Efficacy and tolerability of a fixed-dose combination of metoprolol extended release/amlodipine in patients with mild-to-moderate hypertension: a randomized, parallel-group, multicentre comparison with losartan plus amlodipine.

PubMed

Pareek, Anil; Chandurkar, Nitin B; Sharma, Ravishankar; Tiwari, Dharmendra; Gupta, Bhagwan S

2010-01-01

Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure. The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications. This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg). Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population. Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

PubMed

Madsbad, S; Kilhovd, B; Lager, I; Mustajoki, P; Dejgaard, A

2001-05-01

To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.

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.

RAPP, a systematic e-assessment of postoperative recovery in patients undergoing day surgery: study protocol for a mixed-methods study design including a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies

PubMed Central

Dahlberg, K; Odencrants, S; Hagberg, L

2016-01-01

Introduction Day surgery is a well-established practice in many European countries, but only limited information is available regarding postoperative recovery at home though there is a current lack of a standard procedure regarding postoperative follow-up. Furthermore, there is also a need for improvement of modern technology in assessing patient-related outcomes such as mobile applications. This article describes the Recovery Assessment by Phone Points (RAPP) study protocol, a mixed-methods study to evaluate if a systematic e-assessment follow-up in patients undergoing day surgery is cost-effective and improves postoperative recovery, health and quality of life. Methods and analysis This study has a mixed-methods study design that includes a multicentre, two-group, parallel, single-blind randomised controlled trial and qualitative interview studies. 1000 patients >17 years of age who are undergoing day surgery will be randomly assigned to either e-assessed postoperative recovery follow-up daily in 14 days measured via smartphone app including the Swedish web-version of Quality of Recovery (SwQoR) or to standard care (ie, no follow-up). The primary aim is cost-effectiveness. Secondary aims are (A) to explore whether a systematic e-assessment follow-up after day surgery has a positive effect on postoperative recovery, health-related quality of life (QoL) and overall health; (B) to determine whether differences in postoperative recovery have an association with patient characteristic, type of surgery and anaesthesia; (C) to determine whether differences in health literacy have a substantial and distinct effect on postoperative recovery, health and QoL; and (D) to describe day surgery patient and staff experiences with a systematic e-assessment follow-up after day surgery. The primary aim will be measured at 2 weeks postoperatively and secondary outcomes (A–C) at 1 and 2 weeks and (D) at 1 and 4 months. Trial registration number NCT02492191; Pre-results. PMID:26769788

A cognitive behavioral based group intervention for children with a chronic illness and their parents: a multicentre randomized controlled trial.

PubMed

Scholten, Linde; Willemen, Agnes M; Grootenhuis, Martha A; Maurice-Stam, Heleen; Schuengel, Carlo; Last, Bob F

2011-07-14

Coping with a chronic illness (CI) challenges children's psychosocial functioning and wellbeing. Cognitive-behavioral intervention programs that focus on teaching the active use of coping strategies may prevent children with CI from developing psychosocial problems. Involvement of parents in the intervention program may enhance the use of learned coping strategies in daily life, especially on the long-term. The primary aim of the present study is to examine the effectiveness of a cognitive behavioral based group intervention (called 'Op Koers') 1 for children with CI and of a parallel intervention for their parents. A secondary objective is to investigate why and for whom this intervention works, in order to understand the underlying mechanisms of the intervention effect. This study is a multicentre randomized controlled trial. Participants are children (8 to 18 years of age) with a chronic illness, and their parents, recruited from seven participating hospitals in the Netherlands. Participants are randomly allocated to two intervention groups (the child intervention group and the child intervention combined with a parent program) and a wait-list control group. Primary outcomes are child psychosocial functioning, wellbeing and child disease related coping skills. Secondary outcomes are child quality of life, child general coping skills, child self-perception, parental stress, quality of parent-child interaction, and parental perceived vulnerability. Outcomes are evaluated at baseline, after 6 weeks of treatment, and at a 6 and 12-month follow-up period. The analyses will be performed on the basis of an intention-to-treat population. This study evaluates the effectiveness of a group intervention improving psychosocial functioning in children with CI and their parents. If proven effective, the intervention will be implemented in clinical practice. Strengths and limitations of the study design are discussed. Current Controlled Trials ISRCTN60919570.

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

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.

Effectiveness of a mobile cooperation intervention during the clinical practicum of nursing students: a parallel group randomized controlled trial protocol.

PubMed

Strandell-Laine, Camilla; Saarikoski, Mikko; Löyttyniemi, Eliisa; Salminen, Leena; Suomi, Reima; Leino-Kilpi, Helena

2017-06-01

The aim of this study was to describe a study protocol for a study evaluating the effectiveness of a mobile cooperation intervention to improve students' competence level, self-efficacy in clinical performance and satisfaction with the clinical learning environment. Nursing student-nurse teacher cooperation during the clinical practicum has a vital role in promoting the learning of students. Despite an increasing interest in using mobile technologies to improve the clinical practicum of students, there is limited robust evidence regarding their effectiveness. A multicentre, parallel group, randomized, controlled, pragmatic, superiority trial. Second-year pre-registration nursing students who are beginning a clinical practicum will be recruited from one university of applied sciences. Eligible students will be randomly allocated to either a control group (engaging in standard cooperation) or an intervention group (engaging in mobile cooperation) for the 5-week the clinical practicum. The complex mobile cooperation intervention comprises of a mobile application-assisted, nursing student-nurse teacher cooperation and a training in the functions of the mobile application. The primary outcome is competence. The secondary outcomes include self-efficacy in clinical performance and satisfaction with the clinical learning environment. Moreover, a process evaluation will be undertaken. The ethical approval for this study was obtained in December 2014 and the study received funding in 2015. The results of this study will provide robust evidence on mobile cooperation during the clinical practicum, a research topic that has not been consistently studied to date. © 2016 John Wiley & Sons Ltd.

