AIMS was delivered by nurses during routine clinic visits. We did mixed-effects, intent-to-treat analyses to examine treatment effects on the primary outcome of log 10 viral load collected at months 5, 10, and 15. The viral load results were exponentiated (with base 10) for easier interpretation. Using cohort data from 7347 Dutch patients with HIV to calculate the natural course of illness, we developed a lifetime Markov model to estimate the primary economic outcome of lifetime societal costs per quality-adjusted life-years (QALYs) gained. This trial is registered at ClinicalTrials.gov (number NCT01429142). We recruited participants between Sept 1, 2011, and April 2, 2013; the last patient completed the study on June 16, 2014. The intent-to-treat sample comprised 221 patients; 109 assigned to AIMS and 112 to treatment as usual. Across the three timepoints (months 5, 10, and 15), log viral load was 1·26 times higher (95% CI 1·04-1·52) in the treatment-as-usual group (estimated marginal mean 44·5 copies per mL [95% CI 35·5-55·9]) than in the AIMS group (estimated marginal mean 35·4 copies per mL [29·9-42·0]). Additionally, AIMS was cost-effective (ie, dominant: cheaper and more effective) since it reduced lifetime societal costs by €592 per patient and increased QALYs by 0·034 per patient. Findings from preparatory studies have shown that AIMS is acceptable, feasible to deliver in routine care, and has reproducible effects on medication adherence. In this study, AIMS reduced viral load, increased QALYs, and saved resources. Implementation of AIMS in routine clinical HIV care is therefore recommended. Netherlands Organisation for Health Research and Development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

PubMed

Bernard, Louis; Dinh, Aurélien; Ghout, Idir; Simo, David; Zeller, Valerie; Issartel, Bertrand; Le Moing, Vincent; Belmatoug, Nadia; Lesprit, Philippe; Bru, Jean-Pierre; Therby, Audrey; Bouhour, Damien; Dénes, Eric; Debard, Alexa; Chirouze, Catherine; Fèvre, Karine; Dupon, Michel; Aegerter, Philippe; Mulleman, Denis

2015-03-07

Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis. In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physician's choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114. Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]). 6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks. French Ministry of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

PubMed

Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

2017-04-01

Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AF randomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4-14·5, p=0·002; number needed to screen 11). Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). Boehringer Ingelheim. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study.

PubMed

Merrill, Joan T; Wallace, Daniel J; Petri, Michelle; Kirou, Kyriakos A; Yao, Yihong; White, Wendy I; Robbie, Gabriel; Levin, Robert; Berney, Seth M; Chindalore, Vishala; Olsen, Nancy; Richman, Laura; Le, Chenxiong; Jallal, Bahija; White, Barbara

2011-11-01

Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets. Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE. received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days. Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014). Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE. Trial registration number NCT00299819.

Sustained glycaemic control and less nocturnal hypoglycaemia with insulin glargine 300U/mL compared with glargine 100U/mL in Japanese adults with type 1 diabetes (EDITION JP 1 randomised 12-month trial including 6-month extension).

PubMed

Matsuhisa, Munehide; Koyama, Masayoshi; Cheng, Xi; Sumi, Mariko; Riddle, Matthew C; Bolli, Geremia B; Hirose, Takahisa

2016-12-01

To evaluate the efficacy and safety of insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in adults with type 1 diabetes in Japan over 12months. EDITION JP 1 was a multicentre, randomised, open-label phase 3 study. Following a 6-month on-treatment period, participants continued to receive Gla-300 or Gla-100 once daily, plus mealtime insulin, over a 6-month open-label extension phase. HbA1c, hypoglycaemia, body weight and adverse events were assessed. Overall, 114/122 (93%) and 114/121 (94%) of participants in the Gla-300 and Gla-100 group, respectively, completed the 6-month extension phase. Glycaemic control was sustained in both groups up to month 12 (mean HbA1c: Gla-300, 7.9% [62mmol/mol]; Gla-100, 7.8% [62mmol/mol]). Annualised rates of hypoglycaemia were lower with Gla-300 versus Gla-100; significantly for nocturnal confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia (2.39 and 3.85 events per participant-year; rate ratio: 0.62 [0.39-0.97]). No between-treatment differences in mean body weight change or adverse events were observed. Over 12months' treatment, participants with type 1 diabetes receiving Gla-300 achieved sustained glycaemic control and experienced less nocturnal hypoglycaemia that was confirmed (<3.0mmol/L [<54mg/dL]) or severe compared with Gla-100, supporting the 6-month results. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

PubMed

Armoiry, X; Kan, A; Melendez-Torres, G J; Court, R; Sutcliffe, P; Auguste, P; Madan, J; Counsell, C; Clarke, A

2018-05-01

Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. Meta-analyses confirmed that IFN-β and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

Challenge with a hepatitis B vaccine in two cohorts of 4-7-year-old children primed with hexavalent vaccines: an open-label, randomised trial in Italy.

PubMed

Zanetti, Alessandro; Parlato, Antonino; Romanò, Luisa; Desole, Maria Giuseppina; Ferrera, Giuseppe; Giurdanella, Filippo; Zuliani, Massimo; Richard, Patrick; Thomas, Stéphane; Fiquet, Anne

2012-08-24

The anamnestic response to a challenge dose of vaccine can assess immune memory and protection against hepatitis B infection. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children immunised with three doses of either Hexavac or Infanrix-Hexa during infancy. This open-label, randomised, controlled, four-arm study enrolled 410 healthy children aged 4-7 years who had received either Hexavac (n=201) or Infanrix-Hexa (n=209) at 3, 5 and 11 months of life. Children received a single intramuscular challenge dose of either hepatitis B vaccine, HBVaxPro (Hexavac, n=34; Infanrix-Hexa, n=28) or Engerix-B (Hexavac, n=167; Infanrix-Hexa, n=181). Hepatitis B surface antibody (anti-HBs) concentrations were measured before and 1 month after the challenge vaccine dose. The analysis was descriptive and no formal hypothesis was tested. One month post-challenge, 91.2% of children in the Hexavac group (95% confidence interval [CI] 86.3, 94.8) and 98.0% (95% CI 94.9, 99.4) in the Infanrix-Hexa group had anti-HBs concentrations ≥10 mIU/ml (primary endpoint). In a post hoc analysis, most children with pre-challenge anti-HBs concentration <10 mIU/ml achieved anti-HBs concentrations ≥10 mIU/ml (Hexavac group, 85.3% [95% CI 77.6, 91.2]; Infanrix-Hexa group, 91.9% [95% CI 78.1, 98.3]). Both challenge vaccines were well tolerated. These data suggest that immune memory persists for long-term (5 years) after a primary vaccination in infancy with a hexavalent vaccine (Hexavac or Infanrix-Hexa). Copyright © 2012 Elsevier Ltd. All rights reserved.

Staphylococcus aureus Peptidoglycan Stem Packing by Rotational-Echo Double Resonance NMR Spectroscopy

PubMed Central

Kim, Sung Joon; Singh, Manmilan; Preobrazhenskaya, Maria; Schaefer, Jacob

2013-01-01

Staphylococcus aureus grown in the presence of an alanine-racemase inhibitor was labeled with D-[1-13C]alanine and L-[15N]alanine to characterize some details of the peptidoglycan tertiary structure. Rotational-echo double-resonance NMR of intact whole cells was used to measure internuclear distances between 13C and 15N of labeled amino acids incorporated in the peptidoglycan, and from those labels to 19F of a glycopeptide drug specifically bound to the peptidoglycan. The observed 13C-15N average distance of 4.1 to 4.4 Å between D- and L-alanines in nearest-neighbor peptide stems is consistent with a local, tightly packed, parallel-stem architecture for a repeating structural motif within the peptidoglycan of S. aureus. PMID:23617832

Immunocytochemistry by electron spectroscopic imaging using a homogeneously boronated peptide.

PubMed

Kessels, M M; Qualmann, B; Klobasa, F; Sierralta, W D

1996-05-01

A linear all-L-oligopeptide containing five carboranyl amino acids (corresponding to 50 boron atoms) was synthesized and specifically attached to the free thiol group of monovalent antibody fragments F(ab)'. The boronated immunoreagent was used for the direct post-embedding detection of somatotrophic hormone in ultrathin sections of porcine pituitary embedded in Spurr resin. The specific boron-labelling of secretory vesicles in somatotrophs was detected by electron spectroscopic imaging and confirmed by conventional immunogold labelling run in parallel. In comparison with immunogold, boron-labelled F(ab)'-fragments showed higher tagging frequencies, as was expected; the small uncharged immunoreagents have an elongated shape and carry the antigen-combining structure and the detection tag at opposite ends, thus allowing for high spatial resolution in electron spectroscopic imaging.

Quantifying Drosophila food intake: comparative analysis of current methodology

PubMed Central

Deshpande, Sonali A.; Carvalho, Gil B.; Amador, Ariadna; Phillips, Angela M.; Hoxha, Sany; Lizotte, Keith J.; Ja, William W.

2014-01-01

Food intake is a fundamental parameter in animal studies. Despite the prevalent use of Drosophila in laboratory research, precise measurements of food intake remain challenging in this model organism. Here, we compare several common Drosophila feeding assays: the Capillary Feeder (CAFE), food-labeling with a radioactive tracer or a colorimetric dye, and observations of proboscis extension (PE). We show that the CAFE and radioisotope-labeling provide the most consistent results, have the highest sensitivity, and can resolve differences in feeding that dye-labeling and PE fail to distinguish. We conclude that performing the radiolabeling and CAFE assays in parallel is currently the best approach for quantifying Drosophila food intake. Understanding the strengths and limitations of food intake methodology will greatly advance Drosophila studies of nutrition, behavior, and disease. PMID:24681694

Rapid Covalent Fluorescence Labeling of Membrane Proteins on Live Cells via Coiled-Coil Templated Acyl Transfer.

PubMed

Reinhardt, Ulrike; Lotze, Jonathan; Mörl, Karin; Beck-Sickinger, Annette G; Seitz, Oliver

2015-10-21

Fluorescently labeled proteins enable the microscopic imaging of protein localization and function in live cells. In labeling reactions targeted against specific tag sequences, the size of the fluorophore-tag is of major concern. The tag should be small to prevent interference with protein function. Furthermore, rapid and covalent labeling methods are desired to enable the analysis of fast biological processes. Herein, we describe the development of a method in which the formation of a parallel coiled coil triggers the transfer of a fluorescence dye from a thioester-linked coil peptide conjugate onto a cysteine-modified coil peptide. This labeling method requires only small tag sequences (max 23 aa) and occurs with high tag specificity. We show that size matching of the coil peptides and a suitable thioester reactivity allow the acyl transfer reaction to proceed within minutes (rather than hours). We demonstrate the versatility of this method by applying it to the labeling of different G-protein coupled membrane receptors including the human neuropeptide Y receptors 1, 2, 4, 5, the neuropeptide FF receptors 1 and 2, and the dopamine receptor 1. The labeled receptors are fully functional and able to bind the respective ligand with high affinity. Activity is not impaired as demonstrated by activation, internalization, and recycling experiments.

Elder and Child Abuse: Conceptual and Perceptual Parallels.

ERIC Educational Resources Information Center

Utech, Myron R.; Garrett, Robert R.

1992-01-01

Reviews the meaning and uses of elder-abuse and child-abuse concepts and percepts in the reporting of events and research. Reports that the stereotypical nature of the concepts and the labeling of the victims has hampered the reporting of the maltreatment, thus impairing the accuracy of the research. (RJM)

The second Symptom Management Research Trial in Oncology (SMaRT Oncology-2): a randomised trial to determine the effectiveness and cost-effectiveness of adding a complex intervention for major depressive disorder to usual care for cancer patients.

PubMed

Walker, Jane; Cassidy, Jim; Sharpe, Michael

2009-03-30

Depression Care for People with Cancer is a complex intervention delivered by specially trained cancer nurses, under the supervision of a psychiatrist. It is given as a supplement to the usual care for depression, which patients receive from their general practitioner and cancer service. In a 'proof of concept' trial (Symptom Management Research Trials in Oncology-1) Depression Care for People with Cancer improved depression more than usual care alone. The second Symptom Management Research Trial in Oncology (SMaRT Oncology-2 Trial) will test its effectiveness and cost-effectiveness in a 'real world' setting. A two arm parallel group multi-centre randomised controlled trial. TRIAL PROCEDURES: 500 patients will be recruited through established systematic Symptom Monitoring Services, which screen patients for depression. Patients will have: a diagnosis of cancer (of various types); an estimated life expectancy of twelve months or more and a diagnosis of Major Depressive Disorder. Patients will be randomised to usual care or usual care plus Depression Care for People with Cancer. Randomisation will be carried out by telephoning a secure computerised central randomisation system or by using a secure web interface. The primary outcome measure is 'treatment response' measured at 24 week outcome data collection. 'Treatment response' will be defined as a reduction of 50% or more in the patient's baseline depression score, measured using the 20-item Symptom Checklist (SCL-20D). Secondary outcomes include remission of major depressive disorder, depression severity and patients' self-rated improvement of depression. Current controlled trials ISRCTN40568538 TRIAL HYPOTHESES: (1) Depression Care for People with Cancer as a supplement to usual care will be more effective than usual care alone in achieving a 50% reduction in baseline SCL-20D score at 24 weeks. (2) Depression Care for People with Cancer as a supplement to usual care will cost more than usual care alone but will be more cost effective in achieving improvements in patients' depression and quality of life.

Oral versus intravenous antibiotic treatment for bone and joint infections (OVIVA): study protocol for a randomised controlled trial.

PubMed

Li, Ho Kwong; Scarborough, Matthew; Zambellas, Rhea; Cooper, Cushla; Rombach, Ines; Walker, A Sarah; Lipsky, Benjamin A; Briggs, Andrew; Seaton, Andrew; Atkins, Bridget; Woodhouse, Andrew; Berendt, Anthony; Byren, Ivor; Angus, Brian; Pandit, Hemant; Stubbs, David; McNally, Martin; Thwaites, Guy; Bejon, Philip

2015-12-21

Bone and joint infection in adults arises most commonly as a complication of joint replacement surgery, fracture fixation and diabetic foot infection. The associated morbidity can be devastating to patients and costs the National Health Service an estimated £20,000 to £40,000 per patient. Current standard of care in most UK centres includes a prolonged course (4-6 weeks) of intravenous antibiotics supported, if available, by an outpatient parenteral antibiotic therapy service. Intravenous therapy carries with it substantial risks and inconvenience to patients, and the antibiotic-related costs are approximately ten times that of oral therapy. Despite this, there is no evidence to suggest that oral therapy results in inferior outcomes. We hypothesise that, by selecting oral agents with high bioavailability, good tissue penetration and activity against the known or likely pathogens, key outcomes in patients managed primarily with oral therapy are non-inferior to those in patients treated by intravenous therapy. The OVIVA trial is a parallel group, randomised (1:1), un-blinded, non-inferiority trial conducted in thirty hospitals across the UK. Eligible participants are adults (>18 years) with a clinical syndrome consistent with a bone, joint or metalware-associated infection who have received ≤7 days of intravenous antibiotic therapy from the date of definitive surgery (or the start of planned curative therapy in patients treated without surgical intervention). Participants are randomised to receive either oral or intravenous antibiotics, selected by a specialist infection physician, for the first 6 weeks of therapy. The primary outcome measure is definite treatment failure within one year of randomisation, as assessed by a blinded endpoint committee, according to pre-defined microbiological, histological and clinical criteria. Enrolling 1,050 subjects will provide 90 % power to demonstrate non-inferiority, defined as less than 7.5 % absolute increase in treatment failure rate in patients randomised to oral therapy as compared to intravenous therapy (one-sided alpha of 0.05). If our results demonstrate non-inferiority of orally administered antibiotic therapy, this trial is likely to facilitate a dramatically improved patient experience and alleviate a substantial financial burden on healthcare services. ISRCTN91566927 - 14/02/2013.

Effect of Baduanjin exercise on cognitive function in older adults with mild cognitive impairment: study protocol for a randomised controlled trial.

PubMed

Zheng, Guohua; Huang, Maomao; Li, Shuzhen; Li, Moyi; Xia, Rui; Zhou, Wenji; Tao, Jing; Chen, Lidian

2016-04-11

Mild cognitive impairment (MCI) is an intermediate stage between the cognitive changes of normal aging and dementia characterised by a reduction in memory and/or other cognitive processes. An increasing number of studies have indicated that regular physical activity/exercise may have beneficial association with cognitive function of older adults with or without cognitive impairment. As a traditional Chinese Qigong exercise, Baduanjin may be even more beneficial in promoting cognitive ability in older adults with MCI, but the evidence is still insufficient. The main purpose of this study is to investigate the effect of Baduanjin exercise on neuropsychological outcomes of community-dwelling older adults with MCI, and to explore its mechanism of action from neuroimaging based on functional MRI (fMRI) and cerebrovascular function. The design of this study is a randomised, controlled trial with three parallel groups in a 1:1:1 allocation ratio with allocation concealment and assessor blinding. A total of 135 participants will be enrolled and randomised to the 24-week Baduanjin exercise intervention, 24-week brisk walking intervention and 24-week usual physical activity control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 9, 17, 25 and 37 weeks after randomisation, while the structure and function of brain regions related to cognitive function and haemodynamic variables of the brain will be measured by fMRI and transcranial Doppler, respectively, at baseline and 25 and 37 weeks after randomisation. Ethics approval was given by the Medical Ethics Committee of the Second People's Hospital of Fujian Province (approval number 2014-KL045-02). The findings will be disseminated through peer-reviewed publications and at scientific conferences. ChiCTR-ICR-15005795; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The evaluation of enhanced feedback interventions to reduce unnecessary blood transfusions (AFFINITIE): protocol for two linked cluster randomised factorial controlled trials.

PubMed

Hartley, Suzanne; Foy, Robbie; Walwyn, Rebecca E A; Cicero, Robert; Farrin, Amanda J; Francis, Jill J; Lorencatto, Fabiana; Gould, Natalie J; Grant-Casey, John; Grimshaw, Jeremy M; Glidewell, Liz; Michie, Susan; Morris, Stephen; Stanworth, Simon J

2017-07-03

Blood for transfusion is a frequently used clinical intervention, and is also a costly and limited resource with risks. Many transfusions are given to stable and non-bleeding patients despite no clear evidence of benefit from clinical studies. Audit and feedback (A&F) is widely used to improve the quality of healthcare, including appropriate use of blood. However, its effects are often inconsistent, indicating the need for coordinated research including more head-to-head trials comparing different ways of delivering feedback. A programmatic series of research projects, termed the 'Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE' (AFFINITIE) programme, aims to test different ways of developing and delivering feedback within an existing national audit structure. The evaluation will comprise two linked 2×2 factorial, cross-sectional cluster-randomised controlled trials. Each trial will estimate the effects of two feedback interventions, 'enhanced content' and 'enhanced follow-on support', designed in earlier stages of the AFFINITIE programme, compared to current practice. The interventions will be embedded within two rounds of the UK National Comparative Audit of Blood Transfusion (NCABT) focusing on patient blood management in surgery and use of blood transfusions in patients with haematological malignancies. The unit of randomisation will be National Health Service (NHS) trust or health board. Clusters providing care relevant to the audit topics will be randomised following each baseline audit (separately for each trial), with stratification for size (volume of blood transfusions) and region (Regional Transfusion Committee). The primary outcome for each topic will be the proportion of patients receiving a transfusion coded as unnecessary. For each audit topic a linked, mixed-method fidelity assessment and cost-effectiveness analysis will be conducted in parallel to the trial. AFFINITIE involves a series of studies to explore how A&F may be refined to change practice including two cluster randomised trials linked to national audits of transfusion practice. The methodology represents a step-wise increment in study design to more fully evaluate the effects of two enhanced feedback interventions on patient- and trust-level clinical, cost, safety and process outcomes. http://www.isrctn.com/ISRCTN15490813.

Extra Physiotherapy in Critical Care (EPICC) Trial Protocol: a randomised controlled trial of intensive versus standard physical rehabilitation therapy in the critically ill.

PubMed

Thomas, Kirsty; Wright, Stephen E; Watson, Gillian; Baker, Catherine; Stafford, Victoria; Wade, Clare; Chadwick, Thomas J; Mansfield, Leigh; Wilkinson, Jennifer; Shen, Jing; Deverill, Mark; Bonner, Stephen; Hugill, Keith; Howard, Philip; Henderson, Andrea; Roy, Alistair; Furneval, Julie; Baudouin, Simon V

2015-05-25

Patients discharged from Critical Care suffer from excessive longer term morbidity and mortality. Physical and mental health measures of quality of life show a marked and immediate fall after admission to Critical Care with some recovery over time. However, physical function is still significantly reduced at 6 months. The National Institute for Health and Care Excellence clinical guideline on rehabilitation after critical illness, identified the need for high-quality randomised controlled trials to determine the most effective rehabilitation strategy for critically ill patients at risk of critical illness-associated physical morbidity. In response to this, we will conduct a randomised controlled trial, comparing physiotherapy aimed at early and intensive patient mobilisation with routine care. We hypothesise that this intervention will improve physical outcomes and the mental health and functional well-being of survivors of critical illness. 308 adult patients who have received more than 48 h of non-invasive or invasive ventilation in Critical Care will be recruited to a patient-randomised, parallel group, controlled trial, comparing two intensities of physiotherapy. Participants will be randomised to receive either standard or intensive physiotherapy for the duration of their Critical Care admission. Outcomes will be recorded on Critical Care discharge, at 3 and 6 months following initial recruitment to the study. The primary outcome measure is physical health at 6 months, as measured by the SF-36 Physical Component Summary. Secondary outcomes include assessment of mental health, activities of daily living, delirium and ventilator-free days. We will also include a health economic analysis. The trial has ethical approval from Newcastle and North Tyneside 2 Research Ethics Committee (11/NE/0206). There is a Trial Oversight Committee including an independent chair. The results of the study will be submitted for publication in peer-reviewed journals and presented at national and international scientific meetings. ISRCTN20436833. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study.

PubMed

Matsuoka, Hiromichi; Ishiki, Hiroto; Iwase, Satoru; Koyama, Atsuko; Kawaguchi, Takashi; Kizawa, Yoshiyuki; Morita, Tatsuya; Matsuda, Yoshinobu; Miyaji, Tempei; Ariyoshi, Keisuke; Yamaguchi, Takuhiro

2017-08-28

Management of patients with cancer suffering from neuropathic pain refractory to opioids and gabapentinoids remains an important challenge. Duloxetine is one of the choices after first-line treatment fails. The efficacy of duloxetine has been reported in patients with non-cancer disease and in chemotherapy-induced peripheral neuropathy, but no randomised clinical trials have examined its effects on neuropathic cancer pain refractory to first-line treatment. The objective of this study is to assess the analgesic efficacy of duloxetine in patients suffering from neuropathic cancer pain refractory to opioids and gabapentinoids. A multi-institutional, prospective, randomised, double-blind, placebo-controlled, two-parallel trial is planned. The inclusion criteria are adult patients with cancer suffering from neuropathic cancer pain refractory to opioids and gabapentinoids, patients with a Numerical Rating Scale (NRS) pain score of 4 or higher and patients with a total Hospital Anxiety and Depression Scale score of less than 20. Patients with chemotherapy-induced peripheral neuropathy are excluded. The study will take place at 14 sites across Japan. Participants will be randomised (1:1 allocation ratio) to a duloxetine intervention group or a placebo control group. Evaluations will be made at baseline (T0 randomisation), day 0 (T1), day 3 (T2) and day 10 (T3). The primary endpoint is defined as the difference in NRS score for pain intensity (average over the previous 24 hours) at T3 between the duloxetine and placebo groups. A sample size of 70 patients will be examined between July 2015 and March 2018. Ethics approval was obtained at all participating sites.The results of this study will be submitted for publication in international peer-reviewed journals and the key findings presented at international scientific conferences. UMIN000017647; Pre-results. 2.2, 26 April 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intervention for children with word-finding difficulties: a parallel group randomised control trial.