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

PubMed

Kołtowski, Łukasz; Aradi, Daniel; Huczek, Zenon; Tomaniak, Mariusz; Sibbing, Dirk; Filipiak, Krzysztof J; Kochman, Janusz; Balsam, Paweł; Opolski, Grzegorz

2016-01-01

High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. ClinicalTrials.gov: NCT01930773.

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.

Tretinoin Nanogel 0.025% Versus Conventional Gel 0.025% in Patients with Acne Vulgaris: A Randomized, Active Controlled, Multicentre, Parallel Group, Phase IV Clinical Trial

PubMed Central

Chandrashekhar, B S; Anitha, M.; Ruparelia, Mukesh; Vaidya, Pradyumna; Aamir, Riyaz; Shah, Sunil; Thilak, S; Aurangabadkar, Sanjeev; Pal, Sandeep; Saraswat, Abir

2015-01-01

Background: Conventional topical tretinoin formulation is often associated with local adverse events. Nanogel formulation of tretinoin has good physical stability and enables good penetration of tretinoin into the pilo-sebaceous glands. Aim: The present study was conducted to assess the efficacy and safety of a nanogel formulation of tretinoin as compared to its conventional gel formulation in the treatment of acne vulgaris of the face. Materials and Methods: This randomized, active controlled, multicentric, phase IV clinical trial evaluated the treatment of patients with acne vulgaris of the face by the two gel formulations locally applied once daily at night for 12 wk. Acne lesion counts (inflammatory, non-inflammatory & total) and severity grading were carried out on the monthly scheduled visits along with the tolerability assessments. Results: A total of 207 patients were randomized in the study. Reductions in the total (72.9% vs. 65.0%; p = 0.03) and inflammatory (78.1% vs. 66.9%; p = 0.02) acne lesions were reported to be significantly greater with the nanogel formulation as compared to the conventional gel formulation. Local adverse events were significantly less (p = 0.04) in the nanogel group (13.3%) as compared to the conventional gel group (24.7%). Dryness was the most common adverse event reported in both the treatment groups while peeling of skin, burning sensation and photosensitivity were reported in patients using the conventional gel only. Conclusion: In the treatment of acne vulgaris of the face, tretinoin nanogel formulation appears to be more effective and better tolerated than the conventional gel formulation. PMID:25738069

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.

Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.

PubMed

Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E; Mazor, Tali; Jones, Lindsey E; Wood, Matthew D; Walsh, Kyle M; Bengtsson, Henrik; Hong, Chibo; Oberndorfer, Stefan; Roetzer, Thomas; Smirnov, Ivan V; Clarke, Jennifer L; Aghi, Manish K; Chang, Susan M; Nelson, Sarah J; Woehrer, Adelheid; Phillips, Joanna J; Solomon, David A; Costello, Joseph F

2018-04-09

Rare multicentric lower-grade gliomas (LGGs) represent a unique opportunity to study the heterogeneity among distinct tumor foci in a single patient and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology, and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the 2 lesions. One patient was diagnosed with multicentric isocitrate dehydrogenase 1 (IDH1) mutated diffuse astrocytomas harboring distinct IDH1 mutations, R132H and R132C; the latter mutation has been associated with Li-Fraumeni syndrome, which was subsequently confirmed in the patient's germline DNA and shown in additional cases with The Cancer Genome Atlas data. In another patient, phylogenetic analysis of synchronously arising grade II and grade III diffuse astrocytomas demonstrated a single shared mutation, IDH1 R132H, and revealed convergent evolution via non-overlapping mutations in ATRX and TP53. In 2 cases, there was divergent evolution of IDH1-mutated and 1p/19q-codeleted oligodendroglioma and IDH1-mutated and 1p/19q-intact diffuse astrocytoma, occurring synchronously in one case and metachronously in a second. Each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors. Comprehensive sampling of these lesions can therefore significantly alter diagnosis and management. Additionally, somatic IDH1 R132C mutation in either multicentric or solitary LGG identifies unsuspected germline TP53 mutation, validating the limited number of published cases.

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

PubMed

Leung, D Y M; Hanifin, J M; Pariser, D M; Barber, K A; Langley, R G; Schlievert, P M; Abrams, B; Hultsch, T

2009-08-01

Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

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.

Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

PubMed Central

McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

2017-01-01

Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

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.

Effects of a whole body vibration (WBV) exercise intervention for institutionalized older people: a randomized, multicentre, parallel, clinical trial.

PubMed

Sitjà-Rabert, Mercè; Martínez-Zapata, Ma José; Fort Vanmeerhaeghe, Azahara; Rey Abella, Ferran; Romero-Rodríguez, Daniel; Bonfill, Xavier

2015-02-01

To assess the efficacy of an exercise program on a whole-body vibration platform (WBV) in improving body balance and muscle performance and preventing falls in institutionalized elderly people. A multicentre randomized parallel assessor-blinded clinical trial was conducted in elderly persons living in nursing homes. Participants were randomized to an exercise program performed either on a whole body vibratory platform (WBV plus exercise group) or on a stationary surface (exercise group). The exercise program for both groups consisted of static and dynamic exercises (balance and strength training over a 6-week training period of 3 sessions per week). The frequency applied on the vibratory platform was 30 to 35 Hz and amplitude was 2 to 4 mm. The primary outcome measurement was static/dynamic body balance. Secondary outcomes were muscle strength and number of falls. Efficacy was analyzed on an intention-to-treat basis and per protocol. The effects of the intervention were evaluated using the t test, Mann-Whitney test, or chi-square test, depending on the type of outcome. Follow-up measurements were collected 6 weeks and 6 months after randomization. A total of 159 participants from 10 centers were included: 81 in the WBV plus exercise group and 78 in the control group. Mean age was 82 years, and 67.29% were women. The Tinetti test score showed a significant overall improvement in both groups (P < .001). No significant differences were found between groups at week 6 (P = .890) or month 6 (P = .718). The Timed Up and Go test did not improve (P = .599) in either group over time, and no significant differences were found between groups at week 6 (P = .757) or month 6 (P = .959). Muscle performance results from the 5 Sit-To-Stand tests improved significantly across time (P = .001), but no statistically significant differences were found between groups at week 6 (P = .709) or month 6 (P = .841). A total of 57 falls (35.8%) were recorded during the follow-up period, with no differences between groups (P = .406). Exercise program on a vibratory platform provides benefits similar to those with exercise program on a stationary surface in relation to body balance, gait, functional mobility, and muscle strength in institutionalized elderly people. Longer studies in larger samples are needed to assess falls. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

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/

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.

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/

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.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

PubMed

Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-08-01

This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study

PubMed Central

Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

2013-01-01

Objectives This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. Design A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. Results In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74–1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43–0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5–3.0). Conclusion Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925. PMID:24917966

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.

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial.

PubMed

Liu, Zongjun; Shen, Li; Huang, Weijian; Zhao, Xianxian; Fang, Weiyi; Wang, Changqian; Yin, Zhaofang; Wang, Jianan; Fu, Guosheng; Liu, Xuebo; Jiang, Jianjun; Zhang, Zhihui; Li, Jingbo; Lu, Yingmin; Ge, Junbo

2017-09-01

Available data show that approximately 8%-18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy. This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population. All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China. ClinicalTrials.gov ID: NCT02900729; 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.

A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers.

PubMed

Zelen, Charles M; Gould, Lisa; Serena, Thomas E; Carter, Marissa J; Keller, Jennifer; Li, William W

2015-12-01

A prospective, randomised, controlled, parallel group, multi-centre clinical trial was conducted at three sites to compare the healing effectiveness of treatment of chronic lower extremity diabetic ulcers with either weekly applications of Apligraf(®) (Organogenesis, Inc., Canton, MA), EpiFix(®) (MiMedx Group, Inc., Marietta, GA), or standard wound care with collagen-alginate dressing. The primary study outcome was the percent change in complete wound healing after 4 and 6 weeks of treatment. Secondary outcomes included percent change in wound area per week, velocity of wound closure and a calculation of the amount and cost of Apligraf or EpiFix used. A total of 65 subjects entered the 2-week run-in period and 60 were randomised (20 per group). The proportion of patients in the EpiFix group achieving complete wound closure within 4 and 6 weeks was 85% and 95%, significantly higher (all adjusted P-values ≤ 0·003) than for patients receiving Apligraf (35% and 45%), or standard care (30% and 35%). After 1 week, wounds treated with EpiFix had reduced in area by 83·5% compared with 53·1% for wounds treated with Apligraf. Median time to healing was significantly faster (all adjusted P-values ≤0·001) with EpiFix (13 days) compared to Apligraf (49 days) or standard care (49 days). The mean number of grafts used and the graft cost per patient were lower in the EpiFix group campared to the Apligraf group, at 2·15 grafts at a cost of $1669 versus 6·2 grafts at a cost of $9216, respectively. The results of this study demonstrate the clinical and resource utilisation superiority of EpiFix compared to Apligraf or standard of care, for the treatment of diabetic ulcers of the lower extremities. © 2014 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Mindfulness-based stress reduction added to care as usual for lung cancer patients and/or their partners: A multicentre randomized controlled trial.

PubMed

Schellekens, M P J; van den Hurk, D G M; Prins, J B; Donders, A R T; Molema, J; Dekhuijzen, R; van der Drift, M A; Speckens, A E M

2017-12-01

Lung cancer patients report among the highest distress rates of all cancer patients. Partners report similar distress rates. The present study examined the effectiveness of additional mindfulness-based stress reduction (care as usual [CAU] + MBSR) versus solely CAU to reduce psychological distress in lung cancer patients and/or their partners. We performed a multicentre, parallel-group, randomized controlled trial. Mindfulness-based stress reduction is an 8-week group-based intervention, including mindfulness practice and teachings on stress. Care as usual included anticancer treatment, medical consultations, and supportive care. The primary outcome was psychological distress. Secondary outcomes included quality of life, caregiver burden, relationship satisfaction, mindfulness skills, self-compassion, rumination, and posttraumatic stress symptoms. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up. Linear mixed modeling was conducted on an intention-to-treat sample. Moderation (gender, disease stage, baseline distress, participation with/without partner) and mediation analyses were performed. A total of 31 patients and 21 partners were randomized to CAU + MBSR and 32 patients and 23 partners to CAU. After CAU + MBSR patients reported significantly less psychological distress (p = .008, d = .69) than after CAU. Baseline distress moderated outcome: those with more distress benefitted most from MBSR. Additionally, after CAU + MBSR patients showed more improvements in quality of life, mindfulness skills, self-compassion, and rumination than after CAU. In partners, no differences were found between groups. Our findings suggest that psychological distress in lung cancer patients can be effectively treated with MBSR. No effect was found in partners, possibly because they were more focused on patients' well-being rather than their own. Copyright © 2017 John Wiley & Sons, Ltd.