PubMed

Best, Wendy; Hughes, Lucy Mari; Masterson, Jackie; Thomas, Michael; Fedor, Anna; Roncoli, Silvia; Fern-Pollak, Liory; Shepherd, Donna-Lynn; Howard, David; Shobbrook, Kate; Kapikian, Anna

2017-07-31

The study investigated the outcome of a word-web intervention for children diagnosed with word-finding difficulties (WFDs). Twenty children age 6-8 years with WFDs confirmed by a discrepancy between comprehension and production on the Test of Word Finding-2, were randomly assigned to intervention (n = 11) and waiting control (n = 9) groups. The intervention group had six sessions of intervention which used word-webs and targeted children's meta-cognitive awareness and word-retrieval. On the treated experimental set (n = 25 items) the intervention group gained on average four times as many items as the waiting control group (d = 2.30). There were also gains on personally chosen items for the intervention group. There was little change on untreated items for either group. The study is the first randomised control trial to demonstrate an effect of word-finding therapy with children with language difficulties in mainstream school. The improvement in word-finding for treated items was obtained following a clinically realistic intervention in terms of approach, intensity and duration.

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial

PubMed Central

Fernie, Gordon; Currie, James; Perrin, Jennifer S.; Stewart, Caroline A.; Anderson, Virginica; Bennett, Daniel M.; Hay, Steven; Reid, Ian C.

2017-01-01

Background Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs). Aims To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic. Method Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.) Results No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Conclusions Ketamine as an anaesthetic does not enhance the efficacy of ECT. PMID:28254962

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice. Methods/Design The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs. Discussion The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients. Trial Registration Netherlands Trial Register (NTR): NTR2666 PMID:22236534

Immunoglobulin for necrotising soft tissue infections (INSTINCT): protocol for a randomised trial.

PubMed

Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl; Perner, Anders

2016-07-01

Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may have beneficial effects. However, IVIG may also have adverse effects. With this trial we will estimate the effects of IVIG on a patient-reported outcome and other patient-centred outcomes in patients with NSTI. INSTINCT is a randomised, double-blinded, parallel-group, placebo-controlled trial with concealed allocation of patients with NSTI 1:1 to IVIG or an equal volume of 0.9% saline. Patients are recruited at Rigshospitalet, Denmark. The primary outcome is the physical component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey as assessed six months after randomisation. Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. This study will be the only completed trial testing IVIG for NSTI, thereby providing important data on a severely sick patient group. The trial is supported by CSL Behring in the form of trial medication and a € 92,182 grant for trial conduct, research, nurse salary and statistical analyses. The trial is registered with clinicaltrials.gov (NCT02111161). .

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers.

PubMed

Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

2013-10-01

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32.0% ± 47.3% versus 97.1% ± 7.0% (P < 0.001) after 4 weeks, whereas at 6 weeks wounds were reduced by -1.8% ± 70.3% versus 98.4% ± 5.8% (P < 0.001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0.001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Bimatoprost 0.03% preservative-free ophthalmic solution versus bimatoprost 0.03% ophthalmic solution (Lumigan) for glaucoma or ocular hypertension: a 12-week, randomised, double-masked trial

PubMed Central

Day, Douglas G; Walters, Thomas R; Schwartz, Gail F; Mundorf, Thomas K; Liu, Charlie; Schiffman, Rhett M; Bejanian, Marina

2013-01-01

Background/Aim To evaluate efficacy and safety of bimatoprost 0.03% preservative-free (PF) ophthalmic solution versus bimatoprost 0.03% (Lumigan) ophthalmic solution for glaucoma or ocular hypertension. Methods In this double-masked, parallel-group study, patients were randomised to bimatoprost PF or bimatoprost for 12 weeks. The primary analysis for non-inferiority was change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12. For equivalence, it was average eye IOP in the intent-to-treat population at each time point at weeks 2, 6 and 12. Results 597 patients were randomised (bimatoprost PF, n=302 and bimatoprost, n=295). The 95% CI upper limit for worse eye IOP change from baseline was <1.5 mm Hg at each week 12 time point, meeting prespecified non-inferiority criteria. The 95% CI upper limit for the treatment difference for average IOP was 0.69 mm Hg and the lower limit was −0.50 mm Hg at all follow-up time points (hours 0, 2 and 8 at weeks 2, 6 and 12), meeting equivalence criteria. Both treatments showed decreases in mean average eye IOP at all follow-up time points (p<0.001), were safe and well tolerated. Conclusions Bimatoprost PF is non-inferior and equivalent to bimatoprost in its ability to reduce IOP-lowering with a safety profile similar to bimatoprost. PMID:23743437

The efficacy and safety of extended-release methylphenidate following traumatic brain injury: a randomised controlled pilot study.

PubMed

Dymowski, Alicia R; Ponsford, Jennie L; Owens, Jacqueline A; Olver, John H; Ponsford, Michael; Willmott, Catherine

2017-06-01

To investigate the feasibility, safety and efficacy of extended-release methylphenidate in enhancing processing speed, complex attentional functioning and everyday attentional behaviour after traumatic brain injury. Seven week randomised, placebo-controlled, double-blind, parallel pilot study. Inpatient and outpatient Acquired Brain Injury Rehabilitation Program. Eleven individuals with reduced processing speed and/or attention deficits following complicated mild to severe traumatic brain injury. Participants were allocated using a blocked randomisation schedule to receive daily extended-release methylphenidate (Ritalin ® LA at a dose of 0.6 mg/kg) or placebo (lactose) in identical capsules. Tests of processing speed and complex attention, and ratings of everyday attentional behaviour were completed at baseline, week 7 (on-drug), week 8 (off-drug) and 9 months follow-up. Vital signs and side effects were monitored from baseline to week 8. Three percent ( n = 11) of individuals screened participated (mean post-traumatic amnesia duration = 63.80 days, SD = 45.15). Results were analysed for six and four individuals on methylphenidate and placebo, respectively. Groups did not differ on attentional test performance or relative/therapist ratings of everyday attentional behaviour. One methylphenidate participant withdrew due to difficulty sleeping. Methylphenidate was associated with trends towards increased blood pressure and reported anxiety. Methylphenidate was not associated with enhanced processing speed, attentional functioning or everyday attentional behaviour after traumatic brain injury. Alternative treatments for attention deficits after traumatic brain injury should be explored given the limited feasibility of methylphenidate in this population.

Tweeting links to Cochrane Schizophrenia Group reviews: a randomised controlled trial.

PubMed

Adams, C E; Jayaram, M; Bodart, A Y M; Sampson, S; Zhao, S; Montgomery, A A

2016-03-08

To assess the effects of using health social media on web activity. Individually randomised controlled parallel group superiority trial. Twitter and Weibo. 170 Cochrane Schizophrenia Group full reviews with an abstract and plain language summary web page. Three randomly ordered slightly different 140 character or less messages, each containing a short URL to the freely accessible summary page sent on specific times on one single day. This was compared with no messaging. The primary outcome was web page visits at 1 week. Secondary outcomes were other metrics of web activity at 1 week. 85 reviews were randomised to each of the intervention and control arms. Google Analytics allowed 100% follow-up within 1 week of completion. Intervention and control reviews received a total of 1162 and 449 visits, respectively (IRR 2.7, 95% CI 2.2 to 3.3). Fewer intervention reviews had single page only visits (16% vs 31%, OR 0.41, 0.19 to 0.88) and users spent more time viewing intervention reviews (geometric mean 76 vs 31 s, ratio 2.5, 1.3 to 4.6). Other secondary metrics of web activity all showed strong evidence in favour of the intervention. Tweeting in this limited area of healthcare increases 'product placement' of evidence with the potential for that to influence care. ISRCTN84658943. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial.

PubMed

Sumukadas, Deepa; Price, Rosemary; McMurdo, Marion E T; Rauchhaus, Petra; Struthers, Allan; McSwiggan, Stephen; Arnold, Graham; Abboud, Rami; Witham, Miles

2018-01-01

double-blind, parallel group, placebo-controlled randomised trial. we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). perindopril did not improve postural sway in older people at risk of falls. ISRCTN58995463. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.

Plasmonic Nanoholes in a Multi-Channel Microarray Format for Parallel Kinetic Assays and Differential Sensing

PubMed Central

Im, Hyungsoon; Lesuffleur, Antoine; Lindquist, Nathan C.; Oh, Sang-Hyun

2009-01-01

We present nanohole arrays in a gold film integrated with a 6-channel microfluidic chip for parallel measurements of molecular binding kinetics. Surface plasmon resonance effects in the nanohole arrays enable real-time label-free measurements of molecular binding events in each channel, while adjacent negative reference channels can record measurement artifacts such as bulk solution index changes, temperature variations, or changing light absorption in the liquid. Using this platform, streptavidin-biotin specific binding kinetics are measured at various concentrations with negative controls. A high-density microarray of 252 biosensing pixels is also demonstrated with a packing density of 106 sensing elements/cm2, which can potentially be coupled with a massively parallel array of microfluidic channels for protein microarray applications. PMID:19284776

Cortical and subcortical afferents to the nucleus reticularis tegmenti pontis and basal pontine nuclei in the macaque monkey.

PubMed

Giolli, R A; Gregory, K M; Suzuki, D A; Blanks, R H; Lui, F; Betelak, K F

2001-01-01

Anatomical findings are presented that identify cortical and subcortical sources of afferents to the nucleus reticularis tegmenti pontis (NRTP) and basal pontine nuclei. Projections from the middle temporal visual area (MT), medial superior temporal visual area (MST), lateral intraparietal area (LIP), and areas 7a and 7b to the basal pontine nuclei were studied using 3H-leucine autoradiography. The results complemented a parallel study of retrograde neuronal labeling attributable to injecting WGA-HRP into NRTP and neighboring pontine nuclei. Small 3H-leucine injections confined to MT, MST, LIP, area 7a, or area 7b, produced multiple patches of pontine terminal label distributed as follows: (1) An injection within MT produced terminal label limited to the dorsolateral and lateral pontine nuclei. (2) Injections restricted to MST or LIP showed patches of terminal label in the dorsal, dorsolateral, lateral, and peduncular pontine nuclei. (3) Area 7a targets the dorsal, dorsolateral, lateral, peduncular, and ventral pontine nuclei, whereas area 7b projects, additionally, to the dorsomedial and paramedian pontine nuclei. Notably, no projections were seen to NRTP from any of these cortical areas. In contrast, injections made by other investigators into cortical areas anterior to the central sulcus revealed cerebrocortical afferents to NRTP, in addition to nuclei of the basal pontine gray. With our pontine WGA-HRP injections, retrograde neuronal labeling was observed over a large extent of the frontal cortex continuing onto the medial surface which included the lining of the cingulate sulcus and cingulate gyrus. Significant subcortical sources for afferents to the NRTP and basal pontine nuclei were the zona incerta, ventral mesencephalic tegmentum, dorsomedial hypothalamic area, rostral interstitial nucleus of the medial longitudinal fasciculus, red nucleus, and subthalamic nucleus. The combined anterograde and retrograde labeling data indicated that visuo-motor cortico-pontine pathways arising from parietal cortices target only the basal pontine gray, whereas the NRTP, together with select pontine nuclei, is a recipient of afferents from frontal cortical areas. The present findings implicate the existence of parallel direct and indirect cortico-pontine pathways from frontal motor-related cortices to NRTP and neighboring pontine nuclei.

The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial.

PubMed

Berk, Michael; Dean, Olivia; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa S; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Allwang, Christine; Cobb, Heidi; Bush, Ashley I; Schapkaitz, Ian; Dodd, Seetal; Malhi, Gin S

2011-12-01

Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (p<0.001). Improvements in functioning and quality of life were similarly evident. These open label data demonstrate a robust decrement in depression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

Randomised, prospective, medico-economic nationwide French study of islet transplantation in patients with severely unstable type 1 diabetes: the STABILOT study protocol.

PubMed

Lablanche, Sandrine; David-Tchouda, Sandra; Margier, Jennifer; Schir, Edith; Wojtusciszyn, Anne; Borot, Sophie; Kessler, Laurence; Morelon, Emmanuel; Thivolet, Charles; Pattou, François; Vantyghem, Marie Christine; Berney, Thierry; Benhamou, Pierre-Yves

2017-02-20

Islet transplantation may be an appropriate treatment option for patients with severely unstable type 1 diabetes experiencing major glucose variability with severe hypoglycaemia despite intensive insulin therapy. Few data are available on the costs associated with islet transplantation in relation to its benefits. The STABILOT study proposes to assess the economic impact of islet transplantation in comparison with the current best medical treatment defined as sensor-augmented pump (SAP) therapy. The trial will adopt an open-label, randomised, multicentred design. The study will include 30 patients with severely unstable type 1 diabetes. Eligible participants will be 18-65 years old, with type 1 diabetes duration >5 years, a negative basal or stimulated C-peptide, and severe instability defined by persistent, recurrent and disabling severe hypoglycaemia, despite optimised medical treatment. Participants will be randomised into two groups: one group with immediate registration for islet transplantation, and one group with delayed registration for 1 year while patients receive SAP therapy. The primary endpoint will be the incremental cost-utility ratio at 1 year between islet transplantation and SAP therapy. Perspectives of both the French Health Insurance System and the hospitals will be retained. Ethical approval has been obtained at all sites. The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02854696). All participants will sign a free and informed consent form before randomisation. Results of the study will be communicated during national and international meetings in the field of diabetes and transplantation. A publication will be sought in journals usually read by physicians involved in diabetes care, transplantation and internal medicine. NCT02854696; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

VALFORTA: a randomised trial to validate the FORTA (Fit fOR The Aged) classification.

PubMed

Wehling, Martin; Burkhardt, Heinrich; Kuhn-Thiel, Alexandra; Pazan, Farhad; Throm, Christina; Weiss, Christel; Frohnhofen, Helmut

2016-03-01

to further validate the FORTA (Fit fOR The Aged) concept, a bicentric randomised, controlled trial was run in two geriatric clinics. patients (≥65 years, ≥3 drugs or ≥60 years, ≥6 drugs) with three relevant diseases and hospitalisation for ≥5 days were randomised. In the intervention, but not the control group, a FORTA team instructed ward physicians on FORTA. FORTA is the first positive/negative listing approach labelling medications used to treat chronic illnesses in older patients from A (indispensable), B (beneficial), C (questionable) to D (avoid). The primary end point was the FORTA score: sum of medication errors classified as over-, under- and mistreatment. Consecutive patients were randomised to the intervention and control ward; outcome assessment was blinded. four hundred and nine patients (age 81.5 years, 64% female, hospitalisation 17.4 days) were included. The primary end point was significantly (P < 0.0001) more reduced in the intervention versus control groups (2.7 ± 2.25 versus 1 ± 1.8, mean ± SD, intergroup comparison of admission/discharge differences). Over- and under-treatment scores and use of A (increase) and D (decrease) drugs were significantly improved (P < 0.01). The total number of adverse drug reactions (ADRs) was significantly reduced by FORTA (P < 0.05, number needed to treat is 5). Activities of daily living and renal failure improved significantly (P < 0.05). Blood pressure remained constant in the intervention, but decreased significantly in the control group. applying FORTA to hospitalised geriatric patients leads to improvement of medication quality and may improve secondary clinical end points (e.g. ADRs). The concept is amenable to successful communication and implementation. Registration (DRKS-ID): DRKS00000531. DFG-German Research Foundation (WE 1184/15-1). © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thrombus aspiration in non-ST-elevation myocardial infarction - 12-month clinical outcome of the randomised TATORT-NSTEMI trial.

PubMed

Meyer-Saraei, Roza; de Waha, Suzanne; Eitel, Ingo; Desch, Steffen; Scheller, Bruno; Böhm, Michael; Lauer, Bernward; Gawaz, Meinrad; Geisler, Tobias; Gunkel, Oliver; Bruch, Leonhard; Klein, Norbert; Pfeiffer, Dietrich; Schuler, Gerhard; Zeymer, Uwe; Thiele, Holger

2017-02-01

In the randomised TATORT-NSTEMI trial routine thrombus aspiration in comparison with standard percutaneous coronary intervention (PCI) did not reduce the primary endpoint of microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with non-ST-elevation myocardial infarction (NSTEMI). So far, no data on long-term outcome of head-to-head comparisons between both treatment strategies in NSTEMI patients have been reported. The prospective, controlled, multicentre, randomised, open-label TATORT-NSTEMI trial assigned patients with NSTEMI and thrombus-containing lesions to aspiration thrombectomy plus PCI ( n=221) or standard PCI only ( n=219). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events defined as the composite of death, myocardial reinfarction, target vessel revascularisation, and new congestive heart failure at 12-month follow-up. In addition, functional outcome and quality of life were assessed. At one year, major adverse cardiac events occurred in 19 patients in the thrombectomy arm and 29 patients in the standard PCI group (8.7% vs. 13.4%, relative risk 0.63, 95% confidence interval 0.35-1.12, p=0.11). The individual components of the combined endpoint such as death ( p=0.20), myocardial reinfarction ( p=0.73), target vessel revascularisation ( p=0.42), and congestive heart failure ( p=0.18) were similar in both groups. Functional outcome and quality of life did not differ significantly between both groups (Canadian Cardiovascular Society class: p=0.68, New York Heart Association class: p=0.70 and EuroQol5D score: p=0.96). Post-hoc analyses revealed consistent results with regard to the occurrence of major adverse cardiac events across a wide range of subgroups (all p>0.05). In this first randomised trial on thrombectomy in NSTEMI patients, routine thrombus aspiration before PCI did not improve clinical outcome at 12-month follow-up.

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.

PubMed

Crabb, Simon; Danson, Sarah J; Catto, James W F; McDowell, Cathy; Lowder, James N; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Hathorn, David; Whitehead, Amy; Kalevras, Mihalis; Huddart, Robert; Griffiths, Gareth

2018-04-03

Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC. EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial.

PubMed

Münch, Andreas; Bohr, Johan; Miehlke, Stephan; Benoni, Cecilia; Olesen, Martin; Öst, Åke; Strandberg, Lars; Hellström, Per M; Hertervig, Erik; Armerding, Peter; Stehlik, Jiri; Lindberg, Greger; Björk, Jan; Lapidus, Annika; Löfberg, Robert; Bonderup, Ole; Avnström, Sören; Rössle, Martin; Dilger, Karin; Mueller, Ralph; Greinwald, Roland; Tysk, Curt; Ström, Magnus

2016-01-01

This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation. http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial.

PubMed

Gauthier, Serge; Feldman, Howard H; Schneider, Lon S; Wilcock, Gordon K; Frisoni, Giovanni B; Hardlund, Jiri H; Moebius, Hans J; Bentham, Peter; Kook, Karin A; Wischik, Damon J; Schelter, Bjoern O; Davis, Charles S; Staff, Roger T; Bracoud, Luc; Shamsi, Kohkan; Storey, John M D; Harrington, Charles R; Wischik, Claude M

2016-12-10

Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease. We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31-7·34]: 75 mg LMTM twice a day [n=257] -0·02, -1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] -0·43, -2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [-8·22, 95% CI -9·63 to -6·82]: 75 mg LMTM twice a day -0·93, -3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day -0·34, -2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon. TauRx Therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial

PubMed Central

Gauthier, Serge; Feldman, Howard H; Schneider, Lon S; Wilcock, Gordon K; Frisoni, Giovanni B; Hardlund, Jiri H; Moebius, Hans J; Bentham, Peter; Kook, Karin A; Wischik, Damon J; Schelter, Bjoern O; Davis, Charles S; Staff, Roger T; Bracoud, Luc; Shamsi, Kohkan; Storey, John M D; Harrington, Charles R; Wischik, Claude M

2016-01-01

Summary Background Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer’s disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer’s disease. Methods We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer’s disease. Patients concomitantly using other medicines for Alzheimer’s disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer’s disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and the Alzheimer’s Disease Co-operative Study–Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Findings Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31–7·34]: 75 mg LMTM twice a day [n=257] –0·02, –1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] –0·43, –2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [–8·22, 95% CI –9·63 to –6·82]: 75 mg LMTM twice a day –0·93, –3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day –0·34, –2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. Interpretation The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer’s disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer’s disease will be reported soon. Funding TauRx Therapeutics. PMID:27863809

Peptide-membrane Interactions by Spin-labeling EPR

PubMed Central

Smirnova, Tatyana I.; Smirnov, Alex I.

2016-01-01

Site-directed spin labeling (SDSL) in combination with Electron Paramagnetic Resonance (EPR) spectroscopy is a well-established method that has recently grown in popularity as an experimental technique, with multiple applications in protein and peptide science. The growth is driven by development of labeling strategies, as well as by considerable technical advances in the field, that are paralleled by an increased availability of EPR instrumentation. While the method requires an introduction of a paramagnetic probe at a well-defined position in a peptide sequence, it has been shown to be minimally destructive to the peptide structure and energetics of the peptide-membrane interactions. In this chapter, we describe basic approaches for using SDSL EPR spectroscopy to study interactions between small peptides and biological membranes or membrane mimetic systems. We focus on experimental approaches to quantify peptide-membrane binding, topology of bound peptides, and characterize peptide aggregation. Sample preparation protocols including spin-labeling methods and preparation of membrane mimetic systems are also described. PMID:26477253

Nucleic Acid Detection Methods

DOEpatents

Smith, Cassandra L.; Yaar, Ron; Szafranski, Przemyslaw; Cantor, Charles R.

1998-05-19

The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.

The efficacy of a brief intervention in reducing hazardous drinking in working age men in Russia: the HIM (Health for Izhevsk men) individually randomised parallel group exploratory trial

PubMed Central

2011-01-01

Background Russia has particularly low life expectancy for an industrialised country, with mortality at working ages having fluctuated dramatically over the past few decades, particularly among men. Alcohol has been identified as the most likely cause of these temporal variations. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. Very few studies to evaluate the efficacy of brief interventions in Russia have been conducted. Motivational Interviewing (MI) is a person-centred counselling style which can be adapted to brief interventions in which help is offered in thinking through behaviour in the context of values and goals, to decide whether change is needed, and if so, how it may best be achieved. Methods This paper reports on an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous and harmful drinking at 3 months. Participants were drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous and harmful drinking in the past year. All participants underwent a health check, with MI subsequently delivered to those in the intervention arm. Signed consent was obtained from those in the intervention arm only at this point. Both groups were then invited for 3 and 12 month follow ups. The control group did not receive any additional intervention. Results 441 men were randomised. Of these 61 did not have a health check leaving 190 in each trial arm. Follow up at 3 months was high (97% of those having a health check), and very similar in the two trial arms (183 in the intervention and 187 in the control). No significant differences were detected between the randomised groups in either the primary or the secondary outcomes at three months in the intention to treat analyses. The unadjusted odds ratio (95% CI) for the effect of MI on hazardous and harmful drinking was 0.77 (0.51, 1.16). An adjusted odds ratio of 0.52 (0.28, 0.94) was obtained in the pre-specified per protocol analysis. Conclusions This trial demonstrates that it is possible to engage Russian men who drink hazardously in a brief intervention aimed at reducing alcohol related harm. However the results with respect to the efficacy are equivocal and further, larger-scale trials are warranted. Trial Registration ISRCTN: ISRCTN82405938 PMID:22053775

Shrinkage of X cells in the lateral geniculate nucleus after monocular deprivation revealed by FoxP2 labeling.