Online versus Live Delivery of Education to Pharmacists in a Large Multicentre Health Region: A Non-inferiority Assessment of Learning Outcomes.

PubMed

Taylor, Robert; Jung, Joanne; Loewen, Peter; Spencer, Carrie; Dossa, Anar; de Lemos, Jane

2013-07-01

The prevalence of online modules for continuing education in the health professions has been increasing in recent years. However, the effectiveness of online modules for pharmacist learning has not been thoroughly studied. The primary aim of this study was to determine if providing education to pharmacists through a self-paced enhanced online module was non-inferior to a face-to-face learning module with respect to knowledge application on the topic of postoperative insulin dosing. Secondary aims were to determine pharmacists' knowledge gain and retention, as well as their satisfaction with the modules. The participants in this prospective, randomized, parallel-group non-inferiority trial were pharmacists in a large multicentre health region. Outcomes were measured by comparing scores obtained on pre- and post-module knowledge-assessment questionnaires. A between-group difference in change on knowledge application scores of less than 25 percentage points was the predetermined non-inferiority margin. A total of 74 pharmacists consented to participate, 38 randomly assigned to use the enhanced online module and 36 to attend the face-to-face learning session. For questions examining knowledge application, the mean improvement achieved by the online learning group was 26 percentage points greater than that achieved by the face-to-face learning group (95% confidence interval [CI] 25 to 27; p < 0.001). For questions testing knowledge gain, the improvement achieved by the online learning group was 7 percentage points less than that achieved by the face-to-face learning group (95% CI 2 to 12; p = 0.008). Therefore, the enhanced online module was deemed to be non-inferior to the face-to-face learning session in terms of knowledge application and knowledge gain. Insufficient data were available to analyze the secondary outcome of knowledge retention over time. Participant satisfaction was similar for the 2 groups (p = 0.62). The self-paced enhanced online module was non-inferior to facilitated face-to-face learning in terms of improving application and knowledge of insulin dosing. Pharmacists had similar levels of satisfaction with the 2 modes of learning.

CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients

PubMed Central

Molloy, Alexander J; Clarke, France; Herridge, Margaret S; Koo, Karen K Y; Rudkowski, Jill; Seely, Andrew J E; Pellizzari, Joseph R; Tarride, Jean-Eric; Mourtzakis, Marina; Karachi, Timothy; Cook, Deborah J

2016-01-01

Introduction Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. Methods and analysis 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. Ethics and dissemination Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. Trial registration number NCT02377830; Pre-results. PMID:27059469

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.

Diclofenac patch for topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study

PubMed Central

Predel, H; Koll, R; Pabst, H; Dieter, R; Gallacchi, G; Giannetti, B; Bulitta, M; Heidecker, J; Mueller, E

2004-01-01

Objectives: To investigate the clinical efficacy and safety of a newly developed diclofenac patch in the topical treatment of blunt impact injuries. Methods: This was a randomised, placebo controlled, double blind, multicentre study in 120 patients with traumatic blunt soft tissue injury. Within 3 h of the injury participants of sport competitions and training camps were enrolled and treated twice daily with the diclofenac or a placebo patch over a period of 7 days. Patients were randomised (1:1) to two parallel groups. Tenderness produced by pressure was measured twice daily during the first 3 days after enrolment as well as at day 7. Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient. Results: The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group. Conclusions: A newly developed diclofenac patch is effective and safe for the treatment of blunt impact injuries. PMID:15155436

Moxibustion for treating knee osteoarthritis: study protocol of a multicentre randomised controlled trial

PubMed Central

2013-01-01

Background The treatment of knee osteoarthritis, which is a major cause of disability among the elderly, is typically selected from multidisciplinary options, including complementary and alternative medicine. Moxibustion has been used in the treatment of knee osteoarthritis in Korea to reduce pain and improve physical activity. However, there is no sufficient evidence of its effectiveness, and it cannot therefore be widely recommended for treating knee osteoarthritis. We designed a randomised controlled clinical trial to evaluate the effectiveness, safety, cost-effectiveness, and qualitative characteristics of moxibustion treatment of knee osteoarthritis compared to usual care. Methods/designs This is a protocol for a multicentre, pragmatic, randomised, assessor-blinded, controlled, parallel-group study. A total of 212 participants will be assigned to the moxibustion group (n = 106) and the usual care group (n = 106) at 4 clinical research centres. The participants assigned to the moxibustion group will receive moxibustion treatment of the affected knee(s) at 6 standard acupuncture points (ST36, ST35, ST34, SP9, Ex-LE04, and SP10) 3 times per week for 4 weeks (a total of 12 sessions). Participants in the usual care group will not receive moxibustion treatment during the study period. Follow-up will be performed on the 5th and 13th weeks after random allocation. Both groups will be allowed to use any type of treatment, including surgery, conventional medication, physical treatment, acupuncture, herbal medicine, over-the-counter drugs, and other active treatments. Educational material that explains knee osteoarthritis, the current management options, and self-exercise will be provided to each group. The global scale of the Korean Western Ontario and McMaster Osteoarthritis Index (K-WOMAC) will be the primary outcome measurement used in this study. Other subscales (pain, stiffness, and function) of the K-WOMAC, the Short-Form 36v2 Health Survey, the Beck Depression Inventory, the Physical Function test, Patient Global Assessment, and the Pain Numerical Rating Scale will be used as outcome variables to evaluate the effectiveness of moxibustion. Safety will be assessed at every visit. In addition, an economic evaluation and a qualitative study will be conducted as a mixed-methods approach. Discussion This trial may contribute to developing evidence for the effectiveness and safety of moxibustion for treating knee osteoarthritis. Trial registration Trial registration number: KCT0000130 PMID:23497032

Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial.

PubMed

Diener, Markus K; Seiler, Christoph M; Rossion, Inga; Kleeff, Jörg; Glanemann, Matthias; Butturini, Giovanni; Tomazic, Ales; Bruns, Christiane J; Busch, Olivier R C; Farkas, Stefan; Belyaev, Orlin; Neoptolemos, John P; Halloran, Christopher; Keck, Tobias; Niedergethmann, Marco; Gellert, Klaus; Witzigmann, Helmut; Kollmar, Otto; Langer, Peter; Steger, Ulrich; Neudecker, Jens; Berrevoet, Frederik; Ganzera, Silke; Heiss, Markus M; Luntz, Steffen P; Bruckner, Thomas; Kieser, Meinhard; Büchler, Markus W

2011-04-30

The ideal closure technique of the pancreas after distal pancreatectomy is unknown. We postulated that standardised closure with a stapler device would prevent pancreatic fistula more effectively than would a hand-sewn closure of the remnant. This multicentre, randomised, controlled, parallel group-sequential superiority trial was done in 21 European hospitals. Patients with diseases of the pancreatic body and tail undergoing distal pancreatectomy were eligible and were randomly assigned by central randomisation before operation to either stapler or hand-sewn closure of the pancreatic remnant. Surgical performance was assessed with intraoperative photo documentation. The primary endpoint was the combination of pancreatic fistula and death until postoperative day 7. Patients and outcome assessors were masked to group assignment. Interim and final analysis were by intention to treat in all patients in whom a left resection was done. This trial is registered, ISRCTN18452029. Between Nov 16, 2006, and July 3, 2009, 450 patients were randomly assigned to treatment groups (221 stapler; 229 hand-sewn closure), of whom 352 patients (177 stapler, 175 hand-sewn closure) were analysed. Pancreatic fistula rate or mortality did not differ between stapler (56 [32%] of 177) and hand-sewn closure (49 [28%] of 175; OR 0·84, 95% CI 0·53–1·33; p=0·56). One patient died within the fi rst 7 days after surgery in the hand-sewn group; no deaths occurred in the stapler group. Serious adverse events did not differ between groups. Stapler closure did not reduce the rate of pancreatic fistula compared with hand-sewn closure for distal pancreatectomy. New strategies, including innovative surgical techniques, need to be identified to reduce this adverse outcome. German Federal Ministry of Education and Research.

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.

A multicentre, randomized, single-blind, parallel-group study comparing the efficacy and tolerability of benzoyl peroxide 3%/clindamycin 1% with azelaic acid 20% in the topical treatment of mild-to-moderate acne vulgaris.

PubMed

Schaller, M; Sebastian, M; Ress, C; Seidel, D; Hennig, M

2016-06-01

Mild-to-moderate acne vulgaris is treated with a range of mono- and combination therapies; however, clinical evidence is still required to optimize treatment recommendations. To compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild-to-moderate acne vulgaris. This was a randomized, assessor-blinded, parallel-group, multicentre study conducted in Germany. Patients with a confirmed diagnosis of acne vulgaris, aged 12-45 years, were randomized 1 : 1 to once-daily BPO + CLN gel or twice-daily AzA cream for up to 12 weeks. The primary endpoint was the percentage change in inflammatory lesions from baseline at Week 4. Secondary endpoints included total and inflammatory lesion counts and tolerability assessments. For selected secondary endpoints, inductive statistical analysis was performed post hoc. Patient safety was assessed by adverse event (AE) monitoring. Efficacy was assessed in the modified intent-to-treat (mITT) population [patients using ≥1 dose of study medication (ITT), plus baseline and ≥1 post-baseline lesion count (n = 215)]. There was a statistically significant difference in the primary endpoint, with a median decrease of -52.6% for BPO + CLN (n = 107) vs.-38.8% for AzA (n = 108; P = 0.0004). There was also a greater difference in secondary lesion endpoints at Week 12, with a median decrease in inflammatory lesions of -78.8% and -65.3% and total lesions of -69.0% and -53.9% with BPO + CLN and AzA, respectively (both P < 0.0001). Tolerability was acceptable for both treatments. Overall, 55.6% (BPO + CLN) and 69.7% (AzA) of patients reported treatment-emergent AEs, and 15.7% and 35.8% of patients experienced application site reactions with BPO + CLN (24 events; 17 patients) and AzA (60 events; 39 patients) treatment, respectively (ITT population). BPO + CLN demonstrated greater efficacy than AzA in the treatment of mild-to-moderate acne vulgaris and has a positive tolerability and safety profile. © 2016 European Academy of Dermatology and Venereology.