PubMed

Duffy, Kevin R; Holman, Kaitlyn D; Mitchell, Donald E

2014-05-01

The parallel processing of visual features by distinct neuron populations is a central characteristic of the mammalian visual system. In the A laminae of the cat dorsal lateral geniculate nucleus (dLGN), parallel processing streams originate from two principal neuron types, called X and Y cells. Disruption of visual experience early in life by monocular deprivation has been shown to alter the structure and function of Y cells, but the extent to which deprivation influences X cells remains less clear. A transcription factor, FoxP2, has recently been shown to selectively label X cells in the ferret dLGN and thus provides an opportunity to examine whether monocular deprivation alters the soma size of X cells. In this study, FoxP2 labeling was examined in the dLGN of normal and monocularly deprived cats. The characteristics of neurons labeled for FoxP2 were consistent with FoxP2 being a marker for X cells in the cat dLGN. Monocular deprivation for either a short (7 days) or long (7 weeks) duration did not alter the density of FoxP2-positive neurons between nondeprived and deprived dLGN layers. However, for each deprived animal examined, measurement of the cross-sectional area of FoxP2-positive neurons (X cells) revealed that within deprived layers, X cells were smaller by approximately 20% after 7 days of deprivation, and by approximately 28% after 7 weeks of deprivation. The observed alteration to the cross-sectional area of X cells indicates that perturbation of this major pathway contributes to the functional impairments that develop from monocular deprivation.

Robust Statistical Fusion of Image Labels

PubMed Central

Landman, Bennett A.; Asman, Andrew J.; Scoggins, Andrew G.; Bogovic, John A.; Xing, Fangxu; Prince, Jerry L.

2011-01-01

Image labeling and parcellation (i.e. assigning structure to a collection of voxels) are critical tasks for the assessment of volumetric and morphometric features in medical imaging data. The process of image labeling is inherently error prone as images are corrupted by noise and artifacts. Even expert interpretations are subject to subjectivity and the precision of the individual raters. Hence, all labels must be considered imperfect with some degree of inherent variability. One may seek multiple independent assessments to both reduce this variability and quantify the degree of uncertainty. Existing techniques have exploited maximum a posteriori statistics to combine data from multiple raters and simultaneously estimate rater reliabilities. Although quite successful, wide-scale application has been hampered by unstable estimation with practical datasets, for example, with label sets with small or thin objects to be labeled or with partial or limited datasets. As well, these approaches have required each rater to generate a complete dataset, which is often impossible given both human foibles and the typical turnover rate of raters in a research or clinical environment. Herein, we propose a robust approach to improve estimation performance with small anatomical structures, allow for missing data, account for repeated label sets, and utilize training/catch trial data. With this approach, numerous raters can label small, overlapping portions of a large dataset, and rater heterogeneity can be robustly controlled while simultaneously estimating a single, reliable label set and characterizing uncertainty. The proposed approach enables many individuals to collaborate in the construction of large datasets for labeling tasks (e.g., human parallel processing) and reduces the otherwise detrimental impact of rater unavailability. PMID:22010145

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

Effectiveness of a standardised exercise programme for recurrent neck and low back pain: a multicentre, randomised, two-arm, parallel group trial across 34 fitness clubs in Finland.

PubMed

Suni, Jaana H; Rinne, Marjo; Tokola, Kari; Mänttäri, Ari; Vasankari, Tommi

2017-01-01

Neck and low back pain (LBP) are common in office workers. Exercise trials to reduce neck and LBP conducted in sport sector are lacking. We investigated the effectiveness of the standardised Fustra20Neck&Back exercise program for reducing pain and increasing fitness in office workers with recurrent non-specific neck and/or LBP. Volunteers were recruited through newspaper and Facebook. The design is a multi-centre randomised, two-arm, parallel group trial across 34 fitness clubs in Finland. Eligibility was determined by structured telephone interview. Instructors were specially educated professionals. Neuromuscular exercise was individually guided twice weekly for 10 weeks. Webropol survey, and objective measurements of fitness, physical activity, and sedentary behavior were conducted at baseline, and at 3 and 12 months. Mean differences between study groups (Exercise vs Control) were analysed using a general linear mixed model according to the intention-to-treat principle. At least moderate intensity pain (≥40 mm) in both the neck and back was detected in 44% of participants at baseline. Exercise compliance was excellent: 92% participated 15-20 times out of 20 possible. Intensity and frequency of neck pain, and strain in neck/shoulders decreased significantly in the Exercise group compared with the Control group. No differences in LBP and strain were detected. Neck/shoulder and trunk flexibility improved, as did quality of life in terms of pain and physical functioning. The Fustra20Neck&Back exercise program was effective for reducing neck/shoulder pain and strain, but not LBP. Evidence-based exercise programs of sports clubs have potential to prevent persistent, disabling musculoskeletal problems.

Examining the Conceptualization of Instructional Technology in Turkey

ERIC Educational Resources Information Center

Gedik, Nuray

2017-01-01

Instructional Technology is a field having approximately a century old past. From its initial conceptualization to date, it has been in question in terms of its label, definition, and scope. Parallel to international interest, Turkey has embraced IT as a field of study and practice. This qualitative study aims to investigate the existing…

GPU surface extraction using the closest point embedding

NASA Astrophysics Data System (ADS)

Kim, Mark; Hansen, Charles

2015-01-01

Isosurface extraction is a fundamental technique used for both surface reconstruction and mesh generation. One method to extract well-formed isosurfaces is a particle system; unfortunately, particle systems can be slow. In this paper, we introduce an enhanced parallel particle system that uses the closest point embedding as the surface representation to speedup the particle system for isosurface extraction. The closest point embedding is used in the Closest Point Method (CPM), a technique that uses a standard three dimensional numerical PDE solver on two dimensional embedded surfaces. To fully take advantage of the closest point embedding, it is coupled with a Barnes-Hut tree code on the GPU. This new technique produces well-formed, conformal unstructured triangular and tetrahedral meshes from labeled multi-material volume datasets. Further, this new parallel implementation of the particle system is faster than any known methods for conformal multi-material mesh extraction. The resulting speed-ups gained in this implementation can reduce the time from labeled data to mesh from hours to minutes and benefits users, such as bioengineers, who employ triangular and tetrahedral meshes

Microfluidic flow fractionation device for label-free isolation of circulating tumor cells (CTCs) from breast cancer patients.

PubMed

Hyun, Kyung-A; Kwon, Kiho; Han, Hyunju; Kim, Seung-Il; Jung, Hyo-Il

2013-02-15

Circulating tumor cells (CTCs) are dissociated from primary tumor and circulate in peripheral blood. They are regarded as the genesis of metastasis. Isolation and enumeration of CTCs serve as valuable tools for cancer prognosis and diagnosis. However, the rarity and heterogeneity of CTCs in blood makes it difficult to separate intact CTCs without loss. In this paper, we introduce a parallel multi-orifice flow fractionation (p-MOFF) device in which a series of contraction/expansion microchannels are placed parallel on a chip forming four identical channels. CTCs were continuously isolated from the whole blood of breast cancer patients by hydrodynamic forces and cell size differences. Blood samples from 24 breast cancer patients were analyzed (half were from metastatic breast cancer patients and the rest were from adjuvant breast cancer patients). The number of isolated CTCs varied from 0 to 21 in 7.5 ml of blood. Because our devices do not require any labeling processes (e.g., EpCAM antibody), heterogeneous CTCs can be isolated regardless of EpCAM expression. Copyright © 2012 Elsevier B.V. All rights reserved.

Therapeutic effect of intranasal evaporative cooling in patients with migraine: a pilot study.

PubMed

Vanderpol, Jitka; Bishop, Barbara; Matharu, Manjit; Glencorse, Mark

2015-01-26

Cryotherapy is the most common non-pharmacological pain-relieving method. The aim of this pilot study was to ascertain whether intranasal evaporative cooling may be an effective intervention in an acute migraine attack. Studies have previously demonstrated effectiveness of a variety of cryotherapy approaches. Intranasal evaporative cooling due to vascular anatomy, allows the transfer of venous blood from nasal and paranasal mucous membranes to the dura mater, thereby providing an excellent anatomical basis for the cooling processes. We conducted a prospective, open-label, observational, pilot study. Twenty-eight patients who satisfied the International Classification of Headache Disorders (ICHD 2) diagnostic criteria for migraine were recruited. A total of 20 treatments were administered in 15 patients. All patients provided pain severity scores and migraine-associated symptoms severity scores (based on a 0-10 visual analogue scale, [VAS]). Out of the 20 treatments, intranasal evaporative cooling rendered patients' pain and symptoms free immediately after treatment, in 8 of the treatments (40%), a further 10 treatments (50%) resulted in partial pain relief (headache reduced from severe or moderate to mild) and partial symptoms relief. At 2 hours, 9 treatments (45%) provided full pain and symptoms relief, with a further 9 treatments (45%) resulting in partial pain and symptoms relief. At 24 hours, 10 treatments (50%) resulted in patients reporting pain and symptom freedom and 3 (15%) provided partial pain relief. In summary 13 patients (87%) had benefit from the treatment within 2 hours that was sustained at 24 hours. Intranasal evaporative cooling gave considerable benefit to patients with migraine, improving headache severity and migraine-associated symptoms. A further randomised, placebo controlled, double blinded, parallel clinical trial is required to further investigate the potential of this application. Clinicaltrials.gov registered trial, ClinicalTrials.gov Identifier: NCT01898455.

An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers.

PubMed

Morelli, G; Chen, H; Rossiter, G; Rege, B; Lu, Y

2011-04-01

Novel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients. To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole-ER formulations vs. esomeprazole 40 mg and rabeprazole delayed-release (DR) 20 mg. Helicobacter pylori-negative healthy subjects were randomised to receive one of eight treatments once daily for 5 days. Twenty-four-hour intragastric pH was monitored on days -1, 1 and 5. Rabeprazole plasma concentrations were measured on day 5. A total of 248 subjects (N=31/group) were enrolled in the study. On day 5, rabeprazole-ER groups provided mean durations of 18.5-20.2 h (77.0-84.1% of 24-h) with intragastric pH >4.0 vs. esomeprazole 40 mg (15.9 h/66.1% of 24-h) and rabeprazole-DR 20 mg (15.2 h/63.2% of 24-h). A similar increase was observed on day 1. While percentage of daytime (8 am-10 pm) with intragastric pH >4.0 on day 5 was overall similar across the groups, percentage of night-time (10 pm-8 am) with intragastric pH >4.0 was higher with the rabeprazole-ER groups (57.0-72.4%) vs. esomeprazole 40 mg (32.8%) and rabeprazole-DR 20 mg (34.0%). Rabeprazole-ER once daily for 5 days demonstrated a significantly longer duration of gastric acid suppression in 24 h vs. esomeprazole 40 mg and rabeprazole-DR 20 mg. The increase in acid suppression was predominantly due to prolonged acid suppression during the night-time; this was supported by the extended-release pharmacokinetic characteristics. © 2011 Blackwell Publishing Ltd.

6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial.

PubMed

Samandari, Taraz; Agizew, Tefera B; Nyirenda, Samba; Tedla, Zegabriel; Sibanda, Thabisa; Shang, Nong; Mosimaneotsile, Barudi; Motsamai, Oaitse I; Bozeman, Lorna; Davis, Margarett K; Talbot, Elizabeth A; Moeti, Themba L; Moffat, Howard J; Kilmarx, Peter H; Castro, Kenneth G; Wells, Charles D

2011-05-07

In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per μL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3·4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2·0%) in 1006 allocated to the continued isoniazid group (incidence 1·26% per year vs 0·72%; hazard ratio 0·57, 95% CI 0·33-0·99, p=0·047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0·26, 0·09-0·80, p=0·02), whereas participants who were tuberculin skin test-negative received no significant benefit (0·75, 0·38-1·46, p=0·40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0·50, 95% CI 0·26-0·97). Severe adverse events and death were much the same in the control and continued isoniazid groups. In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. US Centers for Disease Control and Prevention and US Agency for International Development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Design and rationale for a randomised comparison of everolimus-eluting stents and coronary artery bypass graft surgery in selected patients with left main coronary artery disease: the EXCEL trial.

PubMed

Kappetein, Arie Pieter; Serruys, Patrick W; Sabik, Joseph F; Leon, Martin B; Taggart, David P; Morice, Marie-Claude; Gersh, Bernard J; Pocock, Stuart J; Cohen, David J; Wallentin, Lars; Ben-Yehuda, Ori; van Es, Gerrit-Anne; Simonton, Charles A; Stone, Gregg W

2016-09-18

Coronary artery bypass graft (CABG) surgery is the standard of care for revascularisation of patients with left main coronary artery disease (LMCAD). Recent studies have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may provide comparable outcomes in selected patients with LMCAD without extensive CAD. We therefore designed a trial to investigate whether PCI with XIENCE cobalt-chromium everolimus-eluting stents (CoCr-EES) would result in non-inferior or superior clinical outcomes to CABG in selected patients with LMCAD. The Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is a prospective, open-label, multicentre, international study of 1,900 randomised subjects. Patients with significant LMCAD with a SYNTAX score ≤32 and local Heart Team consensus that the subject is appropriate for revascularisation by both PCI and CABG are consented and randomised 1:1 to undergo PCI using CoCr-EES or CABG. All patients undergo follow-up for five years. The primary endpoint is the three-year composite rate of death, stroke or myocardial infarction, assessed at a median follow-up of at least three years (with at least two-year follow-up in all patients), powered for sequential non-inferiority and superiority testing. The EXCEL study will define the contemporary roles of CABG and PCI using XIENCE CoCr-EES in patients with LMCAD disease with low and intermediate SYNTAX scores.

Erythrocytapheresis compared with whole blood phlebotomy for the treatment of hereditary haemochromatosis

PubMed Central

Sundic, Tatjana; Hervig, Tor; Hannisdal, Signe; Assmus, Jörg; Ulvik, Rune J.; Olaussen, Richard W.; Berentsen, Sigbjørn

2014-01-01

Background Hereditary haemochromatosis may result in severe organ damage which can be prevented by therapy. We studied the possible advantages and disadvantages of erythrocytapheresis as compared with phlebotomy in patients with hereditary haemochromatosis. Materials and methods In a prospective, randomised, open-label study, patients with hereditary haemochromatosis were randomised to bi-weekly apheresis or weekly whole blood phlebotomy. Primary end-points were decrease in ferritin levels and transferrin saturation. Secondary endpoints were decrease in haemoglobin levels, discomfort during the therapeutic procedure, costs and technicians’ working time. Results Sixty-two patients were included. Thirty patients were randomised to apheresis and 32 to whole blood phlebotomy. Initially, ferritin levels declined more rapidly in the apheresis group, and the difference became statistically highly significant at 11 weeks; however, time to normalisation of ferritin level was equal in the two groups. We observed no significant differences in decline of transferrin saturation, haemoglobin levels or discomfort. The mean cumulative technician time consumption until the ferritin level reached 50 μg/L was longer in the apheresis group, but the difference was not statistically significant. The cumulative costs for materials until achievement of the desired ferritin levels were three-fold higher in the apheresis group. Conclusion Treatment of hereditary haemochromatosis with erythrocytapheresis instead of whole blood phlebotomy results in a more rapid initial decline in ferritin levels and a reduced number of procedures per patient, but not in earlier achievement of target ferritin level. The frequency of discomfort was equally low with the two methods. The costs and, probably, technician time consumption were higher in the apheresis group. PMID:24333062

Microfluidic integration of parallel solid-phase liquid chromatography.

PubMed

Huft, Jens; Haynes, Charles A; Hansen, Carl L

2013-03-05

We report the development of a fully integrated microfluidic chromatography system based on a recently developed column geometry that allows for robust packing of high-performance separation columns in poly(dimethylsiloxane) microfluidic devices having integrated valves made by multilayer soft lithography (MSL). The combination of parallel high-performance separation columns and on-chip plumbing was used to achieve a fully integrated system for on-chip chromatography, including all steps of automated sample loading, programmable gradient generation, separation, fluorescent detection, and sample recovery. We demonstrate this system in the separation of fluorescently labeled DNA and parallel purification of reverse transcription polymerase chain reaction (RT-PCR) amplified variable regions of mouse immunoglobulin genes using a strong anion exchange (AEX) resin. Parallel sample recovery in an immiscible oil stream offers the advantage of low sample dilution and high recovery rates. The ability to perform nucleic acid size selection and recovery on subnanogram samples of DNA holds promise for on-chip genomics applications including sequencing library preparation, cloning, and sample fractionation for diagnostics.

Parallel and serial grouping of image elements in visual perception.

PubMed

Houtkamp, Roos; Roelfsema, Pieter R

2010-12-01

The visual system groups image elements that belong to an object and segregates them from other objects and the background. Important cues for this grouping process are the Gestalt criteria, and most theories propose that these are applied in parallel across the visual scene. Here, we find that Gestalt grouping can indeed occur in parallel in some situations, but we demonstrate that there are also situations where Gestalt grouping becomes serial. We observe substantial time delays when image elements have to be grouped indirectly through a chain of local groupings. We call this chaining process incremental grouping and demonstrate that it can occur for only a single object at a time. We suggest that incremental grouping requires the gradual spread of object-based attention so that eventually all the object's parts become grouped explicitly by an attentional labeling process. Our findings inspire a new incremental grouping theory that relates the parallel, local grouping process to feedforward processing and the serial, incremental grouping process to recurrent processing in the visual cortex.

Solving Partial Differential Equations in a data-driven multiprocessor environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaudiot, J.L.; Lin, C.M.; Hosseiniyar, M.

1988-12-31

Partial differential equations can be found in a host of engineering and scientific problems. The emergence of new parallel architectures has spurred research in the definition of parallel PDE solvers. Concurrently, highly programmable systems such as data-how architectures have been proposed for the exploitation of large scale parallelism. The implementation of some Partial Differential Equation solvers (such as the Jacobi method) on a tagged token data-flow graph is demonstrated here. Asynchronous methods (chaotic relaxation) are studied and new scheduling approaches (the Token No-Labeling scheme) are introduced in order to support the implementation of the asychronous methods in a data-driven environment.more » New high-level data-flow language program constructs are introduced in order to handle chaotic operations. Finally, the performance of the program graphs is demonstrated by a deterministic simulation of a message passing data-flow multiprocessor. An analysis of the overhead in the data-flow graphs is undertaken to demonstrate the limits of parallel operations in dataflow PDE program graphs.« less

A pilot randomised controlled trial to assess the utility of an e-learning package that trains users in adverse drug reaction causality.

PubMed

Conroy, Elizabeth J; Kirkham, Jamie J; Bellis, Jennifer R; Peak, Matthew; Smyth, Rosalind L; Williamson, Paula R; Pirmohamed, Munir

2015-12-01

Causality assessment of adverse drug reactions (ADRs) by healthcare professionals is often informal which can lead to inconsistencies in practice. The Liverpool Causality Assessment Tool (LCAT) offers a systematic approach. An interactive, web-based, e-learning package, the Liverpool ADR Causality Assessment e-learning Package (LACAeP), was designed to improve causality assessment using the LCAT. This study aimed to (1) get feedback on usability and usefulness on the LACAeP, identify areas for improvement and development, and generate data on effect size to inform a larger scale study; and (2) test the usability and usefulness of the LCAT. A pilot, single-blind, parallel-group, randomised controlled trial hosted by the University of Liverpool was undertaken. Participants were paediatric medical trainees at specialty training level 1+ within the Mersey and North-West England Deaneries. Participants were randomised (1 : 1) access to the LACAeP or no training. The primary efficacy outcome was score by correct classification, predefined by a multidisciplinary panel of experts. Following participation, feedback on both the LCAT and the LACAeP was obtained, via a built in survey, from participants. Of 57 randomised, 35 completed the study. Feedback was mainly positive although areas for improvement were identified. Seventy-four per cent of participants found the LCAT easy to use and 78% found the LACAeP training useful. Sixty-one per cent would be unlikely to recommend the training. Scores ranged from 4 to 13 out of 20. The LACAeP increased scores by 1.3, but this was not significant. Improving the LACAeP before testing it in an appropriately powered trial, informed by the differences observed, is required. Rigorous evaluation will enable a quality resource that will be of value in healthcare professional training. © 2015 The Authors. International Journal of Pharmacy Practice published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.

Impact of pelvic floor muscle training on sexual function of women with urinary incontinence and a comparison of electrical stimulation versus standard treatment (IPSU trial): a randomised controlled trial.

PubMed

Jha, Swati; Walters, Stephen J; Bortolami, Oscar; Dixon, Simon; Alshreef, Abualbishr

2018-03-01

To evaluate the clinical and cost-effectiveness of electric stimulation plus standard pelvic floor muscle training compared to standard pelvic floor muscle training alone in women with urinary incontinence and sexual dysfunction. Single centre two arm parallel group randomised controlled trial conducted in a Teaching hospital in England. Participants were women presenting with urinary incontinence and sexual dysfunction. The interventions compared were electric stimulation versus standard pelvic floor muscle training. included Prolapse and Incontinence Sexual function Questionnaire (PISQ) physical function dimension at post-treatment (primary); other dimensions of PISQ, SF-36; EQ-5D, EPAQ, resource use, adverse events and cost-effectiveness (secondary outcomes). 114 women were randomised (Intervention n=57; Control group n=57). 64/114 (56%). had valid primary outcome data at follow-up (Intervention 30; Control 34). The mean PISQ-PF dimension scores at follow-up were 33.1 (SD 5.5) and 32.3 (SD 5.2) for the Intervention and Control groups respectively; with the Control group having a higher (better) score. After adjusting for baseline score, BMI, menopausal status, time from randomisation and baseline oxford scale score the mean difference was -1.0 (95% CI: -4.0 to 1.9; P=0.474). There was no differences between the groups in any of the secondary outcomes at follow-up. Within this study, the use of electrical stimulation was cost-effective with very small incremental costs and quality adjusted life years (QALYs). In women presenting with urinary incontinence in conjunction with sexual dysfunction, physiotherapy is beneficial to improve overall sexual function. However no specific form of physiotherapy is beneficial over another. Trial registration ISRCTN09586238. Copyright © 2017 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01).

PubMed

Pagès, Pierre-Benoit; Abou Hanna, Halim; Bertaux, Anne-Claire; Serge Aho, Ludwig Serge; Magdaleinat, Pierre; Baste, Jean-Marc; Filaire, Marc; de Latour, Richard; Assouad, Jalal; Tronc, François; Jayle, Christophe; Mouroux, Jérome; Thomas, Pascal-Alexandre; Falcoz, Pierre-Emmanuel; Marty-Ané, Charles-Henri; Bernard, Alain

2017-06-15

In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. NCT02502318. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy

PubMed Central

Choe, Jung-Yoon; Prodanovic, Nenad; Niebrzydowski, Jaroslaw; Staykov, Ivan; Dokoupilova, Eva; Baranauskaite, Asta; Yatsyshyn, Roman; Mekic, Mevludin; Porawska, Wieskawa; Ciferska, Hana; Jedrychowicz-Rosiak, Krystyna; Zielinska, Agnieszka; Choi, Jasmine; Rho, Young Hee; Smolen, Josef S

2017-01-01

Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. Trial registration number NCT01936181. PMID:26318384

The NEtherlands Cervical Kinematics (NECK) trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study.

PubMed

Arts, Mark P; Brand, Ronald; van den Akker, Elske; Koes, Bart W; Peul, Wilco C

2010-06-16

Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prosthesis is necessary and cost-effective will be determined by this trial. Netherlands Trial Register NTR1289.

Comparison of outcome measures and complication rates following three different approaches for primary total hip arthroplasty: a pragmatic randomised controlled trial.