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

Johnson, Julie K; Barach, Paul; Vernooij-Dassen, Myrra

2012-12-01

A multicentre, multinational research study requires careful planning and coordination to accomplish the aims of the study and to ensure systematic and rigorous examination of all project methods and data collected. The aim of this paper is to describe the approach we used during the HANDOVER Project to develop a multicentre, multinational research project for studying transitions of patient care while creating a community of practice for the researchers. We highlight the process used to assure the quality of a multicentre qualitative study and to create a codebook for data analysis as examples of attending to the community of practice while conducting rigorous qualitative research. Essential elements for the success of this multinational, multilanguage research project included recruiting a strong research team, explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalise upon those differences. Although not commonly discussed in reports of large research projects, there is an underlying, concurrent stream of activities to develop a cohesive team that trusts and respects one another's skills and that engage independent researchers in a group process that contributes to achieving study goals. We discuss other lessons learned and offer recommendations for other teams planning multicentre research.

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

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.

Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.

PubMed

Tipold, A; Keefe, T J; Löscher, W; Rundfeldt, C; de Vries, F

2015-04-01

The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Three years of GH treatment in Turner's syndrome: complex effect of GH dosage on growth parameters. French Pediatric Clinics and Sanofi-Winthrop.

PubMed

Bertrand, A M; Chaussain, J L; Job, B; Mariani, R; Ponte, C; Rappaport, R; Rochiccioll, P; Chatelain, P

1996-06-01

There have been few studies of GH dose responses in Turner's syndrome. We have therefore compared the growth effect of two doses of subcutaneous GH: 0.45 (D1) or 0.90 (D2) IU/kg/week. Multicentre study with two parallel randomized groups treated with D1 or D2 dose for one year, then with D2 for the second and third years in both groups. Ninety-seven girls with Turner's syndrome aged from 4.8 to 16.5 years. The first mean height velocity (HV) was significantly higher with D2. At one year the girls changed from D1 to D2 showed a further acceleration in HV. During second and third years HV remained above the mean for untreated Turner girls, in both groups. Mean cumulative height gains over the 3 years were 1.06 and 1.17 SDS/CA (Ranke's Turner standard) in groups G1 and G2 respectively. Bone maturation, over 36 months, was 33.7 (G1) and 31.9 (G2) months. These results suggest that, if a higher initial GH dose is associated with a greater net initial height gain, the duration of treatment might affect the long-term results. Intermittent treatment should be considered.

[Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen].

PubMed

Zhou, Yun-feng; Wei, Yu-long; Zhang, Pu-lin; Gao, Shan; Ning, Guo-li; Zhang, Zhen-qiang; Hu, Bin; Wang, Dan-yi; Yan, Mei-rong; Liu, Wen-jun

2006-06-01

To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen. One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed. Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001). The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients.

PubMed

Kho, Michelle E; Molloy, Alexander J; Clarke, France; Herridge, Margaret S; Koo, Karen K Y; Rudkowski, Jill; Seely, Andrew J E; Pellizzari, Joseph R; Tarride, Jean-Eric; Mourtzakis, Marina; Karachi, Timothy; Cook, Deborah J

2016-04-08

Early exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT. 60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0-4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1-2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics. Each participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors. NCT02377830; 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/

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.

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).

Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study.

PubMed

Kelly, Sue; Davies, Emyr; Fearns, Simon; McKinnon, Carol; Carter, Rick; Gerlinger, Christoph; Smithers, Andrew

2010-01-01

The combined oral contraceptive Yasmin (drospirenone 3 mg plus ethinylestradiol 30 microg [DRSP 3 mg/EE 30 microg]) has been shown to be a well tolerated and effective combination that provides high contraceptive reliability and good cycle control. Furthermore, DRSP 3 mg/EE 30 microg has been shown to have a positive effect on premenstrual symptoms and well-being/health-related quality of life, and to improve the skin condition of women with acne. To date, however, there have been relatively few studies that have compared the effects of DRSP 3 mg/EE 30 microg on the general well-being of women with those of other oral contraceptives. To compare the impact of DRSP 3 mg/EE 30 microg with that of levonorgestrel 150 microg/EE 30 microg (LNG 150 microg/EE 30 microg; Microgynon 30) on various parameters associated with well-being in healthy female subjects. This was a randomized, single-blind, parallel-group, multicentre study conducted using 21/7-day regimens of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg over seven cycles. Efficacy parameters included: changes in Menstrual Distress Questionnaire (MDQ) normative T scores; the proportion of subjects with acne; and menstrual symptoms. Cycle control and subjective well-being parameters were also assessed. Treatment with DRSP 3 mg/EE 30 microg had similar beneficial effects on symptoms of water retention and impaired concentration to LNG 150 microg/EE 30 microg, but was significantly better in alleviating negative affect symptoms during the menstrual phase (median difference in MDQ T score -3; p = 0.027; Wilcoxon rank sum test). The proportion of subjects with acne decreased from approximately 55% to approximately 45% in the DRSP 3 mg/EE 30 microg group, but remained static at approximately 60% in the LNG 150 microg/EE 30 microg group. Somatic and psychological symptoms occurred at the greatest intensity and for most subjects during the menstrual phase of the cycle in both groups. Both drugs had similar cycle control parameters with a tendency towards reduced bleeding with continued use. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being (60% vs 46%; p = 0.035; chi-squared [chi2] test). Emotional well-being was reported improved in 61% and 51% of DRSP 3 mg/EE 30 microg and LNG 150 microg/EE 30 microg users, respectively (p = 0.1190; chi2 test). Adverse events were typical of oral contraceptive use and did not give rise to any safety concerns. Both products had similar beneficial effects on symptoms of water retention and impaired concentration, but DRSP 3 mg/EE 30 microg was significantly better in alleviating negative affect symptoms during the menstrual phase. The proportion of subjects with acne decreased in the DRSP 3 mg/EE 30 microg group but not in the LNG 150 microg/EE 30 microg group. More subjects in the DRSP 3 mg/EE 30 microg group reported improved physical well-being compared with the LNG 150 microg/EE 30 microg group.