PubMed

Talia, Adrian J; Coetzee, Cassandra; Tirosh, Oren; Tran, Phong

2018-01-08

Total hip arthroplasty is one of the most commonly performed surgical procedures worldwide. There are a number of surgical approaches for total hip arthroplasty and no high-level evidence supporting one approach over the other. Each approach has its unique benefits and drawbacks. This trial aims to directly compare the three most common surgical approaches for total hip arthroplasty. This is a single-centre study conducted at Western Health, Melbourne, Australia; a large metropolitan centre. It is a pragmatic, parallel three-arm, randomised controlled trial. Sample size will be 243 participants (81 in each group). Randomisation will be secure, web-based and managed by an independent statistician. Patients and research team will be blinded pre-operatively, but not post-operatively. Intervention will be either direct anterior, lateral or posterior approach for total hip arthroplasty, and the three arms will be directly compared. Participants will be aged over 18 years, able to provide informed consent and recruited from our outpatients. Patients who are having revision surgery or have indications for hip replacement other than osteoarthritis (i.e., fracture, malignancy, development dysplasia) will be excluded from the trial. The Oxford Hip Score will be determined for patients pre-operatively and 6 weeks, 6, 12 and 24 months post-operatively. The Oxford Hip Score at 24 months will be the primary outcome measure. Secondary outcome measures will be dislocation, infection, intraoperative and peri-prosthetic fracture rate, length of hospital stay and pain level, reported using a visual analogue scale. Many studies have evaluated approaches for total hip arthroplasty and arthroplasty registries worldwide are now collecting this data. However no study to date has compared these three common approaches directly in a randomised fashion. No trial has used patient-reported outcome measures to evaluate success. This pragmatic study aims to identify differences in patient perception of total hip arthroplasty depending on surgical approach. Australian New Zealand Clinical Trials Registry, ACTRN12617000272392 . Registered on 22 February 2017.

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

Systematic review and meta-analysis of randomised controlled trials on the effects of potassium supplements on serum potassium and creatinine.

PubMed

Cappuccio, Francesco P; Buchanan, Laura A; Ji, Chen; Siani, Alfonso; Miller, Michelle A

2016-08-26

High potassium intake could prevent stroke, but supplementation is considered hazardous. We assessed the effect of oral potassium supplementation on serum or plasma potassium levels and renal function. We updated a systematic review of the effects of potassium supplementation in randomised clinical trials carried out worldwide, published in 2013, extending it to July 2015. We followed the PRISMA guidelines. Any individual taking part in a potassium supplementation randomised clinical trial. Studies included met the following criteria: randomised clinical trials, potassium supplement given and circulating potassium levels reported. Oral potassium supplementation. Serum or plasma potassium and serum or plasma creatinine. A total of 20 trials (21 independent groups) were included (1216 participants from 12 different countries). All but 2 were controlled (placebo n=16, control n=2). Of these trials, 15 were crossover, 4 had a parallel group and 1 was sequential. The duration of supplementation varied from 2 to 24 weeks and the amount of potassium given from 22 to 140 mmol/day. In the pooled analysis, potassium supplementation caused a small but significant increase in circulating potassium levels (weighted mean difference (WMD) 0.14 mmol/L, 95% CI 0.09 to 0.19, p<1×10(-5)), not associated with dose or duration of treatment. The average increase in urinary potassium excretion was 45.75 mmol/24 hours, 95% CI 38.81 to 53.69, p<1×10(-5). Potassium supplementation did not cause any change in circulating creatinine levels (WMD 0.30 µmol/L, 95% CI -1.19 to 1.78, p=0.70). In short-term studies of relatively healthy persons, a moderate oral potassium supplement resulted in a small increase in circulating potassium levels and no change in renal function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Behavioural activation versus mindfulness-based guided self-help treatment administered through a smartphone application: a randomised controlled trial.

PubMed

Ly, Kien Hoa; Trüschel, Anna; Jarl, Linnea; Magnusson, Susanna; Windahl, Tove; Johansson, Robert; Carlbring, Per; Andersson, Gerhard

2014-01-09

Evaluating and comparing the effectiveness of two smartphone-delivered treatments: one based on behavioural activation (BA) and other on mindfulness. Parallel randomised controlled, open, trial. Participants were allocated using an online randomisation tool, handled by an independent person who was separate from the staff conducting the study. General community, with recruitment nationally through mass media and advertisements. 40 participants diagnosed with major depressive disorder received a BA treatment, and 41 participants received a mindfulness treatment. 9 participants were lost at the post-treatment. An 8-week long behaviour programme administered via a smartphone application. Mindfulness: An 8-week long mindfulness programme, administered via a smartphone application. The Beck Depression Inventory-II (BDI-II) and the nine-item Patient Health Questionnaire Depression Scale (PHQ-9). 81 participants were randomised (mean age 36.0 years (SD=10.8)) and analysed. Results showed no significant interaction effects of group and time on any of the outcome measures either from pretreatment to post-treatment or from pretreatment to the 6-month follow-up. Subgroup analyses showed that the BA treatment was more effective than the mindfulness treatment among participants with higher initial severity of depression from pretreatment to the 6-month follow-up (PHQ-9: F (1, 362.1)=5.2, p<0.05). In contrast, the mindfulness treatment worked better than the BA treatment among participants with lower initial severity from pretreatment to the 6-month follow-up (PHQ-9: F (1, 69.3)=7.7, p<0.01); BDI-II: (F(1, 53.60)=6.25, p<0.05). The two interventions did not differ significantly from one another. For participants with higher severity of depression, the treatment based on BA was superior to the treatment based on mindfulness. For participants with lower initial severity, the treatment based on mindfulness worked significantly better than the treatment based on BA. Clinical Trials NCT01463020.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

The NEtherlands Cervical Kinematics (NECK) Trial. Cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in the treatment of cervical disc herniation; a double-blind randomised multicenter study

PubMed Central

2010-01-01

Background Patients with cervical radicular syndrome due to disc herniation refractory to conservative treatment are offered surgical treatment. Anterior cervical discectomy is the standard procedure, often in combination with interbody fusion. Accelerated adjacent disc degeneration is a known entity on the long term. Recently, cervical disc prostheses are developed to maintain motion and possibly reduce the incidence of adjacent disc degeneration. A comparative cost-effectiveness study focused on adjacent segment degeneration and functional outcome has not been performed yet. We present the design of the NECK trial, a randomised study on cost-effectiveness of anterior cervical discectomy with or without interbody fusion and arthroplasty in patients with cervical disc herniation. Methods/Design Patients (age 18-65 years) presenting with radicular signs due to single level cervical disc herniation lasting more than 8 weeks are included. Patients will be randomised into 3 groups: anterior discectomy only, anterior discectomy with interbody fusion, and anterior discectomy with disc prosthesis. The primary outcome measure is symptomatic adjacent disc degeneration at 2 and 5 years after surgery. Other outcome parameters will be the Neck Disability Index, perceived recovery, arm and neck pain, complications, re-operations, quality of life, job satisfaction, anxiety and depression assessment, medical consumption, absenteeism, and costs. The study is a randomised prospective multicenter trial, in which 3 surgical techniques are compared in a parallel group design. Patients and research nurses will be kept blinded of the allocated treatment for 2 years. The follow-up period is 5 years. Discussion Currently, anterior cervical discectomy with fusion is the golden standard in the surgical treatment of cervical disc herniation. Whether additional interbody fusion or disc prothesis is necessary and cost-effective will be determined by this trial. Trial Registration Netherlands Trial Register NTR1289 PMID:20553591

The quality of reporting in cluster randomised crossover trials: proposal for reporting items and an assessment of reporting quality.

PubMed

Arnup, Sarah J; Forbes, Andrew B; Kahan, Brennan C; Morgan, Katy E; McKenzie, Joanne E

2016-12-06

The cluster randomised crossover (CRXO) design is gaining popularity in trial settings where individual randomisation or parallel group cluster randomisation is not feasible or practical. Our aim is to stimulate discussion on the content of a reporting guideline for CRXO trials and to assess the reporting quality of published CRXO trials. We undertook a systematic review of CRXO trials. Searches of MEDLINE, EMBASE, and CINAHL Plus as well as citation searches of CRXO methodological articles were conducted to December 2014. Reporting quality was assessed against both modified items from 2010 CONSORT and 2012 cluster trials extension and other proposed quality measures. Of the 3425 records identified through database searching, 83 trials met the inclusion criteria. Trials were infrequently identified as "cluster randomis(z)ed crossover" in title (n = 7, 8%) or abstract (n = 21, 25%), and a rationale for the design was infrequently provided (n = 20, 24%). Design parameters such as the number of clusters and number of periods were well reported. Discussion of carryover took place in only 17 trials (20%). Sample size methods were only reported in 58% (n = 48) of trials. A range of approaches were used to report baseline characteristics. The analysis method was not adequately reported in 23% (n = 19) of trials. The observed within-cluster within-period intracluster correlation and within-cluster between-period intracluster correlation for the primary outcome data were not reported in any trial. The potential for selection, performance, and detection bias could be evaluated in 30%, 81%, and 70% of trials, respectively. There is a clear need to improve the quality of reporting in CRXO trials. Given the unique features of a CRXO trial, it is important to develop a CONSORT extension. Consensus amongst trialists on the content of such a guideline is essential.

Comparison of the therapeutic efficacy of intravenous dimenhydrinate and intravenous piracetam in patients with vertigo: a randomised clinical trial.

PubMed

Doğan, Nurettin Özgür; Avcu, Nazire; Yaka, Elif; Yılmaz, Serkan; Pekdemir, Murat

2015-07-01

The present study aimed to compare the therapeutic efficacy of dimenhydrinate and piracetam in patients with vertigo. A blinded, parallel group, superiority, randomised clinical trial was carried out on patients who presented to the emergency department (ED) with vertigo. Healthy adult patients presenting to the ED with undifferentiated vertigo were included in the study. The efficacy of intravenous dimenhydrinate (100 mg) and intravenous piracetam (2000 mg) for reducing the intensity of vertigo was compared in two randomised treatment groups using a 10-point numeric rating scale (NRS). The determination of NRS scores was performed at presentation and at the 30th minute of presentation, after the study drug was implemented, both in immobile and ambulatory positions. The primary outcome variable was reduction in vertigo intensity documented on the NRS at the 30th minute after medication administration, analysed by intention to treat. A total of 94 patients were included in the randomisation (n=47 in both groups). The baseline NRS scores were 7.55±2.00 in the dimenhydrinate group and 8.19±1.79 in the piracetam group. The changes from baseline for dimenhydrinate and piracetam were 2.92±3.11 and 3.75±3.40 (difference -0.83 (95% CI -2.23 to 0.57)) in the immobile position and were 2.04±3.07 and 2.72±2.91 (difference -0.68 (95% CI -2.03 to 0.67)) in the ambulatory position. Rescue medication need was similar in both treatment groups (p=0.330), and only one adverse reaction was reported. We found no evidence of a difference between dimenhydrinate and piracetam in relieving the symptoms of vertigo. Clinical Trials Registration ID: NCT01890538. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Externally disposed plasma membrane proteins. I. Enzymatic iodination of mouse L cells

PubMed Central

1975-01-01

The enzymatic iodination technique has been utilized in a study of the externally disposed membrane proteins of the mouse L cell. Iodination of cells in suspension results in lactoperoxidase-specific iodide incorporation with no loss of cell viability under the conditions employed, less than 3% lipid labeling, and more than 90% of the labeled species identifiable as monoiodotyrosine. 90% of the incorporated label is localized to the cell surface by electron microscope autoradiography, with 5-10% in the centrosphere region and postulated to represent pinocytic vesicles. Sodium dodecylsulfate-polyacrylamide gels of solubilized L-cell proteins reveals five to six labeled peaks ranging from 50,000 to 200,000 daltons. Increased resolution by use of gradient slab gels reveals 15-20 radioactive bands. Over 60% of the label resides in approximately nine polypeptides of 80,000 to 150,000 daltons. Various controls indicate that the labeling pattern reflects endogenous membrane proteins, not serum components. The incorporated 125-I, cholesterol, and one plasma membrane enzyme marker, alkaline phosphodiesterase I, are purified in parallel when plasma membranes are isolated from intact, iodinated L cells. The labeled components present in a plasma membrane-rich fraction from iodinated cells are identical to those of the total cell, with a 10- to 20-fold enrichment in specific activity of each radioactive peak in the membrane. PMID:163833

A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.

PubMed

Vichinsky, Elliott; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Eckman, James; Lane, Peter; Files, Beatrice; Hassell, Kathryn; Kelly, Patrick; Wilson, Felicia; Bernaudin, Françoise; Forni, Gian Luca; Okpala, Iheanyi; Ressayre-Djaffer, Catherine; Alberti, Daniele; Holland, Jaymes; Marks, Peter; Fung, Ellen; Fischer, Roland; Mueller, Brigitta U; Coates, Thomas

2007-02-01

Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

A pragmatic randomised controlled trial assessing the non-inferiority of counselling for depression versus cognitive-behaviour therapy for patients in primary care meeting a diagnosis of moderate or severe depression (PRaCTICED): Study protocol for a randomised controlled trial.

PubMed

Saxon, David; Ashley, Kate; Bishop-Edwards, Lindsey; Connell, Janice; Harrison, Phillippa; Ohlsen, Sally; Hardy, Gillian E; Kellett, Stephen; Mukuria, Clara; Mank, Toni; Bower, Peter; Bradburn, Mike; Brazier, John; Elliott, Robert; Gabriel, Lynne; King, Michael; Pilling, Stephen; Shaw, Sue; Waller, Glenn; Barkham, Michael

2017-03-01

NICE guidelines state cognitive behavioural therapy (CBT) is a front-line psychological treatment for people presenting with depression in primary care. Counselling for Depression (CfD), a form of Person-Centred Experiential therapy, is also offered within Improving Access to Psychological Therapies (IAPT) services for moderate depression but its effectiveness for severe depression has not been investigated. A full-scale randomised controlled trial to determine the efficacy and cost-effectiveness of CfD is required. PRaCTICED is a two-arm, parallel group, non-inferiority randomised controlled trial comparing CfD against CBT. It is embedded within the local IAPT service using a stepped care service delivery model where CBT and CfD are routinely offered at step 3. Trial inclusion criteria comprise patients aged 18 years or over, wishing to work on their depression, judged to require a step 3 intervention, and meeting an ICD-10 diagnosis of moderate or severe depression. Patients are randomised using a centralised, web-based system to CfD or CBT with each treatment being delivered up to a maximum 20 sessions. Both interventions are manualised with treatment fidelity tested via supervision and random sampling of sessions using adherence/competency scales. The primary outcome measure is the Patient Health Questionnaire-9 collected at baseline, 6 and 12 months. Secondary outcome measures tap depression, generic psychological distress, anxiety, functioning and quality of life. Cost-effectiveness is determined by a patient service receipt questionnaire. Exit interviews are conducted with patients by research assessors blind to treatment allocation. The trial requires 500 patients (250 per arm) to test the non-inferiority hypothesis of -2 PHQ-9 points at the one-sided, 2.5% significance level with 90% power, assuming no underlying difference and a standard deviation of 6.9. The primary analysis will be undertaken on all patients randomised (intent to treat) alongside per-protocol and complier-average causal effect analyses as recommended by the extension to the CONSORT statement for non-inferiority trials. This large-scale trial utilises routinely collected outcome data as well as specific trial data to provide evidence of the comparative efficacy and cost-effectiveness of Counselling for Depression compared with Cognitive Behaviour Therapy as delivered within the UK government's Improving Access to Psychological Therapies initiative. Controlled Trials ISRCTN Registry, ISRCTN06461651 . Registered on 14 September 2014.

The use of systematic reviews in the planning, design and conduct of randomised trials: a retrospective cohort of NIHR HTA funded trials.

PubMed

Jones, Ashley P; Conroy, Elizabeth; Williamson, Paula R; Clarke, Mike; Gamble, Carrol

2013-03-25

A systematic review, with or without a meta-analysis, should be undertaken to determine if the research question of interest has already been answered before a new trial begins. There has been limited research on how systematic reviews are used within the design of new trials, the aims of this study were to investigate how systematic reviews of earlier trials are used in the planning and design of new randomised trials. Documentation from the application process for all randomised trials funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) between 2006 and 2008 were obtained. This included the: commissioning brief (if appropriate), outline application, minutes of the Board meeting in which the outline application was discussed, full application, detailed project description, referee comments, investigator response to referee comments, Board minutes on the full application and the trial protocol. Data were extracted on references to systematic reviews and how any such reviews had been used in the planning and design of the trial. 50 randomised trials were funded by NIHR HTA during this period and documentation was available for 48 of these. The cohort was predominately individually randomised parallel trials aiming to detect superiority between two treatments for a single primary outcome. 37 trials (77.1%) referenced a systematic review within the application and 20 of these (i.e. 41.7% of the total) used information contained in the systematic review in the design or planning of the new trial. The main areas in which systematic reviews were used were in the selection or definition of an outcome to be measured in the trial (7 of 37, 18.9%), the sample size calculation (7, 18.9%), the duration of follow up (8, 21.6%) and the approach to describing adverse events (9, 24.3%). Boards did not comment on the presence/absence or use of systematic reviews in any application. Systematic reviews were referenced in most funded applications but just over half of these used the review to inform the design. There is an expectation from funders that applicants will use a systematic review to justify the need for a new trial but no expectation regarding further use of a systematic review to aid planning and design of the trial. Guidelines for applicants and funders should be developed to promote the use of systematic reviews in the design and planning of randomised trials, to optimise delivery of new studies informed by the most up-to-date evidence base and to minimise waste in research.

Head-to-head comparison of intensive lifestyle intervention (U-TURN) versus conventional multifactorial care in patients with type 2 diabetes: protocol and rationale for an assessor-blinded, parallel group and randomised trial

PubMed Central

Ried-Larsen, Mathias; Hansen, Katrine B; Johansen, Mette Y; Pedersen, Maria; Zacho, Morten; Hansen, Louise S; Kofoed, Katja; Thomsen, Katja; Jensen, Mette S; Nielsen, Rasmus O; MacDonald, Chris; Langberg, Henning; Vaag, Allan A; Pedersen, Bente K; Karstoft, Kristian

2015-01-01

Introduction Current pharmacological therapies in patients with type 2 diabetes (T2D) are challenged by lack of sustainability and borderline firm evidence of real long-term health benefits. Accordingly, lifestyle intervention remains the corner stone in the management of T2D. However, there is a lack of knowledge regarding the optimal intervention programmes in T2D ensuring both compliance as well as long-term health outcomes. Our objective is to assess the effects of an intensive lifestyle intervention (the U-TURN intervention) on glycaemic control in patients with T2D. Our hypothesis is that intensive lifestyle changes are equally effective as standard diabetes care, including pharmacological treatment in maintaining glycaemic control (ie, glycated haemoglobin (HbA1c)) in patients with T2D. Furthermore, we expect that intensive lifestyle changes will decrease the need for antidiabetic medications. Methods and analysis The study is an assessor-blinded, parallel group and a 1-year randomised trial. The primary outcome is change in glycaemic control (HbA1c), with the key secondary outcome being reductions in antidiabetic medication. Participants will be patients with T2D (T2D duration <10 years) without complications who are randomised into an intensive lifestyle intervention (U-TURN) or a standard care intervention in a 2:1 fashion. Both groups will be exposed to the same standardised, blinded, target-driven pharmacological treatment and can thus maintain, increase, reduce or discontinue the pharmacological treatment. The decision is based on the standardised algorithm. The U-TURN intervention consists of increased training and basal physical activity level, and an antidiabetic diet including an intended weight loss. The standard care group as well as the U-TURN group is offered individual diabetes management counselling on top of the pharmacological treatment. Ethics and dissemination This study has been approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-1–2014–114). Positive, negative or inconclusive findings will be disseminated in peer-reviewed journals, at national and international conferences. Trial registration number NCT02417012. PMID:26656025

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis

PubMed Central

Landers, Steve; Hely, Andrew; Harrison, Benjamin; Maister, Nick; Hely, Rachael; Lane, Stephen E; Gill, Stephen D; Page, Richard S

2017-01-01

Introduction Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. Methods and analysis The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Ethics and dissemination Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Trial registration number Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016. PMID:28554913

Effectiveness and micro-costing of the KiVa school-based bullying prevention programme in Wales: study protocol for a pragmatic definitive parallel group cluster randomised controlled trial.

PubMed

Clarkson, Suzy; Axford, Nick; Berry, Vashti; Edwards, Rhiannon Tudor; Bjornstad, Gretchen; Wrigley, Zoe; Charles, Joanna; Hoare, Zoe; Ukoumunne, Obioha C; Matthews, Justin; Hutchings, Judy

2016-02-01

Bullying refers to verbal, physical or psychological aggression repeated over time that is intended to cause harm or distress to the victims who are unable to defend themselves. It is a key public health priority owing to its widespread prevalence in schools and harmful short- and long-term effects on victims' well-being. There is a need to strengthen the evidence base by testing innovative approaches to preventing bullying. KiVa is a school-based bullying prevention programme with universal and indicated elements and an emphasis on changing bystander behaviour. It achieved promising results in a large trial in Finland, and now requires testing in other countries. This paper describes the protocol for a cluster randomised controlled trial (RCT) of KiVa in Wales. The study uses a two-arm waitlist control pragmatic definitive parallel group cluster RCT design with an embedded process evaluation and calculation of unit cost. Participating schools will be randomised a using a 1:1 ratio to KiVa plus usual provision (intervention group) or usual provision only (control group). The trial has one primary outcome, child self-reported victimisation from bullying, dichotomised as 'victimised' (bullied at least twice a month in the last couple of months) versus 'not victimised'. Secondary outcomes are: bullying perpetration; aspects of child social and emotional well-being (including emotional problems, conduct, peer relations, prosocial behaviour); and school attendance. Follow-up is at 12 months post-baseline. Implementation fidelity is measured through teacher-completed lesson records and independent school-wide observation. A micro-costing analysis will determine the costs of implementing KiVa, including recurrent and non-recurrent unit costs. Factors related to the scalability of the programme will be examined in interviews with head teachers and focus groups with key stakeholders in the implementation of school-based bullying interventions. The results from this trial will provide evidence on whether the KiVa programme is transportable from Finland to Wales in terms of effectiveness and implementation. It will provide information about the costs of delivery and generate insights into factors related to the scalability of the programme. Current Controlled Trials ISRCTN23999021 Date 10-6-13.

1,2-Octanediol, a Novel Surfactant, for Treating Head Louse Infestation: Identification of Activity, Formulation, and Randomised, Controlled Trials

PubMed Central

Burgess, Ian F.; Lee, Peter N.; Kay, Katrina; Jones, Ruth; Brunton, Elizabeth R.

2012-01-01

Background Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy. Methods and Findings We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days. Study 1 was a proof of concept with 18/20 (90%) participants cured. Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2–2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RR = 1.50 (97.5% CI, 1.22 to 1.85) for 2–2.5 hours, and 153/174 (87.9%) RR = 1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion. Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2–2.5 hours with 1,2-octanediol alcohol free mousse applied for 2–2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RR = 1.29, 95% CI, 0.95 to 1.75; NNT = 5.7) but mousse applied for 2–2.5 hours 17/41 (41.5%) was less effective than lotion (RR = 0.69, 95% CI, 0.44 to 1.08). Adverse events were more common using 1,2-octanediol lotion at both 2–2.5 hours (12.0%, p = 0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse. Conclusions 1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect's cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions. Trial registrations Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846 PMID:22523593

1,2-Octanediol, a novel surfactant, for treating head louse infestation: identification of activity, formulation, and randomised, controlled trials.

PubMed

Burgess, Ian F; Lee, Peter N; Kay, Katrina; Jones, Ruth; Brunton, Elizabeth R

2012-01-01

Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy. We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days. Study 1 was a proof of concept with 18/20 (90%) participants cured. Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2-2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RR = 1.50 (97.5% CI, 1.22 to 1.85) for 2-2.5 hours, and 153/174 (87.9%) RR = 1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion. Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2-2.5 hours with 1,2-octanediol alcohol free mousse applied for 2-2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RR = 1.29, 95% CI, 0.95 to 1.75; NNT = 5.7) but mousse applied for 2-2.5 hours 17/41 (41.5%) was less effective than lotion (RR = 0.69, 95% CI, 0.44 to 1.08). Adverse events were more common using 1,2-octanediol lotion at both 2-2.5 hours (12.0%, p = 0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse. 1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect's cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions. Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846.

Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis.

PubMed

Landers, Steve; Hely, Andrew; Harrison, Benjamin; Maister, Nick; Hely, Rachael; Lane, Stephen E; Gill, Stephen D; Page, Richard S

2017-05-29

Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Three-dimensional, task-specific robot therapy of the arm after stroke: a multicentre, parallel-group randomised trial.

PubMed

Klamroth-Marganska, Verena; Blanco, Javier; Campen, Katrin; Curt, Armin; Dietz, Volker; Ettlin, Thierry; Felder, Morena; Fellinghauer, Bernd; Guidali, Marco; Kollmar, Anja; Luft, Andreas; Nef, Tobias; Schuster-Amft, Corina; Stahel, Werner; Riener, Robert

2014-02-01

Arm hemiparesis secondary to stroke is common and disabling. We aimed to assess whether robotic training of an affected arm with ARMin--an exoskeleton robot that allows task-specific training in three dimensions-reduces motor impairment more effectively than does conventional therapy. In a prospective, multicentre, parallel-group randomised trial, we enrolled patients who had had motor impairment for more than 6 months and moderate-to-severe arm paresis after a cerebrovascular accident who met our eligibility criteria from four centres in Switzerland. Eligible patients were randomly assigned (1:1) to receive robotic or conventional therapy using a centre-stratified randomisation procedure. For both groups, therapy was given for at least 45 min three times a week for 8 weeks (total 24 sessions). The primary outcome was change in score on the arm (upper extremity) section of the Fugl-Meyer assessment (FMA-UE). Assessors tested patients immediately before therapy, after 4 weeks of therapy, at the end of therapy, and 16 weeks and 34 weeks after start of therapy. Assessors were masked to treatment allocation, but patients, therapists, and data analysts were unmasked. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00719433. Between May 4, 2009, and Sept 3, 2012, 143 individuals were tested for eligibility, of whom 77 were eligible and agreed to participate. 38 patients assigned to robotic therapy and 35 assigned to conventional therapy were included in analyses. Patients assigned to robotic therapy had significantly greater improvements in motor function in the affected arm over the course of the study as measured by FMA-UE than did those assigned to conventional therapy (F=4.1, p=0.041; mean difference in score 0.78 points, 95% CI 0.03-1.53). No serious adverse events related to the study occurred. Neurorehabilitation therapy including task-oriented training with an exoskeleton robot can enhance improvement of motor function in a chronically impaired paretic arm after stroke more effectively than conventional therapy. However, the absolute difference between effects of robotic and conventional therapy in our study was small and of weak significance, which leaves the clinical relevance in question. Swiss National Science Foundation and Bangerter-Rhyner Stiftung. Copyright © 2014 Elsevier Ltd. All rights reserved.

Collaborative labeling of malignant glioma with WebMILL: a first look

NASA Astrophysics Data System (ADS)

Singh, Eesha; Asman, Andrew J.; Xu, Zhoubing; Chambless, Lola; Thompson, Reid; Landman, Bennett A.

2012-02-01

Malignant gliomas are the most common form of primary neoplasm in the central nervous system, and one of the most rapidly fatal of all human malignancies. They are treated by maximal surgical resection followed by radiation and chemotherapy. Herein, we seek to improve the methods available to quantify the extent of tumors using newly presented, collaborative labeling techniques on magnetic resonance imaging. Traditionally, labeling medical images has entailed that expert raters operate on one image at a time, which is resource intensive and not practical for very large datasets. Using many, minimally trained raters to label images has the possibility of minimizing laboratory requirements and allowing high degrees of parallelism. A successful effort also has the possibility of reducing overall cost. This potentially transformative technology presents a new set of problems, because one must pose the labeling challenge in a manner accessible to people with little or no background in labeling medical images and raters cannot be expected to read detailed instructions. Hence, a different training method has to be employed. The training must appeal to all types of learners and have the same concepts presented in multiple ways to ensure that all the subjects understand the basics of labeling. Our overall objective is to demonstrate the feasibility of studying malignant glioma morphometry through statistical analysis of the collaborative efforts of many, minimally-trained raters. This study presents preliminary results on optimization of the WebMILL framework for neoplasm labeling and investigates the initial contributions of 78 raters labeling 98 whole-brain datasets.

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

PubMed

Azizi, Michel; Sapoval, Marc; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Midulla, Marco; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Trillaud, Hervé; Pereira, Helena; Plouin, Pierre-François; Chatellier, Gilles

2015-05-16

Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. French Ministry of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness of the 'Who's Challenging Who' support staff training intervention to improve attitudes and empathy towards adults with intellectual disability and challenging behaviours: study protocol for a cluster randomised controlled trial.

PubMed

Randell, Elizabeth; Hastings, Richard P; McNamara, Rachel; Knight, Roseanna; Gillespie, David; Taylor, Zachary

2017-10-05

Findings suggest approximately one in six people with intellectual disability engage in 'challenging behaviours', which include aggression towards others/property and self-injurious actions. In residential settings, actions of staff members can make challenging behaviours more likely to occur, or make these behaviours worse. In particular, negative attitudes from members of staff and lack of understanding about the reasons for challenging behaviour are contributory factors. 'Who's Challenging Who?' (WCW) training is designed to emphasise the role of staff in residential settings as a challenge also to people with intellectual disability. The course is delivered jointly by a trainer with intellectual disability who has been labelled as having challenging behaviour, along with a trainer without intellectual disability. This is a cluster randomised two-arm trial of WCW training versus a waiting list control. Overall, 118 residential settings will be recruited and randomised on a 1:1 ratio. Within each setting, two members of staff will be invited to take part in the trial. Participants will complete assessments at baseline and at 6 and 20 weeks. WCW is a half day initial training course with some follow-on coaching to ensure implementation. The primary outcome is changes in staff empathy towards people with challenging behaviour. Secondary outcomes at the staff level include confidence, attitudes and work-related well-being. Secondary outcomes at the residential setting level include recorded incidents of aggressive challenging behaviour, and use of any restrictive practices. If the results of the cluster randomised trial are positive, we will disseminate the findings widely and make all training manuals and materials freely available for anyone in intellectual disability services (and beyond) to use. Our training approach may have wider implications in other areas of social care. It may also provide a generally applicable model for how to train people with intellectual disability to act as co-trainers in intellectual disability social care settings. People with intellectual disability and challenging behaviour have already been involved centrally with the design, development and pilot evaluation of WCW and will also be fully involved throughout this trial. Registered on the International Standard Randomised Controlled Trial Number registry on 8th December 2015: ISRCTN53763600 .

Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

Objective To explore the risk of industry sponsorship bias in a systematically identified set of placebo controlled and active comparator trials of statins. Design Systematic review and network meta-analysis. Eligibility Open label and double blind randomised controlled trials comparing one statin with another at any dose or with control (placebo, diet, or usual care) for adults with, or at risk of developing, cardiovascular disease. Only trials that lasted longer than four weeks with more than 50 participants per trial arm were included. Two investigators assessed study eligibility. Data sources Bibliographic databases and reference lists of relevant articles published between 1 January 1985 and 10 March 2013. Data extraction One investigator extracted data and another confirmed accuracy. Main outcome measure Mean absolute change from baseline concentration of low density lipoprotein (LDL) cholesterol. Data synthesis Study level outcomes from randomised trials were combined using random effects network meta-analyses. Results We included 183 randomised controlled trials of statins, 103 of which were two-armed or multi-armed active comparator trials. When all of the existing randomised evidence was synthesised in network meta-analyses, there were clear differences in the LDL cholesterol lowering effects of individual statins at different doses. In general, higher doses resulted in higher reductions in baseline LDL cholesterol levels. Of a total of 146 industry sponsored trials, 64 were placebo controlled (43.8%). The corresponding number for the non-industry sponsored trials was 16 (43.2%). Of the 35 unique comparisons available in 37 non-industry sponsored trials, 31 were also available in industry sponsored trials. There were no systematic differences in magnitude between the LDL cholesterol lowering effects of individual statins observed in industry sponsored versus non-industry sponsored trials. In industry sponsored trials, the mean change from baseline LDL cholesterol level was on average 1.77 mg/dL (95% credible interval −11.12 to 7.66) lower than the change observed in non-industry sponsored trials. There was no detectable inconsistency in the evidence network. Conclusions Our analysis shows that the findings obtained from industry sponsored statin trials seem similar in magnitude as those in non-industry sources. There are actual differences in the effectiveness of individual statins at various doses that explain previously observed discrepancies between industry and non-industry sponsored trials. PMID:25281681

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial.

PubMed

Dat, Vu Quoc; Geskus, Ronald B; Wolbers, Marcel; Loan, Huynh Thi; Yen, Lam Minh; Binh, Nguyen Thien; Chien, Le Thanh; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Lan, Nguyen Phu Huong; Hao, Nguyen Van; Long, Hoang Bao; Thuy, Tran Phuong; Kinh, Nguyen Van; Trung, Nguyen Vu; Phu, Vu Dinh; Cap, Nguyen Trung; Trinh, Dao Tuyet; Campbell, James; Kestelyn, Evelyne; Wertheim, Heiman F L; Wyncoll, Duncan; Thwaites, Guy Edward; van Doorn, H Rogier; Thwaites, C Louise; Nadjm, Behzad

2018-04-04

Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay. This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay. ClinicalTrials.gov, NCT02966392 . Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

PubMed

Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

2016-01-01

The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian). Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 10(10) pu, 35 [38%] to 2·5 × 10(10) pu, 35 [38%] to 5 × 10(10) pu, and 11 [12%] to 1 × 10(11) pu) and 20 in the USA (ten [50%] to 1 × 10(10) pu and ten [50%] to 1 × 10(11) pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 10(10) and two [2%] received 1 × 10(11) pu) and four (20%) of 20 in the USA (all received 1 × 10(11) pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness. 1 × 10(11) pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers). Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases. Copyright © 2016 Tapia et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Continuous wound infiltration versus epidural analgesia after hepato-pancreato-biliary surgery (POP-UP): a randomised controlled, open-label, non-inferiority trial.

PubMed

Mungroop, Timothy H; Veelo, Denise P; Busch, Olivier R; van Dieren, Susan; van Gulik, Thomas M; Karsten, Tom M; de Castro, Steve M; Godfried, Marc B; Thiel, Bram; Hollmann, Markus W; Lirk, Philipp; Besselink, Marc G

2016-10-01

Epidural analgesia is the international standard for pain treatment in abdominal surgery. Although some studies have advocated continuous wound infiltration with local anaesthetics, robust evidence is lacking, especially on patient-reported outcome measures. We aimed to determine the effectiveness of continuous wound infiltration in hepato-pancreato-biliary surgery. In this randomised controlled, open label, non-inferiority trial (POP-UP), we enrolled adult patients undergoing hepato-pancreato-biliary surgery by subcostal or midline laparotomy in two Dutch hospitals. Patients were centrally randomised (1:1) to receive either pain treatment with continuous wound infiltration using bupivacaine plus patient-controlled analgesia with morphine or to receive (patient-controlled) epidural analgesia with bupivacaine and sufentanil. All patients were treated within an enhanced recovery setting. Randomisation was stratified by centre and type of incision. The primary outcome was the mean Overall Benefit of Analgesic Score (OBAS) from day 1-5, a validated composite endpoint of pain scores, opioid side-effects, and patient satisfaction (range 0 [best] to 28 [worst]). Analysis was per-protocol. The non-inferiority limit of the mean difference was + 3·0. This trial is registered with the Netherlands Trial Registry, number NTR4948. Between Jan 20, 2015, and Sept 16, 2015, we randomly assigned 105 eligible patients: 53 to receive continuous wound infiltration and 52 to receive epidural analgesia. One patient in the continuous wound infiltration group discontinued treatment, as did five in the epidural analgesia group; of these five patients, preoperative placement failed in three (these patients were treated with continuous wound infiltration instead), one patient refused an epidural, and data for the primary endpoint was lost for one. Thus, 55 patients were included in the continuous wound infiltration group and 47 in the epidural analgesia group for the per-protocol analyses. Mean OBAS was 3·8 (SD 2·4) in the continuous wound infiltration group versus 4·4 (2·2) in the epidural group (mean difference -0·62, 95% CI -1·54 to 0·30). Because the upper bound of the one-sided 95% CI did not exceed +3·0, non-inferiority was shown. Four (7%) patients in the continuous wound infiltration group and five (11%) of those in the epidural group had an adverse event. One patient in the continuous wound infiltration group had a serious adverse event (temporary hypotension and arrhythmia after bolus injection); no serious adverse events were noted in the epidural group. These data suggest that continuous wound infiltration is non-inferior to epidural analgesia in hepato-pancreato-biliary surgery within an enhanced recovery setting. Further large-scale trials are required to make a definitive assessment of non-inferiority. Academic Medical Centre, Amsterdam, Netherlands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 5. Speech outcomes in 5-year-olds - consonant proficiency and errors.

PubMed

Willadsen, Elisabeth; Lohmander, Anette; Persson, Christina; Lundeborg, Inger; Alaluusua, Suvi; Aukner, Ragnhild; Bau, Anja; Boers, Maria; Bowden, Melanie; Davies, Julie; Emborg, Berit; Havstam, Christina; Hayden, Christine; Henningsson, Gunilla; Holmefjord, Anders; Hölttä, Elina; Kisling-Møller, Mia; Kjøll, Lillian; Lundberg, Maria; McAleer, Eilish; Nyberg, Jill; Paaso, Marjukka; Pedersen, Nina Helen; Rasmussen, Therese; Reisæter, Sigvor; Andersen, Helene Søgaard; Schöps, Antje; Tørdal, Inger-Beate; Semb, Gunvor

2017-02-01

Normal articulation before school start is a main objective in cleft palate treatment. The aim was to investigate if differences exist in consonant proficiency at age 5 years between children with unilateral cleft lip and palate (UCLP) randomised to different surgical protocols for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Norway, Sweden, and the UK. Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with non-syndromic UCLP. Speech audio- and video-recordings of 391 children (136 girls and 255 boys) were available and transcribed phonetically. The main outcome measure was Percent Consonants Correct (PCC) from blinded assessments. In Trial 1, arm A showed statistically significant higher PCC scores (82%) than arm B (78%) (p = .045). No significant differences were found between prevalences in Trial 2, A: 79%, C: 82%; or Trial 3, A: 80%, D: 85%. Across all trials, girls achieved better PCC scores, excluding s-errors, than boys (91.0% and 87.5%, respectively) (p = .01). PCC scores were higher in arm A than B in Trial 1, whereas no differences were found between arms in Trials 2 or 3. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed. ISRCTN29932826.

Supervised pelvic floor muscle training versus attention-control massage treatment in patients with faecal incontinence: Statistical analysis plan for a randomised controlled trial.

PubMed

Ussing, Anja; Dahn, Inge; Due, Ulla; Sørensen, Michael; Petersen, Janne; Bandholm, Thomas

2017-12-01

Faecal incontinence affects approximately 8-9% of the adult population. The condition is surrounded by taboo; it can have a devastating impact on quality of life and lead to major limitations in daily life. Pelvic floor muscle training in combination with information and fibre supplements is recommended as first-line treatment for faecal incontinence. Despite this, the effect of pelvic floor muscle training for faecal incontinence is unclear. No previous trials have investigated the efficacy of supervised pelvic floor muscle training in combination with conservative treatment and compared this to an attention-control massage treatment including conservative treatment. The aim of this trial is to investigate if 16 weeks of supervised pelvic floor muscle training in combination with conservative treatment is superior to attention-control massage treatment and conservative treatment in patients with faecal incontinence. Randomised, controlled, superiority trial with two parallel arms. 100 participants with faecal incontinence will be randomised to either (1) individually supervised pelvic floor muscle training and conservative treatment or (2) attention-control massage treatment and conservative treatment. The primary outcome is participants' rating of symptom changes after 16 weeks of treatment using the Patient Global Impression of Improvement Scale. Secondary outcomes are the Vaizey Incontinence Score, the Fecal Incontinence Severity Index, the Fecal Incontinence Quality of Life Scale, a 14-day bowel diary, anorectal manometry and rectal capacity measurements. Follow-up assessment at 36 months will be conducted. This paper describes and discusses the rationale, the methods and in particular the statistical analysis plan of this trial.

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers

PubMed Central

Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

2013-01-01

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32·0% ± 47·3% versus 97·1% ± 7·0% (P < 0·001) after 4 weeks, whereas at 6 weeks wounds were reduced by −1·8% ± 70·3% versus 98·4% ± 5·8% (P < 0·001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0·001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. PMID:23742102

Randomised controlled trial of reflexology for menopausal symptoms.

PubMed

Williamson, Jan; White, Adrian; Hart, Anna; Ernst, Edzard

2002-09-01

Clinical experience suggests that reflexology may have beneficial effects on the symptoms occurring in menopausal women, particularly psychological symptoms. This study aims to examine that effect rigorously. Randomised controlled trial with two parallel arms. School of Complementary Health in Exeter, Devon, UK. Seventy-six women, aged between 45 and 60 years, reporting menopausal symptoms. Women were randomised to receive nine sessions of either reflexology or nonspecific foot massage (control) by four qualified reflexologists given over a period of 19 weeks. The Women's Health Questionnaire (WHQ), the primary measures being the subscores for anxiety and depression. Severity (visual analogue scale, VAS) and frequency of flushes and night sweats. Mean (SD) scores for anxiety fell from 0.43 (0.29) to 0.22 (0.25) in the reflexology group and from 0.37 (0.27) to 0.27 (0.29) in the control group over the course of treatment. Mean (SD) scores for depression fell from 0.37 (0.25) to 0.20 (0.24) in the reflexology group and from 0.36 (0.23) to 0.20 (0.21) in the control (foot massage) group over the same period. For both scores there was strong evidence of a time effect (P < 0.001) but no evidence of a time-group interaction (P > 0.2). Similar changes were found for severity of hot flushes and night sweats. In the control group, 14/37 believed they had not received true reflexology. Foot reflexology was not shown to be more effective than non-specific foot massage in the treatment of psychological symptoms occurring during the menopause.

Electroacupuncture for insomnia disorder: study protocol for a randomized controlled trial.

PubMed

Kim, Sung-Phil; Kim, Joo-Hee; Kim, Bo-Kyung; Kim, Hyeong-Jun; Jung, In Chul; Cho, Jung Hyo; Kim, Jung-Eun; Kim, Mi-Kyung; Kwon, O-Jin; Kim, Ae-Ran; Park, Hyo-Ju; Seo, Bok-Nam

2017-04-13

Insomnia is a common sleep disorder that affects many adults either transiently or chronically. The societal cost of insomnia is on the rise, while long-term use of current drug treatments can involve adverse effects. Recently, electroacupuncture (EA) has been used to treat various conditions including insomnia. The objective of this study is to provide scientific evidence for the effect and safety of using EA to treat insomnia. In this multicentre, assessor-blind, three-arm, parallel-design, randomised controlled trial, 150 participants will be assigned to the EA group, the sham EA (SEA) group, or the usual care group. The EA and SEA groups will receive the specific treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the usual care group will not receive EA and will continue with usual care during the same time period. The primary outcome measure will be changes in the Insomnia Severity Index 5 weeks after randomisation. The secondary outcomes will include the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and cortisol, and the Patient Global Impression of Change. Safety will be assessed at each visit. The results of this multicentre randomised controlled trial will contribute to provide rigorous clinical evidence for the effects and safety of EA for insomnia disorder. Korean Clinical Trial Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively registered). Date of enrolment of the first participant to the trial 13 October 2015.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2015-12-03

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

The effect of using mobile applications for improving oral hygiene in patients with orthodontic fixed appliances: a randomised controlled trial.

PubMed

Alkadhi, Omar H; Zahid, Mohammed N; Almanea, Read S; Althaqeb, Husam K; Alharbi, Turki H; Ajwa, Nancy M

2017-09-01

To investigate the effect of using mobile applications active reminders to improve oral hygiene in comparison to verbal oral hygiene instructions. Two-arm parallel randomised controlled trial. orthodontic clinics at two branches of a university hospitals of the college of dentistry of Riyadh Colleges of Dentistry and Pharmacy, Riyadh, Saudi Arabia. Forty-four 12-year-old and older subjects. Subjects undergoing orthodontic treatment with fixed appliances were randomly assigned to one of two groups using simple randomisation. Group I: subjects received a mobile application that sends active reminders of oral hygiene three times a day (n = 22). Group II: subjects received verbal oral hygiene instructions verbally during their routine orthodontic visits (n = 22). Two primary outcomes were assessed using plaque index (PI) and gingival index (GI) for Ramfjord teeth to evaluate the level of oral hygiene at baseline and after 4 weeks. Mean differences for PI and GI for group I were reduced from T1 to T2 (P < 0.05, P < 0.05) but did not significantly change for group II (P > 0.05, P > 0.05). Both PI and GI significantly reduced for group I compared to group II between T1 and T2 (P < 0.05, P < 0.05). PI and GI all significantly decreased after 4 weeks of using active reminders of oral hygiene instructions on mobile application compared to verbal oral hygiene instructions. The study was registered at clinicaltrials.gov with number: NCT03109769.

Patient and family satisfaction levels in the intensive care unit after elective cardiac surgery: study protocol for a randomised controlled trial of a preoperative patient education intervention.

PubMed

Lai, Veronica Ka Wai; Lee, Anna; Leung, Patricia; Chiu, Chun Hung; Ho, Ka Man; Gomersall, Charles David; Underwood, Malcolm John; Joynt, Gavin Matthew

2016-06-22

Patients and their families are understandably anxious about the risk of complications and unfamiliar experiences following cardiac surgery. Providing information about postoperative care in the intensive care unit (ICU) to patients and families may lead to lower anxiety levels, and increased satisfaction with healthcare. The objectives of this study are to evaluate the effectiveness of preoperative patient education provided for patients undergoing elective cardiac surgery. 100 patients undergoing elective coronary artery bypass graft, with or without valve replacement surgery, will be recruited into a 2-group, parallel, superiority, double-blinded randomised controlled trial. Participants will be randomised to either preoperative patient education comprising of a video and ICU tour with standard care (intervention) or standard education (control). The primary outcome measures are the satisfaction levels of patients and family members with ICU care and decision-making in the ICU. The secondary outcome measures are patient anxiety and depression levels before and after surgery. Ethical approval has been obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (reference number CREC 2015.308). The findings will be presented at conferences and published in peer-reviewed journals. Study participants will receive a 1-page plain language summary of results. ChiCTR-IOR-15006971. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cost-effectiveness of exercise as a therapy for behavioural and psychological symptoms of dementia within the EVIDEM-E randomised controlled trial.