Phenotypic Description of the Spanish Multicentre Genetic Glaucoma Group Cohort

PubMed Central

Gamundi, Maria José; Duch, Susana; Rios, Jose; Carballo, Miguel; Study Group, EMEIGG

2017-01-01

Introduction The aim of the study was to make a phenotypic description of the Spanish multicentre glaucoma group cohort of patients. Design Retrospective, observational, multicentre, cohort study. Material and Methods The clinical charts of 152 patients with hereditary glaucoma from18 Spanish eye centres were reviewed in order to make an epidemiologic description of the type of glaucoma and associated factors. True hereditary cases were compared with familiar cases according to the Gong et al. criteria. Results 61% were true hereditary cases and 39% familiar cases. Ocular comorbidity, optic disc damage, and visual field mean defect were significantly more severe in hereditary patients, who required significantly more first-line hypotensive drugs and surgical interventions to control intraocular pressure than familiar patients. Conclusions The strength of the hereditary component of glaucoma seems to worsen the clinical course, causing more structural and functional damage and requiring more intense glaucoma treatment. The family history of glaucoma should be carefully investigated and taken into consideration when making treatment decisions or intensifying previous treatment. PMID:29082038

Securing All intraVenous devices Effectively in hospitalised patients--the SAVE trial: study protocol for a multicentre randomised controlled trial.

PubMed

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-09-23

Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. 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.

[Sentinel node biopsy in patients with multifocal and multicentric breast cancer: A 5-year follow-up].

PubMed

Blanco Saiz, I; López Carballo, M T; Martínez Fernández, J; Carrión Maldonado, J; Cabrera Pereira, A; Moral Alvarez, S; Santamaría Girón, L; Cantero Cerquella, F; López Secades, A; Díaz González, D; Llaneza Folgueras, A; Aira Delgado, F J

2014-01-01

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months). Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis

PubMed Central

Evans, E Glyn V; Sigurgeirsson, Bárdur

1999-01-01

Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatmentContinuous terbinafine should be the current treatment of choice for onychomycosis PMID:10205099

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.

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

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.

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © 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 randomized study of new sling exercise treatment vs traditional physiotherapy for patients with chronic whiplash-associated disorders with unsettled compensation claims.

PubMed

Vikne, John; Oedegaard, Arit; Laerum, Even; Ihlebaek, Camilla; Kirkesola, Gitle

2007-04-01

Many patients with chronic whiplash-associated disorders have reduced neuromuscular control of the neck and head. It has been proposed that a new sling exercise therapy may promote neuromuscular control of the neck. To compare the effects of traditional physiotherapy vs traditional physiotherapy combined with a new sling exercise therapy on discomfort and function in patients with chronic whiplash-associated disorders who have unsettled compensation claims; and to investigate possible additional effects of guided, long-term home training. A randomized multi-centre trial with 4 parallel groups. A total of 214 patients were assigned randomly to 4 treatment groups, and received either traditional physiotherapy with or without home training, or new sling exercise therapy with or without home training. Outcome measures were pain, disability, psychological distress, sick leave and physical tests. A total of 171 patients (80%) completed the study. There were no important statistical or clinical differences between the groups after 4 months of treatment. There was a small statistically significant effect at 12-month follow-up in both groups with home training regarding pain during rest (p = 0.05) and reported fatigue in the final week (p = 0.02). No statistically significant differences were found between the traditional physiotherapy group and the new sling exercise group, with or without home training. Since the groups were not compared with a control group without treatment, we cannot conclude that the studied treatments are effective for patients with whiplash-associated disorder, only that they did not differ in our study.

Determining Surgical Complications in the Overweight (DISCOVER): a multicentre observational cohort study to evaluate the role of obesity as a risk factor for postoperative complications in general surgery.

PubMed

Nepogodiev, Dmitri; Chapman, Stephen J; Glasbey, James; Kelly, Michael; Khatri, Chetan; Drake, Thomas M; Kong, Chia Yew; Mitchell, Harriet; Harrison, Ewen M; Fitzgerald, J Edward; Bhangu, Aneel

2015-07-20

Obesity is increasingly prevalent among patients undergoing surgery. Conflicting evidence exists regarding the impact of obesity on postoperative complications. This multicentre study aims to determine whether obesity is associated with increased postoperative complications following general surgery. This prospective, multicentre cohort study will be performed utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency, gastrointestinal, bariatric or hepatobiliary surgery will be included. Day case patients will be excluded. The primary end point will be the overall 30-day major complication rate (Clavien-Dindo grade III-V complications). Data will be collected to risk-adjust outcomes for potential confounding factors, such as preoperative cardiac risk. This study will be disseminated through structured medical student networks using established collaborative methodology. The study will be powered to detect a two-percentage point increase in the major postoperative complication rate in obese versus non-obese patients. Following appropriate assessment, an exemption from full ethics committee review has been received, and the study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through national and local research collaborative networks. 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.

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

Oxidative stress in dogs with multicentric lymphoma: Effect of chemotherapy on oxidative and antioxidant biomarkers.