PubMed

D'Amico, Francesco; Rehill, Amritpal; Knapp, Martin; Lowery, David; Cerga-Pashoja, Arlinda; Griffin, Mark; Iliffe, Steve; Warner, James

2016-06-01

Although available evidence is modest, exercise could be beneficial in reducing behavioural and psychological symptoms of dementia. We aim to evaluate the cost-effectiveness of a dyadic exercise regimen for individuals with dementia and their main carer as therapy for behavioural and psychological symptoms of dementia. Cost-effectiveness analysis within a two-arm, pragmatic, randomised, controlled, single-blind, parallel-group trial of a dyadic exercise regimen (individually tailored, for 20-30 min at least five times per week). The study randomised 131 community-dwelling individuals with dementia and clinically significant behavioural and psychological symptoms with a carer willing and able to participate in the exercise regimen; 52 dyads provided sufficient cost data for analyses. Mean intervention cost was £284 per dyad. For the subsample of 52 dyads, the intervention group had significantly higher mean cost from a societal perspective (mean difference £2728.60, p = 0.05), but costs were not significantly different from a health and social care perspective. The exercise intervention was more cost-effective than treatment as usual from both societal and health and social care perspectives for the measure of behavioural and psychological symptoms (Neuropsychiatric Inventory). It does not appear cost-effective in terms of cost per quality-adjusted life year gain. The exercise intervention has the potential to be seen as cost-effective when considering behavioural and psychological symptoms but did not appear cost-effective when considering quality-adjusted life year gains. Copyright © 2015 John Wiley & Sons, Ltd.

A self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy: a randomised controlled trial (the SELF study).

PubMed

Littlewood, Chris; Bateman, Marcus; Brown, Kim; Bury, Julie; Mawson, Sue; May, Stephen; Walters, Stephen J

2016-07-01

To evaluate the clinical effectiveness of a self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. Multi-centre pragmatic unblinded parallel group randomised controlled trial. UK National Health Service. Patients with a clinical diagnosis of rotator cuff tendinopathy. The intervention was a programme of self-managed exercise prescribed by a physiotherapist in relation to the most symptomatic shoulder movement. The control group received usual physiotherapy treatment. The primary outcome measure was the Shoulder Pain & Disability Index (SPADI) at three months. Secondary outcomes included the SPADI at six and twelve months. A total of 86 patients (self-managed loaded exercise n=42; usual physiotherapy n=44) were randomised. Twenty-six patients were excluded from the analysis because of lack of primary outcome data at the 3 months follow-up, leaving 60 (n=27; n=33) patients for intention to treat analysis. For the primary outcome, the mean SPADI score at three months was 32.4 (SD 20.2) for the self-managed group, and 30.7 (SD 19.7) for the usual physiotherapy treatment group; mean difference adjusted for baseline score: 3.2 (95% Confidence interval -6.0 to +12.4 P = 0.49).By six and twelve months there remained no significant difference between the groups. This study does not provide sufficient evidence of superiority of one intervention over the other in the short-, mid- or long-term and hence a self-management programme based around a single exercise appears comparable to usual physiotherapy treatment. © The Author(s) 2015.

Randomised controlled trial of a brief intervention targeting predominantly non-verbal communication in general practice consultations.

PubMed

Little, Paul; White, Peter; Kelly, Joanne; Everitt, Hazel; Mercer, Stewart

2015-06-01

The impact of changing non-verbal consultation behaviours is unknown. To assess brief physician training on improving predominantly non-verbal communication. Cluster randomised parallel group trial among adults aged ≥16 years attending general practices close to the study coordinating centres in Southampton. Sixteen GPs were randomised to no training, or training consisting of a brief presentation of behaviours identified from a prior study (acronym KEPe Warm: demonstrating Knowledge of the patient; Encouraging [back-channelling by saying 'hmm', for example]; Physically engaging [touch, gestures, slight lean]; Warm-up: cool/professional initially, warming up, avoiding distancing or non-verbal cut-offs at the end of the consultation); and encouragement to reflect on videos of their consultation. Outcomes were the Medical Interview Satisfaction Scale (MISS) mean item score (1-7) and patients' perceptions of other domains of communication. Intervention participants scored higher MISS overall (0.23, 95% confidence interval [CI] = 0.06 to 0.41), with the largest changes in the distress-relief and perceived relationship subscales. Significant improvement occurred in perceived communication/partnership (0.29, 95% CI = 0.09 to 0.49) and health promotion (0.26, 95% CI = 0.05 to 0.46). Non-significant improvements occurred in perceptions of a personal relationship, a positive approach, and understanding the effects of the illness on life. Brief training of GPs in predominantly non-verbal communication in the consultation and reflection on consultation videotapes improves patients' perceptions of satisfaction, distress, a partnership approach, and health promotion. © British Journal of General Practice 2015.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

PubMed

Taylor, M A; Reilly, D; Llewellyn-Jones, R H; McSharry, C; Aitchison, T C

To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. Randomised, double blind, placebo controlled, parallel group, multicentre study. Four general practices and a hospital ear, nose, and throat outpatient department. 51 patients with perennial allergic rhinitis. Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Impact of referral letters on scheduling of hospital appointments: a randomised control trial.

PubMed

Jiwa, Moyez; Meng, Xingqiong; O'Shea, Carolyn; Magin, Parker; Dadich, Ann; Pillai, Vinita

2014-07-01

Communication is essential for triage, but intervention trials to improve it are scarce. Referral Writer (RW), a referral letter software program, enables documentation of clinical data and extracts relevant patient details from clinical software. To evaluate whether specialists are more confident about scheduling appointments when they receive more information in referral letters. Single-blind, parallel-groups, controlled design with a 1:1 randomisation. Australian GPs watched video vignettes virtually. GPs wrote referral letters after watching vignettes of patients with cancer symptoms. Letter content was scored against a benchmark. The proportions of referral letters triagable by a specialist with confidence, and in which the specialist was confident the patient had potentially life-limiting pathology were determined. Categorical outcomes were tested with χ(2) and continuous outcomes with t-tests. A random-effects logistic model assessed the influence of group randomisation (RW versus control), GP demographics, clinical specialty, and specialist referral assessor on specialist confidence in the information provided. The intervention (RW) group referred more patients and scored significantly higher on information relayed (mean difference 21.6 [95% confidence intervals {CI} = 20.1 to 23.2]). There was no difference in the proportion of letters for which specialists were confident they had sufficient information for appointment scheduling (RW 77.7% versus control 80.6%, P = 0.16). In the logistic model, limited agreement among specialists contributed substantially to the observed differences in appointment scheduling (P = 35% [95% CI 16% to 59%]). In isolation, referral letter templates are unlikely to improve the scheduling of specialist appointments, even when more information is relayed. © British Journal of General Practice 2014.

Valbenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

PubMed

Citrome, Leslie

2017-07-01

The objective of this systematic review was to describe the efficacy, tolerability, and safety of valbenazine for the treatment of tardive dyskinesia (TD). The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'valbenazine' OR 'NBI-98854', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labeling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information. Valbenazine, a reversible inhibitor of Vesicular Monoamine Transporter Type 2 (VMAT2), received approval for the treatment of TD in adults based on a clinical trial development programme that included three 6-week parallel group, randomised, placebo-controlled studies, including one Phase III trial described in product labeling. The recommended dose for valbenazine is 80 mg/d. The percentage of responders in the Phase III acute study, as defined by ≥50% reduction from baseline in the Abnormal Involuntary Movement Scale dyskinesia score was 40.0% for valbenazine 80 mg/d vs 8.7% for placebo, yielding a NNT of 4 (95% CI 3-6). As pooled from available data, discontinuation rates because of an adverse event were 2.9% for valbenazine-treated patients vs 1.6% for placebo-treated patients, resulting in a NNH of 76 (ns). The only adverse event that met the threshold of incidence ≥5% for valbenazine and a rate of ≥2 times than that observed with placebo was somnolence (somnolence, fatigue, sedation), with rates of 10.9% for valbenazine (all doses) vs 4.2% for placebo, resulting in a NNH of 15 (95% CI 9-52). An additional warning and precaution is that valbenazine can prolong the ECG QT interval, however, the valbenazine product label does not contain any bolded boxed warnings or contraindications. Valbenazine is presently the only US Food and Drug Administration-approved agent specifically indicated for the treatment of TD. Valbenazine is about 15 times more likely to result in a response than in a discontinuation because of an adverse event. Head-to-head comparisons with other VMAT2 inhibitors among patients with TD in the 'real world' are needed. © 2017 John Wiley & Sons Ltd.

Testing warning messages on smokers' cigarette packages: a standardised protocol.

PubMed

Brewer, Noel T; Hall, Marissa G; Lee, Joseph G L; Peebles, Kathryn; Noar, Seth M; Ribisl, Kurt M

2016-03-01

Lab experiments on cigarette warnings typically use a brief one-time exposure that is not paired with the cigarette packs smokers use every day, leaving open the question of how repeated warning exposure over several weeks may affect smokers. This proof of principle study sought to develop a new protocol for testing cigarette warnings that better reflects real-world exposure by presenting them on cigarette smokers' own packs. We tested a cigarette pack labelling protocol with 76 US smokers ages 18 and older. We applied graphic warnings to the front and back of smokers' cigarette packs. Most smokers reported that at least 75% of the packs of cigarettes they smoked during the study had our warnings. Nearly all said they would participate in the study again. Using cigarette packs with the study warnings increased quit intentions (p<0.05). Our findings suggest a feasible pack labelling protocol with six steps: (1) schedule appointments at brief intervals; (2) determine typical cigarette consumption; (3) ask smokers to bring a supply of cigarette packs to study appointments; (4) apply labels to smokers' cigarette packs; (5) provide participation incentives at the end of appointments; and (6) refer smokers to cessation services at end of the study. When used in randomised controlled trials in settings with real-world message exposure over time, this protocol may help identify the true impact of warnings and thus better inform tobacco product labelling policy. NCT02247908. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Neurocognitive effects of an omega-3 fatty acid and vitamins E+C in schizophrenia: A randomised controlled trial.

PubMed

Bentsen, H; Landrø, N I

2017-10-16

There is need for more efficient treatment of neurocognitive deficits in schizophrenia. In this 16 weeks randomised, placebo-controlled trial, we examined neurocognitive effects of adding ethyl-eicosapentaenoate 2g/day and/or vitamins E 364mg/day + C 1000mg/day to antipsychotics in 53 patients aged 18-39 years with acute schizophrenia. For the sake of validating neurocognitive tests, healthy subjects, not taking trial drugs, were also included in the study. Ethyl-EPA given alone to patients with low baseline RBC polyunsaturated fatty acids (PUFA), and Vitamins E+C given alone to high PUFA patients, impaired sustained attention (Continuous Performance Test, CPT-IP d prime score), standardised effect sizes d = 0.78 and d = 0.69, respectively. These adverse effects were paralleled by excessive increases in long-chain PUFA and serum alpha-tocopherol, respectively. They were counteracted by combining ethyl-EPA and vitamins, d = 0.80 and d = 0.74 in low and high PUFA patients, respectively. No other neurocognitive tests yielded significant results. Plausible mechanisms of harmful effects are oxidative stress and lipid raft disruption. Copyright © 2017. Published by Elsevier Ltd.

A Bayesian adaptive design for biomarker trials with linked treatments.

PubMed

Wason, James M S; Abraham, Jean E; Baird, Richard D; Gournaris, Ioannis; Vallier, Anne-Laure; Brenton, James D; Earl, Helena M; Mander, Adrian P

2015-09-01

Response to treatments is highly heterogeneous in cancer. Increased availability of biomarkers and targeted treatments has led to the need for trial designs that efficiently test new treatments in biomarker-stratified patient subgroups. We propose a novel Bayesian adaptive randomisation (BAR) design for use in multi-arm phase II trials where biomarkers exist that are potentially predictive of a linked treatment's effect. The design is motivated in part by two phase II trials that are currently in development. The design starts by randomising patients to the control treatment or to experimental treatments that the biomarker profile suggests should be active. At interim analyses, data from treated patients are used to update the allocation probabilities. If the linked treatments are effective, the allocation remains high; if ineffective, the allocation changes over the course of the trial to unlinked treatments that are more effective. Our proposed design has high power to detect treatment effects if the pairings of treatment with biomarker are correct, but also performs well when alternative pairings are true. The design is consistently more powerful than parallel-groups stratified trials. This BAR design is a powerful approach to use when there are pairings of biomarkers with treatments available for testing simultaneously.

Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

PubMed

Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

2009-01-01

To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

INfluence of Successful Periodontal Intervention in REnal Disease (INSPIRED): study protocol for a randomised controlled pilot clinical trial.

PubMed

Sharma, Praveen; Cockwell, Paul; Dietrich, Thomas; Ferro, Charles; Ives, Natalie; Chapple, Iain L C

2017-11-13

Patients with chronic kidney disease (CKD) exhibit increased morbidity and mortality which is associated with an increased systemic inflammatory burden. Identifying and managing comorbid diseases that contribute to this load may inform novel care pathways that could have a beneficial impact on the morbidity/mortality associated with CKD. Periodontitis, a highly prevalent, chronic inflammatory disease affecting the supporting structures of teeth, is associated with an increased systemic inflammatory and oxidative stress burden and the successful treatment of periodontitis has been shown to reduce both. This pilot study aims to gather data to inform a definitive study into the impact of successful periodontal treatment on the cardio-renal health of patients with CKD. This pilot study will employ a randomised, controlled, parallel-group design. Sixty adult patients, with CKD with a high risk of progression and with periodontitis, from the Queen Elizabeth Hospital, Birmingham, will be randomised to receive either immediate, intensive periodontal treatment (n = 30) or treatment at a delay of 12 months (n = 30). Patients will be excluded if they have reached end-stage renal disease or have received specialist periodontal treatment in the previous year. Periodontal treatment will be delivered under local anaesthetic, on an outpatient basis, over several visits by a qualified dental hygienist at the Birmingham Dental Hospital, UK. Patients in the delayed-treatment arm will continue to receive the standard community level of periodontal care for a period of 12 months followed by the intensive periodontal treatment. Randomization will occur using a centralised telephone randomisation service, following baseline assessments. The assessor of periodontal health will be blinded to the patients' treatment allocation. Patients in either arm will be followed up at 3-monthly intervals for 18 months. Aside from the pilot outcomes to inform the practicalities of a larger trial later, data on cardio-renal function, periodontal health and patient-reported outcomes will be collected at each time point. This pilot randomised controlled trial will investigate the viability of undertaking a larger-scale study investigating the effect of treating periodontitis and maintaining periodontal health on cardio-renal outcomes in patients with CKD. National Institute of Health Research (NIHR) Clinical Research Network (UKCRN ID: 18458), ID: ISRCTN10227738 . Registered retrospectively to both registers on 23 April 2015.

A multicentre, randomised, controlled trial to assess the safety, ease of use, and reliability of hyaluronic acid/carboxymethylcellulose powder adhesion barrier versus no barrier in colorectal laparoscopic surgery.

PubMed

Berdah, Stéphane V; Mariette, Christophe; Denet, Christine; Panis, Yves; Laurent, Christophe; Cotte, Eddy; Huten, Nöel; Le Peillet Feuillet, Eliane; Duron, Jean-Jacques

2014-10-27

Intra-peritoneal adhesions are frequent following abdominal surgery and are the most common cause of small bowel obstructions. A hyaluronic acid/carboxymethylcellulose (HA/CMC) film adhesion barrier has been shown to reduce adhesion formation in abdominal surgery. An HA/CMC powder formulation was developed for application during laparoscopic procedures. This was an exploratory, prospective, randomised, single-blind, parallel-group, Phase IIIb, multicentre study conducted at 15 hospitals in France to assess the safety of HA/CMC powder versus no adhesion barrier following laparoscopic colorectal surgery. Subjects ≥18 years of age who were scheduled for colorectal laparoscopy (Mangram contamination class I‒III) within 8 weeks of selection were eligible, regardless of aetiology. Participants were randomised 1:1 to the HA/CMC powder or no adhesion barrier group using a centralised randomisation list. Patients assigned to HA/CMC powder received a single application of 1 to 10 g on adhesion-prone areas. In the no adhesion barrier group, no adhesion barrier or placebo was applied. The primary safety assessments were the incidence of adverse events, serious adverse events, and surgical site infections (SSIs) for 30 days following surgery. Between-group comparisons were made using Fisher's exact test. Of those randomised to the HA/CMC powder (n = 105) or no adhesion barrier (n = 104) groups, one patient in each group discontinued prior to the study end (one death in each group). Adverse events were more frequent in the HA/CMC powder group versus the no adhesion barrier group (63% vs. 39%; P <0.001), as were serious adverse events (28% vs. 11%; P <0.001). There were no statistically significant differences between the HA/CMC powder group and the no adhesion barrier group in SSIs (21% vs. 14%; P = 0.216) and serious SSIs (12% vs. 9%; P = 0.38), or in the most frequent serious SSIs of pelvic abscess (5% and 2%; significance not tested), anastomotic fistula (3% and 4%), and peritonitis (2% and 3%). This exploratory study found significantly higher rates of adverse events and serious adverse events in the HA/CMC powder group compared with the no adhesion barrier group in laparoscopic colorectal resection. ClinicalTrials.gov NCT00813397. Registered 19 December 2008.

‘Putting Life in Years’ (PLINY) telephone friendship groups research study: pilot randomised controlled trial

PubMed Central

2014-01-01

Background Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Methods Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. Results We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Conclusions Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre, and/or involve dedicated management of volunteers. Trial registration ISRCTN28645428. PMID:24758530

'Putting Life in Years' (PLINY) telephone friendship groups research study: pilot randomised controlled trial.

PubMed

Mountain, Gail A; Hind, Daniel; Gossage-Worrall, Rebecca; Walters, Stephen J; Duncan, Rosie; Newbould, Louise; Rex, Saleema; Jones, Carys; Bowling, Ann; Cattan, Mima; Cairns, Angela; Cooper, Cindy; Edwards, Rhiannon Tudor; Goyder, Elizabeth C

2014-04-24

Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre, and/or involve dedicated management of volunteers. ISRCTN28645428.

The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial.

PubMed

Dodd, Jodie M; Ahmed, Sharmina; Karnon, Jonathan; Umberger, Wendy; Deussen, Andrea R; Tran, Thach; Grivell, Rosalie M; Crowther, Caroline A; Turnbull, Deborah; McPhee, Andrew J; Wittert, Gary; Owens, Julie A; Robinson, Jeffrey S

2015-01-01

Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10(+0)-20(+0) weeks, and BMI ≥25 kg/m(2) were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group $11261.19±$14573.97 versus Standard Care Group $11306.70±$14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to $45,000. Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes. Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected attention deficit hyperactivity disorder: single-blind randomised controlled trial.

PubMed

Hollis, Chris; Hall, Charlotte L; Guo, Boliang; James, Marilyn; Boadu, Janet; Groom, Madeleine J; Brown, Nikki; Kaylor-Hughes, Catherine; Moldavsky, Maria; Valentine, Althea Z; Walker, Gemma M; Daley, David; Sayal, Kapil; Morriss, Richard

2018-04-26

Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04-2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77-0.93), increased clinicians' confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09-2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as 'cost neutral'. QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy. © 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

A randomised controlled intervention trial evaluating the efficacy of a Mediterranean dietary pattern on cognitive function and psychological wellbeing in healthy older adults: the MedLey study.

PubMed

Knight, Alissa; Bryan, Janet; Wilson, Carlene; Hodgson, Jonathan; Murphy, Karen

2015-04-28

The incidence of age-related cognitive decline is rising considerably around the world. There is evidence from a number of recent cross-sectional and prospective studies indicating positive associations between the Mediterranean dietary pattern (MedDiet) and improved cognitive outcomes among the elderly including, reduced age-related cognitive decline and enhanced age-related cognitive performance. However, to date no study has validated these associations in healthy older adult populations (≥65 years and above) with randomised evidence. The main aim of the present study is to provide justified evidence regarding the efficacy of a MedDiet approach to safely reduce the onset of cognitive decline, and promote optimal cognitive performance among healthy older adults using rigorous, randomised intervention methodology. MedLey is a 6-month, randomised controlled 2-cohort parallel group intervention trial, with initial assessment at baseline and repeated every three months. A sample of 166 healthy Australian men and women aged 65 years and above, with normal cognitive function and proficient in English language were recruited from metropolitan Adelaide, South Australia for the study. Participants randomly allocated to the experimental group are required to maintain an intervention dietary pattern based from the traditional Cretan MedDiet (i.e. vegetables, fruits, olive oil, legumes, fish, whole grain cereals, nuts and seeds and low consumption of processed foods, dairy products, red meat and vegetable oils) for six months, while those participants allocated to the control group are asked to maintain their customary lifestyle and diet. The primary outcome of interest is the quantitative difference in age-related cognitive performance, as measured by latent variables (cognitive constructs) sensitive to normal ageing and diet (i.e. speed of processing, memory, attention, executive functions, visual spatial and visuomotor ability). Secondary outcomes include change in biomarkers of inflammation, oxidative stress, lipid metabolism, glucose, insulin, blood flow velocity, and psychological well-being factors (i.e. stress, sleep, anxiety, depression). To our knowledge this will be one of the first randomised clinical trials worldwide to provide evidence for the cause-effect relationship between the MedDiet and age-related cognitive function in a healthy older adult population (≥65 years and over). Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000602729.

A randomised controlled trial to determine the clinical and cost effectiveness of thulium laser transurethral vaporesection of the prostate (ThuVARP) versus transurethral resection of the prostate (TURP) in the National Health Service (NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.

PubMed

Worthington, Jo; Taylor, Hilary; Abrams, Paul; Brookes, Sara T; Cotterill, Nikki; Noble, Sian M; Page, Tobias; Swami, K Satchi; Lane, J Athene; Hashim, Hashim

2017-04-17

Transurethral resection of the prostate (TURP) has been the standard operation for benign prostatic obstruction (BPO) for 40 years, with approximately 25,000 procedures performed annually, and has remained largely unchanged. It is generally a successful operation, but has well-documented risks for the patient. Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a surgical technique similar to TURP. The small amount of study data currently available suggests that ThuVARP may have certain advantages over TURP, including reduced blood loss and shorter hospital stay, earlier return to normal activities, and shorter duration of catheterisation. A multicentre, pragmatic, randomised, controlled, parallel-group trial of ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable for prostate surgery were randomised to receive either ThuVARP or TURP at four university teaching hospitals, and three district general hospitals. The key aim of the trial is to determine whether ThuVARP is equivalent to TURP judged on both the patient-reported International Prostate Symptom Score (IPSS) and the maximum urine flow rate (Qmax) at 12 months post-surgery. The general population has an increased life expectancy. As men get older their prostates enlarge, potentially causing BPO, which often requires surgery. Therefore, as the population ages, more prostate operations are needed to relieve obstruction. There is hence sustained interest in the condition and increasing need to find safer techniques than TURP. Various laser techniques have become available but none are widely used in the NHS because of lengthy training required for surgeons or inferior performance on clinical outcomes. Promising initial evidence from one RCT shows that ThuVARP has equivalent clinical effectiveness when compared to TURP, as well as other potential advantages. As ThuVARP uses a technique similar to that used in TURP, the learning curve is short, potentially making it also very quickly generalisable. This randomised study is designed to provide the high-quality evidence, in an NHS setting, with a range of patient-reported, clinical and cost-effectiveness outcomes, which will underpin and inform future NICE guidance. ISRCTN registry, ISRCTN00788389 . Registered on 20 September 2013.

Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial.

PubMed

McKenzie, Joanne E; French, Simon D; O'Connor, Denise A; Mortimer, Duncan S; Browning, Colette J; Russell, Grant M; Grimshaw, Jeremy M; Eccles, Martin P; Francis, Jill J; Michie, Susan; Murphy, Kerry; Kossenas, Fiona; Green, Sally E

2013-08-19

Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers. This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs' (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial). The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs' detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation. Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011).

Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial.

PubMed

Peters, Mark J; Jones, Gareth A L; Wiley, Daisy; Wulff, Jerome; Ramnarayan, Padmanabhan; Ray, Samiran; Inwald, David; Grocott, Michael; Griksaitis, Michael; Pappachan, John; O'Neill, Lauran; Eaton, Simon; Mouncey, Paul R; Harrison, David A; Rowan, Kathryn M

2018-06-04

Oxygen saturation monitoring for children receiving respiratory support is standard worldwide. No randomised clinical trials have compared peripheral oxygen saturation (SpO 2 ) targets for critically ill children. The harm of interventions to raise SpO 2 to > 94% may exceed their benefits. We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and < 16 years of age receiving invasive or non-invasive respiratory support and supplemental oxygen who were admitted urgently to one of three paediatric intensive care units. A 'research without prior consent' approach was employed. Children were randomly assigned to a liberal oxygenation group (SpO 2 targets > 94%) or a conservative oxygenation group (SpO 2  = 88-92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO 2 and safety. The Oxy-PICU trial was registered before recruitment: ClinicalTrials.gov identifier NCT03040570. A total of 159 children met the inclusion criteria, of whom 119 (75%) were randomised between April and July 2017, representing a rate of 10 patients per month per site. The mean time to randomisation from first contact with an intensive care team was 1.9 (SD 2.2) h. Consent to continue in the study was obtained in 107 cases (90%); the children's parents/legal representatives were supportive of the consent process. The median (interquartile range, IQR) of time-weighted individual mean SpO 2 was 94.9% (92.6-97.1) in the conservative oxygenation group and 97.5% (96.2-98.4) in the liberal group [difference 2.7%, 95% confidence interval (95% CI) 1.3-4.0%, p < 0.001]. Median (IQR) time-weighted individual mean FiO 2 was 0.28 (0.24-0.37) in the conservative group and 0.37 (0.30-0.42) in the liberal group (difference 0.08, 95% CI 0.03-0.13, p < 0.001). There were no significant between-group differences in length of stay, duration of organ support or mortality. Two prespecified serious adverse events (cardiac arrests) occurred, both in the liberal oxygenation group. A definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children.

United Kingdom Frozen Shoulder Trial (UK FROST), multi-centre, randomised, 12 month, parallel group, superiority study to compare the clinical and cost-effectiveness of Early Structured Physiotherapy versus manipulation under anaesthesia versus arthroscopic capsular release for patients referred to secondary care with a primary frozen shoulder: study protocol for a randomised controlled trial.

PubMed

Brealey, Stephen; Armstrong, Alison L; Brooksbank, Andrew; Carr, Andrew Jonathan; Charalambous, Charalambos P; Cooper, Cushla; Corbacho, Belen; Dias, Joseph; Donnelly, Iona; Goodchild, Lorna; Hewitt, Catherine; Keding, Ada; Kottam, Lucksy; Lamb, Sarah E; McDaid, Catriona; Northgraves, Matthew; Richardson, Gerry; Rodgers, Sara; Shah, Sarwat; Sharp, Emma; Spencer, Sally; Torgerson, David; Toye, Francine; Rangan, Amar

2017-12-22

Frozen shoulder (also known as adhesive capsulitis) occurs when the capsule, or the soft tissue envelope around the ball and socket shoulder joint, becomes scarred and contracted, making the shoulder tight, painful and stiff. It affects around 1 in 12 men and 1 in 10 women of working age. Although this condition can settle with time (typically taking 1 to 3 years), for some people it causes severe symptoms and needs referral to hospital. Our aim is to evaluate the clinical and cost-effectiveness of two invasive and costly surgical interventions that are commonly used in secondary care in the National Health Service (NHS) compared with a non-surgical comparator of Early Structured Physiotherapy. We will conduct a randomised controlled trial (RCT) of 500 adult patients with a clinical diagnosis of frozen shoulder, and who have radiographs that exclude other pathology. Early Structured Physiotherapy with an intra-articular steroid injection will be compared with manipulation under anaesthesia with a steroid injection or arthroscopic (keyhole) capsular release followed by manipulation. Both surgical interventions will be followed with a programme of post-procedural physiotherapy. These treatments will be undertaken in NHS hospitals across the United Kingdom. The primary outcome and endpoint will be the Oxford Shoulder Score (a patient self-reported assessment of shoulder function) at 12 months. This will also be measured at baseline, 3 and 6 months after randomisation; and on the day that treatment starts and 6 months later. Secondary outcomes include the Disabilities of Arm Shoulder and Hand (QuickDASH) score, the EQ-5D-5 L score, pain, extent of recovery and complications. We will explore the acceptability of the different treatments to patients and health care professionals using qualitative methods. The three treatments being compared are the most frequently used in secondary care in the NHS, but there is uncertainty about which one works best and at what cost. UK FROST is a rigorously designed and adequately powered study to inform clinical decisions for the treatment of this common condition in adults. International Standard Randomised Controlled Trial Register, ID: ISRCTN48804508 . Registered on 25 July 2014.

GestationaL Obesity Weight management: Implementation of National Guidelines (GLOWING): a pilot cluster randomised controlled trial of a guideline implementation intervention for the management of maternal obesity by midwives.

PubMed

Heslehurst, Nicola; Rankin, Judith; McParlin, Catherine; Sniehotta, Falko F; Howel, Denise; Rice, Stephen; McColl, Elaine

2018-01-01

Weight management in pregnancy guidelines exist, although dissemination alone is an ineffective means of implementation. Midwives identify the need for support to overcome complex barriers to practice. An evaluation of an intervention to support midwives' guideline implementation would require a large-scale cluster randomised controlled trial. A pilot study is necessary to explore the feasibility of delivery and evaluation prior to a definitive trial. The GestationaL Obesity Weight management: Implementation of National Guidelines (GLOWING) trial aims to test whether it is feasible and acceptable to deliver a behaviour change intervention to support midwives' implementation of weight management guidelines. GLOWING is a multi-centre parallel group pilot cluster randomised controlled trial comparing the delivery of a behaviour change intervention for midwives versus usual practice. Four NHS Trusts (clusters) will be randomised to intervention and control arms, stratified by size of maternity services. The intervention uses social cognitive theory and consists of face-to-face midwifery training plus information resources for routine practice. The main outcomes are whether the intervention and trial procedures are feasible and acceptable to participants and the feasibility of recruitment and data collection for a definitive trial. Target recruitment involves all eligible midwives in the intervention arm recruited to receive the intervention, 30 midwives and pregnant women per arm for baseline and outcome questionnaire data collection and 20 midwives and women to provide qualitative data. All quantitative and qualitative analyses will be descriptive with the purpose of informing the development of the definitive trial. This pilot study has been developed to support community midwives' implementation of guidelines. Community midwives have been selected as they usually carry out the booking appointment which includes measuring and discussing maternal body mass index. A cluster design is the gold standard in implementation research as there would be a high risk of contamination if randomisation was at individual midwife level: community midwives usually work in locality-based teams, interact on a daily basis, and share care of pregnant women. The results of the pilot trial will be used to further develop and refine GLOWING prior to a definitive trial to evaluate effectiveness and cost-effectiveness. ISRCTN46869894; retrospectively registered 25th May 2016.

Double-label immunofluorescence method for simultaneous detection of adenovirus and herpes simplex virus from the eye.

PubMed

Walpita, P; Darougar, S

1989-07-01

The development and application of a double-label immunofluorescence method which has the potential to screen for single or dual infections from any site, in single shell vial cultures, is described. In this study, a total of 1,141 ocular specimens were inoculated in shell vials, centrifuged at 15,000 X g for 1 h, incubated at 37 degrees C for 48 h, and fixed in methanol at room temperature for 15 min. The virus inclusions were detected by staining with a double-label indirect immunofluorescence procedure using mixtures of appropriate first antibodies, followed by fluorescein- and rhodamine-conjugated second antibodies. Each specimen was also inoculated in parallel by the conventional virus isolation method. The sensitivity and specificity of the double-label shell vial procedure were comparable to those with the conventional method, and the former test took only 48 h to complete. The test offers a rapid and simple single-vial procedure which allows for individual or simultaneous detection of multiple pathogens. It results in savings in time and cost over the conventional virus isolation method and other shell vial procedures.

Nucleic acid detection methods

DOEpatents

Smith, C.L.; Yaar, R.; Szafranski, P.; Cantor, C.R.

1998-05-19

The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3{prime}-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated. 18 figs.

Results from a blind and a non-blind randomised trial run in parallel: experience from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial.

PubMed

Veerus, Piret; Fischer, Krista; Hakama, Matti; Hemminki, Elina

2012-04-04

The Estonian Postmenopausal Hormone Therapy (EPHT) Trial assigned 4170 potential participants prior to recruitment to blind or non-blind hormone therapy (HT), with placebo or non-treatment the respective alternatives. Before having to decide on participation, women were told whether they had been randomised to the blind or non-blind trial. Eligible women who were still willing to join the trial were recruited. After recruitment participants in the non-blind trial (N = 1001) received open-label HT or no treatment, participants in the blind trial (N = 777) remained blinded until the end of the trial. The aim of this paper is to analyse the effect of blinding on internal and external validity of trial outcomes. Effect of blinding was calculated as the hazard ratio of selected chronic diseases, total mortality and all outcomes. For analysing the effect of blinding on external validity, the hazard ratios from women recruited to the placebo arm and to the non-treatment arm were compared with those not recruited; for analysing the effect of blinding on internal validity, the hazard ratios from the blind trial were compared with those from the non-blind trial. The women recruited to the placebo arm had less cerebrovascular disease events (HR 0.43; 95% CI: 0.26-0.71) and all outcomes combined (HR 0.76; 95% CI: 0.63-0.91) than those who were not recruited. Among women recruited or not recruited to the non-treatment arm, no differences were observed for any of the outcomes studied.Among women recruited to the trial, the risk for coronary heart disease events (HR 0.77; 95% CI: 0.64-0.93), cerebrovascular disease events (HR 0.66; 95%CI: 0.47-0.92), and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94) was smaller among participants in the blind trial than in the non-blind trial. There was no difference between the blind and the non-blind trial for total cancer (HR 0.95; 95% CI: 0.64-1.42), bone fractures (0.93; 95% CI: 0.74-1.16), and total mortality (HR 1.03; 95% CI: 0.53-1.98). The results from blind and non-blind trials may differ, even if the target population is the same. Blinding may influence both internal and external validity. The effect of blinding may vary for different outcome events. [ISRCTN35338757].

Evaluation of wet-cupping therapy for persistent non-specific low back pain: a randomised, waiting-list controlled, open-label, parallel-group pilot trial.

PubMed

Kim, Jong-In; Kim, Tae-Hun; Lee, Myeong Soo; Kang, Jung Won; Kim, Kun Hyung; Choi, Jun-Yong; Kang, Kyung-Won; Kim, Ae-Ran; Shin, Mi-Suk; Jung, So-Young; Choi, Sun-mi

2011-06-10

Persistent non-specific low back pain (PNSLBP) is one of the most frequently experienced types of back pain around the world. Wet-cupping is a common intervention for various pain conditions, especially in Korea. In this context, we conducted a pilot study to determine the effectiveness and safety of wet-cupping treatment for PNSLBP. We recruited 32 participants (21 in the wet-cupping group and 11 in the waiting-list group) who had been having PNSLBP for at least 3 months. The participants were recruited at the clinical research centre of the Korea Institute of Oriental Medicine, Korea. Eligible participants were randomly allocated to wet-cupping and waiting-list groups. Following the practice of traditional Korean medicine, the treatment group was provided with wet-cupping treatment at two acupuncture points among the BL23, BL24 and BL25 6 times within 2 weeks. Usual care, including providing brochures for exercise, general advice for PNSLBP and acetaminophen, was allowed in both groups. Separate assessors participated in the outcome assessment. We used the 0 to 100 numerical rating scale (NRS) for pain, the McGill Pain Questionnaire for pain intensity (PPI) and the Oswestry Disability Questionnaire (ODQ), and we assessed acetaminophen use and safety issues. The results showed that the NRS score for pain decreased (-16.0 [95% CI: -24.4 to -7.7] in the wet-cupping group and -9.1 [-18.1 to -0.1] in the waiting-list group), but there was no statistical difference between the groups (p = 0.52). However, the PPI scores showed significant differences between the two groups (-1.2 [-1.6 to -0.8] for the wet-cupping group and -0.2 [-0.8 to 0.4] for the waiting-list group, p < 0.01). In addition, less acetaminophen was used in the wet-cupping group during 4 weeks (p = 0.09). The ODQ score did not show significant differences between the two groups (-5.60 [-8.90 to -2.30] in the wet-cupping group and -1.8 [-5.8 to 2.2] in the waiting-list group, p = 0.14). There was no report of adverse events due to wet-cupping. This pilot study may provide preliminary data on the effectiveness and safety of wet-cupping treatments for PNSLBP. Future full-scale randomised controlled trials will be needed to provide firm evidence of the effectiveness of this intervention.

"Passive victim – strong survivor"? Perceived meaning of labels applied to women who were raped

PubMed Central

Papendick, Michael

2017-01-01

Three experiments (total N = 464) were conducted in parallel with English- and German-speaking participants to examine the perceived meanings and effects of the labels "victim" versus "survivor" (and their German equivalents) when applied to a woman who was raped. In Study 1 (N = 179), participants read a rape vignette and then rated the meaning of the label it contained (either "victim" or "survivor") on a 15-item semantic differential. Independent of language and participant gender, "survivor" was perceived more positively overall (e.g., as strong, brave, active) than was "victim" (weak, passive, but also innocent). In Study 2 (N = 95), labels were varied within items assessing judgments of an acquaintance-rape case (e.g., "Does the victim [survivor] … carry a certain responsibility for what happened?"), focusing on short-term outcomes. Significant interaction effects of label and participants’ gender emerged on case-related judgments. Participants in both language samples judged "survivor" to be a less appropriate term than "victim". In Study 3 (N = 190), participants read a text in which a woman who had been raped labeled herself as either "victim" or "survivor", focusing on the coping with sexual violence. As in Study 2, German-language participants showed no significant effects of the label on their case judgments but rejected the term "survivor" as inappropriate; English-language participants, by contrast, perceived the woman describing herself as "survivor" to be more psychologically stable and regarded the use of both labels as appropriate. Results are discussed in terms of their applied relevance for communicating about sexual violence. PMID:28493976

Colour correct: the interactive effects of food label nutrition colouring schemes and food category healthiness on health perceptions.

PubMed

Nyilasy, Gergely; Lei, Jing; Nagpal, Anish; Tan, Joseph

2016-08-01

The purpose of the present study was to examine the effects of food label nutrition colouring schemes in interaction with food category healthiness on consumers' perceptions of food healthiness. Three streams of colour theory (colour attention, colour association and colour approach-avoidance) in interaction with heuristic processing theory provide consonant predictions and explanations for the underlying psychological processes. A 2 (food category healthiness: healthy v. unhealthy)×3 (food label nutrient colouring schemes: healthy=green, unhealthy=red (HGUR) v. healthy=red, unhealthy=green (HRUG) v. no colour (control)) between-subjects design was used. The research setting was a randomised-controlled experiment using varying formats of food packages and nutritional information colouring. Respondents (n 196) sourced from a national consumer panel, USA. The findings suggest that, for healthy foods, the nutritional colouring schemes reduced perceived healthiness, irrespective of which nutrients were coloured red or green (healthinesscontrol=4·86; healthinessHGUR=4·10; healthinessHRUG=3·70). In contrast, for unhealthy foods, there was no significant difference in perceptions of food healthiness when comparing different colouring schemes against the control. The results make an important qualification to the common belief that colour coding can enhance the correct interpretation of nutrition information and suggest that this incentive may not necessarily support healthier food choices in all situations.

An open-label six-month extension study to investigate the safety and efficacy of an extract of Artemisia annua for managing pain, stiffness and functional limitation associated with osteoarthritis of the hip and knee.

PubMed

Hunt, Sheena; Stebbings, Simon; McNamara, Debra

2016-10-28

This six-month single-centre open-label extension study, conducted at the University of Otago, Dunedin, follows from a previously published 12-week pilot double-blind randomised placebo-controlled study of dietary supplement, Arthrem® (ART) in patients with osteoarthritis (OA) of the hip or knee. The pilot double-blind study showed that treatment with ART 150 mg twice-daily was associated with clinically relevant pain reduction. The extension study aims were to assess longer-term safety and efficacy during six months' treatment following the pilot trial. Patients who completed the pilot double-blind study had the option to continue on open-label treatment with ART for a further six months. Safety was assessed by adverse event monitoring and laboratory tests at three and six months. Efficacy was assessed at three and six months using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®). Thirty-four patients entered the optional extension and 28 completed six months' treatment. ART was well tolerated when taken for up to nine months. Improvements in WOMAC® efficacy parameters reported in the double-blind phase of the study were maintained over six months. ART appears to be a safe and effective alternative for managing the symptoms of OA over an extended period.

Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial.

PubMed

Ueki, Kohjiro; Sasako, Takayoshi; Okazaki, Yukiko; Kato, Masayuki; Okahata, Sumie; Katsuyama, Hisayuki; Haraguchi, Mikiko; Morita, Ai; Ohashi, Ken; Hara, Kazuo; Morise, Atsushi; Izumi, Kazuo; Ishizuka, Naoki; Ohashi, Yasuo; Noda, Mitsuhiko; Kadowaki, Takashi

2017-12-01

Limited evidence suggests that multifactorial interventions for control of glucose, blood pressure, and lipids reduce macrovascular complications and mortality in patients with type 2 diabetes. However, safe and effective treatment targets for these risk factors have not been determined for such interventions. In this multicentre, open-label, randomised, parallel-group trial, undertaken at 81 clinical sites in Japan, we randomly assigned (1:1) patients with type 2 diabetes aged 45-69 years with hypertension, dyslipidaemia, or both, and an HbA 1c of 6·9% (52·0 mmol/mol) or higher, to receive conventional therapy for glucose, blood pressure, and lipid control (targets: HbA 1c <6·9% [52·0 mmol/mol], blood pressure <130/80 mm Hg, LDL cholesterol <120 mg/dL [or 100 mg/dL in patients with a history of coronary artery disease]) or intensive therapy (HbA 1c <6·2% [44·3 mmol/mol], blood pressure <120/75 mm Hg, LDL cholesterol <80 mg/dL [or 70 mg/dL in patients with a history of coronary artery disease]). Randomisation was done using a computer-generated, dynamic balancing method, stratified by sex, age, HbA 1c , and history of cardiovascular disease. Neither patients nor investigators were masked to group assignment. The primary outcome was occurrence of any of a composite of myocardial infarction, stroke, revascularisation (coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting), and all-cause mortality. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00300976. Between June 16, 2006, and March 31, 2009, 2542 eligible patients were randomly assigned to intensive therapy or conventional therapy (1271 in each group) and followed up for a median of 8·5 years (IQR 7·3-9·0). Two patients in the intensive therapy group were found to be ineligible after randomisation and were excluded from the analyses. During the intervention period, mean HbA 1c , systolic blood pressure, diastolic blood pressure, and LDL cholesterol concentrations were significantly lower in the intensive therapy group than in the conventional therapy group (6·8% [51·0 mmol/mol] vs 7·2% [55·2 mmol/mol]; 123 mm Hg vs 129 mm Hg; 71 mm Hg vs 74 mm Hg; and 85 mg/dL vs 104 mg/dL, respectively; all p<0·0001). The primary outcome occurred in 109 patients in the intensive therapy group and in 133 patients in the conventional therapy group (hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·094). In a post-hoc breakdown of the composite outcome, frequencies of all-cause mortality (HR 1·01, 95% CI 0·68-1·51; p=0·95) and coronary events (myocardial infarction, coronary artery bypass surgery, and percutaneous transluminal coronary angioplasty; HR 0·86, 0·58-1·27; p=0·44) did not differ between groups, but cerebrovascular events (stroke, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting) were significantly less frequent in the intensive therapy group (HR 0·42, 0·24-0·74; p=0·002). Apart from non-severe hypoglycaemia (521 [41%] patients in the intensive therapy group vs 283 [22%] in the conventional therapy group, p<0·0001) and oedema (193 [15%] vs 129 [10%], p=0·0001), the frequencies of major adverse events did not differ between groups. Our results do not fully support the efficacy of further intensified multifactorial intervention compared with current standard care for the prevention of a composite of coronary events, cerebrovascular events, and all-cause mortality. Nevertheless, our findings suggest a potential benefit of an intensified intervention for the prevention of cerebrovascular events in patients with type 2 diabetes. Ministry of Health, Labour and Welfare of Japan, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Kissei Pharmaceutical, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Novo Nordisk, Ono Pharmaceutical, Pfizer, Sanwa Kagaku Kenkyusho, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation-frequency encoded multi-color fluorescent DNA analysis in an optofluidic chip.

PubMed

Dongre, Chaitanya; van Weerd, Jasper; Besselink, Geert A J; Vazquez, Rebeca Martinez; Osellame, Roberto; Cerullo, Giulio; van Weeghel, Rob; van den Vlekkert, Hans H; Hoekstra, Hugo J W M; Pollnau, Markus

2011-02-21

We introduce a principle of parallel optical processing to an optofluidic lab-on-a-chip. During electrophoretic separation, the ultra-low limit of detection achieved with our set-up allows us to record fluorescence from covalently end-labeled DNA molecules. Different sets of exclusively color-labeled DNA fragments-otherwise rendered indistinguishable by spatio-temporal coincidence-are traced back to their origin by modulation-frequency-encoded multi-wavelength laser excitation, fluorescence detection with a single ultrasensitive, albeit color-blind photomultiplier, and Fourier analysis decoding. As a proof of principle, fragments obtained by multiplex ligation-dependent probe amplification from independent human genomic segments, associated with genetic predispositions to breast cancer and anemia, are simultaneously analyzed.

Rationale and design of the SMaRT trial: A randomised, prospective, parallel, non-blinded, one-centre trial to evaluate the use of magnetic resonance imaging in acute setting in patients presenting with suspected scaphoid fracture.

PubMed

Rua, Tiago; Vijayanathan, Sanjay; Parkin, David; Goh, Vicky; McCrone, Paul; Gidwani, Sam

2018-04-01

Background Wrist injury is a common presentation to the Emergency Department in the United Kingdom. Among these injuries, the scaphoid is the most common fractured carpal bone. However, given the limited ability of conventional radiography to accurately diagnose a suspected scaphoid fracture on presentation, its diagnosis and management remain challenging. Despite the vast clinical evidence supporting the superior accuracy of magnetic resonance imaging, there is little to no evidence around the real-world clinical and economic impact of immediate magnetic resonance imaging in the management of suspected scaphoid fractures. Methods Review of design and implementation challenges associated with the identification and subsequent recruitment of eligible patients, implementation of a novel clinical pathway in an acute setting, rationale behind the primary and secondary outcomes selected and measurement of the primary outcome. Results The Scaphoid Magnetic Resonance Imaging in Trauma trial is a single-site prospective, randomised, non-blinded, parallel design trial that aims to evaluate the use of immediate magnetic resonance imaging in the management of patients presenting to the acute setting with suspected scaphoid fractures. The primary outcome is the total 3-month cost per patient associated with the diagnosis and treatment of suspected scaphoid fractures. It is hypothesised that the immediate use of magnetic resonance imaging, a more accurate but expensive imaging modality, in patients with negative findings in the initial four-view radiography, will reduce the overall National Health Service costs by promoting definitive care and avoiding unnecessary diagnostic and treatment procedures. Other rationale design considerations in the recruitment, randomisation, data acquisition and intervention implementation are also discussed. Several of these challenges derive from real-world operational issues associated with the provision of magnetic resonance imaging in an intrinsically complex acute setting. Staff engagement during the trial's planning phase, combined with an extensive training programme rolled out prior to the trial's launch, were essential to raise staff awareness and engagement. Given the acute nature of the clinical condition, the latter was deemed essential as the eligibility assessment, recruitment, randomisation and treatment allocation processes all need to happen in a very tight time frame. Limitations Findings from the Scaphoid Magnetic Resonance Imaging in Trauma trial might not be generalisable to other National Health Service hospitals, foreign healthcare systems nor patient presentations outside normal magnetic resonance imaging working hours. Conclusion The Scaphoid Magnetic Resonance Imaging in Trauma trial was designed to evaluate the costs, patient satisfaction and clinical outcomes around the management of suspected scaphoid fractures and ultimately provide solid evidence on which to base the United Kingdom and international clinical practice. This article discusses the steps considered in the design of this novel trial, with particular emphasis on the issues and lessons learned during the planning and implementation stages.

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial.

PubMed

Anderson, Ian M; Blamire, Andrew; Branton, Tim; Clark, Ross; Downey, Darragh; Dunn, Graham; Easton, Andrew; Elliott, Rebecca; Elwell, Clare; Hayden, Katherine; Holland, Fiona; Karim, Salman; Loo, Colleen; Lowe, Jo; Nair, Rajesh; Oakley, Timothy; Prakash, Antony; Sharma, Parveen K; Williams, Stephen R; McAllister-Williams, R Hamish

2017-05-01

The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine. In this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study. Patients were randomly assigned (1:1) to ketamine (0·5 mg/kg intravenous bolus) or saline adjunctive to the anaesthetic for the duration of their ECT course. Patients and assessment and ECT treatment teams were masked to treatment allocation, although anaesthetists administering the study medication were not. We analysed the primary outcome, Hopkins Verbal Learning Test-Revised delayed verbal recall (HVLT-R-DR) after four ECT treatments, using a Gaussian repeated measures model in all patients receiving the first ECT treatment. In the same population, safety was assessed by adverse effect monitoring. This trial was registered with International Standard Randomised Controlled Trial Number, number ISRCTN14689382. Between early December, 2012, and mid-June, 2015, 628 patients were screened for eligibility, of whom 79 were randomly assigned to treatment (40 in the ketamine group vs 39 in the saline group). Ketamine (mean 5·17, SD 2·92), when compared with saline (5·54, 3·42), had no benefit on the primary outcome (HVLT-R-DR; difference in means -0·43 [95% CI -1·73 to 0·87]). 15 (45%) of 33 ketamine-treated patients compared with 10 (27%) of 37 patients receiving saline experienced at least one adverse event which included two (6%) of 33 patients who had ketamine-attributable transient psychological effects. Psychiatric adverse events were the most common in both groups (six [27%] of 22 adverse events in the ketamine group vs seven [54%] of 13 in the saline group). No evidence of benefit for ketamine was found although the sample size used was small; however, the results excluded greater than a small to moderate benefit with 95% confidence. The results do not support the use of adjunctive low-dose ketamine in routine ECT treatment. National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus

PubMed Central

2014-01-01

Background Diabetes mellitus may be present in patients with cystic fibrosis starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in cystic fibrosis, cystic fibrosis related diabetes will be diagnosed more frequently in the future. Up to date, no data are available to answer the question if cystic fibrosis related diabetes should always initially be treated by insulin therapy. Missing data regarding oral antidiabetic treatment of newly diagnosed cystic fibrosis related diabetes are an important reason to recommend insulin treatment. Several centres report the successful management of cystic fibrosis related diabetes using oral anti-diabetic drugs at least for some years. Oral therapies would be less invasive for a patient group which is highly traumatized by a very demanding therapy. Based on an initiative of the German Mukoviszidosis-Foundation, the present study tries to answer the question, whether oral therapy with repaglinide is as effective as insulin therapy in cystic fibrosis patients with early diagnosed diabetes mellitus. Methods/Design In all cystic fibrosis patients with an age of 10 years or older, an oral glucose tolerance test is recommended. The result of this test is classified according to the WHO cut off values. It is required to have two diabetes positive oral glucose tolerance tests for the diagnosis of diabetes mellitus. This study is a multi-national, multicentre, open labelled, randomized and prospective controlled parallel group’s trial, with 24 months treatment. The primary objective of this trial is to compare the glycaemic control of oral therapy with Repaglinide with insulin injections in patients with cystic fibrosis related diabetes after 2 years of treatment. The trial should include 74 subjects showing cystic fibrosis related diabetes newly diagnosed by oral glucose tolerance test during annual screening for cystic fibrosis related diabetes. Patients are randomised by central fax randomisation. Primary endpoint is mean HbA1c after 24 months of treatment. Secondary endpoints are change in FEV1% predicted and change in BMI-Z-score. Discussion There is only one prospective study comparing oral antidiabetic drugs to insulin in the treatment of CFRD without fasting hyperglycaemia. The results regarding BMI after 6 months and 12 months showed an improvement for the insulin treated patients and were inconsistent for those treated with repaglinide. HbA1c and lung function (FEV1%pred) were unchanged for either group. The authors compared the changes -12 months to baseline and baseline to +12 months separately for each group. Therefore a direct comparison of the effect of repaglinide versus insulin on BMI, HbA1c and FEV1%pred was not presented. According to our protocol, we will directly compare treatment effects (HbA1c, BMI, FEV1%pred) in between both groups. The actual Cochrane report regarding “Insulin and oral agents for managing CFRD” stated that further studies are needed to establish whether there is clear benefit for hypoglycemic agents. We expect that the results of our study will help to address this clinical need. Trial registration ClinicalTrials.gov Identifier: NCT00662714 PMID:24620855

Design and methods of CYCLE-HD: improving cardiovascular health in patients with end stage renal disease using a structured programme of exercise: a randomised control trial.

PubMed

Graham-Brown, M P M; March, D S; Churchward, D R; Young, H M L; Dungey, M; Lloyd, S; Brunskill, N J; Smith, A C; McCann, G P; Burton, J O

2016-07-08

There is emerging evidence that exercise training could positively impact several of the cardiovascular risk factors associated with sudden cardiac death amongst patients on haemodialysis. The primary aim of this study is to evaluate the effect of an intradialytic exercise programme on left ventricular mass. Prospective, randomised cluster open-label blinded endpoint clinical trial in 130 patients with end stage renal disease on haemodialysis. Patients will be randomised 1:1 to either 1) minimum of 30 min continuous cycling thrice weekly during dialysis or 2) standard care. The primary outcome is change in left ventricular mass at 6 months, assessed by cardiac MRI (CMR). In order to detect a difference in LV mass of 15 g between groups at 80 % power, a sample size of 65 patients per group is required. Secondary outcome measures include abnormalities of cardiac rhythm, left ventricular volumes and ejection fraction, physical function measures, anthropometric measures, quality of life and markers of inflammation, with interim assessment for some measures at 3 months. This study will test the hypothesis that an intradialytic programme of exercise leads to a regression in left ventricular mass, an important non-traditional cardiovascular risk factor in end stage renal disease. For the first time this will be assessed using CMR. We will also evaluate the efficacy, feasibility and safety of an intradialytic exercise programme using a number of secondary end-points. We anticipate that a positive outcome will lead to both an increased patient uptake into established intradialytic programmes and the development of new programmes nationally and internationally. ISRCTN11299707 (registration date 5(th) March 2015).

Protocol for a randomised controlled trial of VAsopressin versus Noradrenaline as Initial therapy in Septic sHock (VANISH)

PubMed Central

Gordon, Anthony C; Mason, Alexina J; Perkins, Gavin D; Ashby, Deborah; Brett, Stephen J

2014-01-01

Introduction Vasopressin is an alternative vasopressor in the management of septic shock. It spares catecholamine use but whether it improves outcome remains uncertain. Current evidence suggests that it may be most effective if used early and possibly in conjunction with corticosteroids. This trial will compare vasopressin to noradrenaline as initial vasopressor in the management of adult septic shock and investigate whether there is an interaction of vasopressin with corticosteroids. Methods and analysis This is a multicentre, factorial (2×2), randomised, double-blind, placebo-controlled trial. 412 patients will be recruited from multiple UK intensive care units and randomised to receive vasopressin (0–0.06 U/min) or noradrenaline (0–12 µg/min) as a continuous intravenous infusion as initial vasopressor therapy. If maximum infusion rates of this first study drug are reached, the patient will be treated with either hydrocortisone (initially 50 mg intravenous bolus six-hourly) or placebo, before additional open-label catecholamine vasopressors are prescribed. The primary outcome of the trial will be the difference in renal failure-free days between treatment groups. Secondary outcomes include need for renal replacement therapy, survival rates, other organ failures and resource utilisation. Ethics and dissemination The trial protocol and information sheets have received a favourable opinion from the Oxford A Research Ethics Committee (12/SC/0014). There is an independent Data Monitoring and Ethics Committee and independent membership of the Trial Steering Committee including patient and public involvement. The trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. Trial registration number: ISRCTN 20769191 and EudraCT 2011-005363-24. PMID:24993769

Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.

PubMed

Nishimura, Junichi; Satoh, Taroh; Fukunaga, Mutsumi; Takemoto, Hiroyoshi; Nakata, Ken; Ide, Yoshihito; Fukuzaki, Takayuki; Kudo, Toshihiro; Miyake, Yasuhiro; Yasui, Masayoshi; Morita, Shunji; Sakai, Daisuke; Uemura, Mamoru; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ohno, Yuko; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Nezu, Riichiro; Doki, Yuichiro; Mori, Masaki

2015-07-01

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oral health-related quality of life in patients with non-metal clasp dentures: a randomised cross-over trial.

PubMed

Fueki, K; Yoshida-Kohno, E; Wakabayashi, N

2017-05-01

We investigated the efficacy of non-metal clasp dentures (NMCDs) with regard to the oral health-related quality of life (OHRQoL) and compare the findings with those for conventional metal clasp-retained dentures (MCDs). This single-centre, randomised controlled, two-phase, open label, cross-over trial included 28 partially dentate individuals. The patients were randomised to receive MCDs followed by NMCDs, or the opposite sequence (n = 14 in each group); each denture was worn for 3 months. OHRQoL was evaluated using the Oral Health Impact Profile-Japanese version (OHIP-J) at entry (T-entry; before treatment with the first denture) and at 3 months after treatment with each denture (T3). An examiner evaluated denture stability, oral appearance and surface roughness before denture delivery (T0) and at T3 and denture hygiene at T3. A total of 24 patients completed the trial. There were no complications related to the dentures, abutment teeth or denture-bearing mucosa during the follow-up periods for both dentures. The mean OHIP summary score was lower for NMCDs than for MCDs, and the difference (9 points) was greater than the minimal important difference (6 points), indicating the difference was clinically relevant. The effect size was medium (0·70). Statistical analyses with linear mixed models found a significant effect of the denture type on the OHIP summary score and scores for the Oro-facial appearance, Oro-facial pain and Psychological impact domains (NMCD < MCD; P < 0·05). The results of our study suggest that NMCDs allow for better OHRQoL compared with MCDs. © 2017 John Wiley & Sons Ltd.

The short-term effect of atorvastatin plus ezetimibe therapy versus atorvastatin monotherapy on clinical outcome in acute coronary syndrome patients by gender.

PubMed

Japaridze, Lasha; Sadunishvili, Maia

2017-01-01

Atorvastatin reduces low-density lipoprotein cholesterol (LDL-C) levels and the risk of cardiovascular events, but whether the addition of ezetimibe (EZE), a non-statin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further, and if there any sex differences, is not known. To evaluate the effects of atorvastatin and EZE combination in acute coronary syndrome (ACS) patients on the incidence of composite endpoint in short-term follow-up and to assess differences according their gender. We conducted a 16-week, single-centre, prospective, randomised, open-label clinical trial involving 323 patients who had been hospitalised for an ACS within the preceding 14 days. They received atorvastatin 20 mg for 28 days, and after that 292 patients who had LDL-C levels ≥ 1.81 mmol/L were randomised to EZE 10 mg/day co-administered with atorvastatin therapy (EZE + statin) or double their current atorvastatin dose. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalisation, coronary revascularisation (≥ 30 days after randomisation), or nonfatal stroke. The Kaplan-Meier event-free survival rate at 16 weeks was 88.1% in the EZE + statin group patients and 77.0% in the atorvastatin monotherapy group (absolute risk reduction: 11.1 percentage points; hazard ratio: 2.099; 95% confidence interval: 1.165-3.781; p = 0.014). The log rank test indicated that there was not a statistically significant difference between male and female survival rates in both treatment groups (p = 0.897). The results of our study demonstrated that when added to statin therapy, EZE resulted in improved cardiovascular outcomes, and the response to atorvastatin and EZE combination was similar for both men and women.

The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial

PubMed Central

Neubert, Antje; Baarslag, Manuel Alberto; van Dijk, Monique; van Rosmalen, Joost; Standing, Joseph F; Sheng, Yucheng; Rascher, Wolfgang; Roberts, Deborah; Winslade, Jackie; Rawcliffe, Louise; Hanning, Sara M; Metsvaht, Tuuli; Giannuzzi, Viviana; Larsson, Peter; Pokorná, Pavla; Simonetti, Alessandra; Tibboel, Dick

2017-01-01

Introduction Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation. Methods and analysis The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points. Ethics Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. Trial Registration EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; pre-results. PMID:28637741

A randomised trial of a contraceptive vaginal ring in women at risk of HIV infection in Rwanda: Safety of intermittent and continuous use

PubMed Central

Van Nuil, Jennifer Ilo; Uwineza, Mireille; Umulisa, Marie Michelle; Mwambarangwe, Lambert; Ndagijimana, Jean Claude; De Baetselier, Irith; Buyze, Jozefien; Delvaux, Thérèse; Crucitti, Tania; Jespers, Vicky

2018-01-01

Background Contraceptive vaginal rings could play a role in expanding the contraceptive method mix and in preparing communities for the introduction of HIV prevention and multipurpose rings. Methods We conducted an open label single-centre randomised clinical trial of intermittent versus continuous use of NuvaRing® in Kigali, Rwanda, in 2013–2014. We randomised 120 HIV-negative women 1:1 to intermittent use (three rings with a ring-free week in between rings) or continuous use (four rings without ring-free weeks). Women underwent an interview, counselling, and a speculum examination, and were tested for pregnancy, bacterial vaginosis (BV) by Nugent scoring, yeasts and trichomonads on wet mount, and sexually transmitted infections. Findings Only one woman withdrew early. Deliberate ring removals were rare, but spontaneous ring expulsions occurred during 14% of ring use periods. There were no incident pregnancies, serious adverse events, serious social harms, or early discontinuations for safety reasons. Systemic side effects were uncommon, and local side effects were not significantly differently distributed between groups except for lower abdominal pain (P = 0.013). The incidence of vaginal yeasts during ring use was high: 22% of intermittent users and 27% of continuous users had incident vaginal yeasts at one or multiple ring removal visits (P = 0.666), and symptomatic vaginal yeast cases were more common in the continuous than intermittent users (P = 0.031). In contrast, mean Nugent scores improved over time in both groups. Conclusions Intermittent and continuous NuvaRing® use were safe in Rwandan women and improved Nugent scores over time. However, attention should be paid to ring expulsions and to a potential increased risk of vaginal candidiasis. PMID:29856848

Stroke rehabilitation at home before and after discharge reduced disability and improved quality of life: a randomised controlled trial.

PubMed

Rasmussen, Rune Skovgaard; Østergaard, Ann; Kjær, Pia; Skerris, Anja; Skou, Christina; Christoffersen, Jane; Seest, Line Skou; Poulsen, Mai Bang; Rønholt, Finn; Overgaard, Karsten

2016-03-01

To evaluate if home-based rehabilitation of inpatients improved outcome compared to standard care. Interventional, randomised, safety/efficacy open-label trial. University hospital stroke unit in collaboration with three municipalities. Seventy-one eligible stroke patients (41 women) with focal neurological deficits hospitalised in a stroke unit for more than three days and in need of rehabilitation. Thirty-eight patients were randomised to home-based rehabilitation during hospitalization and for up to four weeks after discharge to replace part of usual treatment and rehabilitation services. Thirty-three control patients received treatment and rehabilitation following usual guidelines for the treatment of stroke patients. Ninety days post-stroke the modified Rankin Scale score was the primary endpoint. Other outcome measures were the modified Barthel-100 Index, Motor Assessment Scale, CT-50 Cognitive Test, EuroQol-5D, Body Mass Index and treatment-associated economy. Thirty-one intervention and 30 control patients completed the study. Patients in the intervention group achieved better modified Rankin Scale score (Intervention median = 2, IQR = 2-3; Control median = 3, IQR = 2-4; P=0.04). EuroQol-5D quality of life median scores were improved in intervention patients (Intervention median = 0.77, IQR = 0.66-0.79; Control median = 0.66, IQR = 0.56 - 0.72; P=0.03). The total amount of home-based training in minutes highly correlated with mRS, Barthel, Motor Assessment Scale and EuroQol-5D™ scores (P-values ranging from P<0.00001 to P=0.01). Economical estimations of intervention costs were lower than total costs of standard treatment. Early home-based rehabilitation reduced disability and increased quality of life. Compared to standard care, home-based stroke rehabilitation was more cost-effective. © The Author(s) 2015.

Randomised controlled crossover trial of the effect on PtCO2 of oxygen-driven versus air-driven nebulisers in severe chronic obstructive pulmonary disease.

PubMed

Edwards, Llifon; Perrin, Kyle; Williams, Mathew; Weatherall, Mark; Beasley, Richard

2012-11-01

The comparative safety of oxygen versus air-driven nebulised bronchodilators in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain. A randomised controlled trial was performed to assess the effect on the arterial partial pressure of carbon dioxide of nebulised bronchodilator driven with oxygen versus air in stable severe COPD. In an open label randomised study, 18 subjects with stable severe COPD attended on 2 days to receive nebulised bronchodilator therapy driven by air or oxygen. Subjects received 5 mg salbutamol and 0.5 mg ipratropium bromide by nebulisation over 15 min, then, after 5 min, 5 mg salbutamol nebulised over 15 min, followed by 15 min of observation. Transcutaneous carbon dioxide tension (PtCO(2)) and oxygen saturations were recorded at 5 min intervals during the study. The primary outcome was the PtCO(2) after the completion of the second bronchodilator treatment. PtCO(2) was higher with nebulised bronchodilator therapy delivered by oxygen, but decreased back to the level associated with air nebulisation 15 min after completion of the second nebulised dose. One subject experienced an increase in PtCO(2) of 11 mm Hg after the first bronchodilator nebulisation driven by oxygen. The mean PtCO(2) difference between the oxygen and air groups after the second nebulisation was 3.1 mm Hg (95% CI 1.6 to 4.5, p<0.001). Nebulisers driven with oxygen result in significantly higher levels of PtCO(2) than those driven with air in patients with severe COPD. The study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12610000080022).

Short- versus long-duration levofloxacin plus rifampicin for acute staphylococcal prosthetic joint infection managed with implant retention: a randomised clinical trial.

PubMed

Lora-Tamayo, Jaime; Euba, Gorane; Cobo, Javier; Horcajada, Juan Pablo; Soriano, Alex; Sandoval, Enrique; Pigrau, Carles; Benito, Natividad; Falgueras, Luis; Palomino, Julián; Del Toro, María Dolores; Jover-Sáenz, Alfredo; Iribarren, José Antonio; Sánchez-Somolinos, Mar; Ramos, Antonio; Fernández-Sampedro, Marta; Riera, Melchor; Baraia-Etxaburu, Josu Mirena; Ariza, Javier

2016-09-01

Levofloxacin plus rifampicin (L+R) is the treatment of choice for acute staphylococcal prosthetic joint infection (PJI) managed with debridement and implant retention (DAIR). Long courses have been empirically recommended, but some studies have suggested that shorter treatments could be as effective. Our aim was to prove that a short treatment schedule was non-inferior to the standard long schedule. An open-label, multicentre, randomised clinical trial (RCT) was performed. Patients with an early post-surgical or haematogenous staphylococcal PJI, managed with DAIR and initiated on L+R were randomised to receive 8 weeks of treatment (short schedule) versus a long schedule (3 months or 6 months for hip or knee prostheses, respectively). The primary endpoint was cure rate. From 175 eligible patients, 63 were included (52% women; median age, 72 years): 33 patients (52%) received the long schedule and 30 (48%) received the short schedule. There were no differences between the two groups except for a higher rate of polymicrobial infection in the long-schedule group (27% vs. 7%; P = 0.031). Median follow-up was 540 days. In the intention-to-treat analysis, cure rates were 58% and 73% in patients receiving the long and short schedules, respectively (difference -15.7%, 95% CI -39.2% to 7.8%). Forty-four patients (70%) were evaluable per-protocol: cure rates were 95.0% and 91.7% for the long and short schedules, respectively (difference 3.3%, 95% CI -11.7% to 18.3%). This is the first RCT suggesting that 8 weeks of L+R could be non-inferior to longer standard treatments for acute staphylococcal PJI managed with DAIR. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Three-Component Reaction Discovery Enabled by Mass Spectrometry of Self-Assembled Monolayers

PubMed Central

Montavon, Timothy J.; Li, Jing; Cabrera-Pardo, Jaime R.; Mrksich, Milan; Kozmin, Sergey A.

2011-01-01

Multi-component reactions have been extensively employed in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform, which can be used for identification of new multi-component transformations. Our approach is based on the parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyze a previously unknown condensation of siloxy alkynes, aldehydes and amines to produce 3-hydroxy amides with high efficiency and diastereoselectivity. The reaction was further optimized using solution phase methods. PMID:22169871

Agarose droplet microfluidics for highly parallel and efficient single molecule emulsion PCR.

PubMed

Leng, Xuefei; Zhang, Wenhua; Wang, Chunming; Cui, Liang; Yang, Chaoyong James

2010-11-07

An agarose droplet method was developed for highly parallel and efficient single molecule emulsion PCR. The method capitalizes on the unique thermoresponsive sol-gel switching property of agarose for highly efficient DNA amplification and amplicon trapping. Uniform agarose solution droplets generated via a microfluidic chip serve as robust and inert nanolitre PCR reactors for single copy DNA molecule amplification. After PCR, agarose droplets are gelated to form agarose beads, trapping all amplicons in each reactor to maintain the monoclonality of each droplet. This method does not require cocapsulation of primer labeled microbeads, allows high throughput generation of uniform droplets and enables high PCR efficiency, making it a promising platform for many single copy genetic studies.

Detection of gamma-irradiation effect on DNA and protein using magnetic sensor and cyclic voltammetry.

PubMed

Park, Duck-Gun; Song, Hoon; Kishore, M B; Vértesy, G; Lee, Duk-Hyun

2013-11-01

In this study, a magnetic sensor utilizing Planar Hall Resistance (PHR) and cyclic Voltammetry (CV) for detecting the radiation effect was fabricated. Specifically, we applied in parallel a PHR sensor and CV device to monitor the irradiation effect on DNA and protein respectively. Through parallel measurements, we demonstrated that the PHR sensor and CV are sensitive enough to measure irradiation effect. The PHR voltage decreased by magnetic nanobead labeled DNA was slightly recovered after gamma ray irradiation. The behavior of cdk inhibitor protein p21 having a sandwich structure of Au/protein G/Ab/Ag/Ab was checked by monitoring the cyclic Voltammetry signal in analyzing the gamma ray irradiation effect.