PubMed

Bottari, Nathieli B; Munhoz, Thiago D; Torbitz, Vanessa D; Tonin, Alexandre A; Anai, Letícia A; Semolin, Lívia M S; Jark, Paulo C; Bollick, Yãnaí S; Moresco, Rafael N; França, Raqueli T; Lopes, Sonia T A; Stefani, Lenita M; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

2015-01-01

Lymphoma is one of the most common types of cancer in dogs, characterized by the proliferation of lymphoid cells. The treatment of this type of cancer is usually based on drugs with high toxicity, which can cause severe side effects. Therefore, the aim of this study was to measure the levels of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), and ferric reducing antioxidant power (FRAP) in dogs with multicentric lymphoma before and after chemotherapy. For this purpose, serum samples of 25 dogs diagnosed with multicentric lymphoma and 15 healthy dogs were used. The animals were exposed to CHOP chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisone) and serum samples were collected 5 weeks after treatment. High levels of TBARS, AOPP, and FRAP were observed in sera of dogs with multicentric lymphoma when compared to healthy dogs (P < 0.01), and even higher levels (TBARS and AOPP) were found after chemotherapy i.e. treatment exacerbated the oxidative stress levels. On the other hand, FRAP levels did not differ statistically between animals with lymphoma before and after treatment (P > 0.05). Exacerbated oxidative stress was observed in dogs with multicentric lymphoma Group II (Stage IV-V: involvement of lymph nodes and organs) compared to those in Group I (Stage I-III: only affected lymph nodes) of the disease, as well as the dogs with clinical signs and T immunophenotype. Another important result was observed after chemotherapy, where FRAP levels were higher in dogs that showed complete disease remission compared to animals with progressive disease. Therefore, dogs with lymphoma showed protein oxidation and lipid peroxidation, as well as increased total antioxidants before and after chemotherapy compared to the control group.

Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol).

PubMed

Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Poulsen, Henrik Enghusen; Nielsen, René Ernst; Berk, Michael; Dean, Olivia May; Mohebbi, Mohammadreza; Nielsen, Connie Thuroee

2018-04-05

Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress. In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences. Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.

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

COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol.

PubMed

Goldstein, Laura H; Mellers, John D C; Landau, Sabine; Stone, Jon; Carson, Alan; Medford, Nick; Reuber, Markus; Richardson, Mark; McCrone, Paul; Murray, Joanna; Chalder, Trudie

2015-06-27

The evidence base for the effectiveness of psychological interventions for patients with dissociative non-epileptic seizures (DS) is currently extremely limited, although data from two small pilot randomised controlled trials (RCTs), including from our group, suggest that Cognitive Behavioural Therapy (CBT) may be effective in reducing DS occurrence and may improve aspects of psychological status and psychosocial functioning. The study is a multicentre, pragmatic parallel group RCT to evaluate the clinical and cost-effectiveness of specifically-tailored CBT plus standardised medical care (SMC) vs SMC alone in reducing DS frequency and improving psychological and health-related outcomes. In the initial screening phase, patients with DS will receive their diagnosis from a neurologist/epilepsy specialist. If patients are eligible and interested following the provision of study information and a booklet about DS, they will consent to provide demographic information and fortnightly data about their seizures, and agree to see a psychiatrist three months later. We aim to recruit ~500 patients to this screening stage. After a review three months later by a psychiatrist, those patients who have continued to have DS in the previous eight weeks and who meet further eligibility criteria will be told about the trial comparing CBT + SMC vs SMC alone. If they are interested in participating, they will be given a further booklet on DS and study information. A research worker will see them to obtain their informed consent to take part in the RCT. We aim to randomise 298 people (149 to each arm). In addition to a baseline assessment, data will be collected at 6 and 12 months post randomisation. Our primary outcome is monthly seizure frequency in the preceding month. Secondary outcomes include seizure severity, measures of seizure freedom and reduction, psychological distress and psychosocial functioning, quality of life, health service use, cost effectiveness and adverse events. We will include a nested qualitative study to evaluate participants' views of the intervention and factors that acted as facilitators and barriers to participation. This study will be the first adequately powered evaluation of CBT for this patient group and offers the potential to provide an evidence base for treating this patient group. Current Controlled Trials ISRCTN05681227 ClinicalTrials.gov NCT02325544.

A multi-centre randomised controlled trial of rehabilitation aimed at improving outdoor mobility for people after stroke: Study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person’s quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. Methods/design This is a multi-centre parallel group individually randomised, controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to four months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood information is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. Discussion This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012. Trial registration ISRCTN58683841 PMID:22721452

Montelukast (Singulair) and Pregnancy

MedlinePlus

... 2009. Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes Eur J Clin Pharmacol. ... Conditions of Use Site By: Marketing and Advertising Design Group

Effects of person-centred care on health outcomes-A randomized controlled trial in patients with acute coronary syndrome.

PubMed

Pirhonen, Laura; Olofsson, Elisabeth Hansson; Fors, Andreas; Ekman, Inger; Bolin, Kristian

2017-02-01

To study the effects of person-centred care provided to patients with acute coronary syndrome, using four different health-related outcome measures. Also, to examine the performance of these outcomes when measuring person-centred care. The data used in this study consists of primary data from a multicentre randomized parallel group, controlled intervention study for patients with acute coronary syndrome at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention and control group consisted of 94 and 105 patients, respectively. The effect of the intervention on health-related outcomes was estimated, controlling for socio-economic and disease-related variables. Patients in the intervention group reported significantly higher general self-efficacy than those in the control group six months after intervention start-up. Moreover, the intervention group returned to work in a greater extent than controls; their physical activity level had increased more and they had a higher EQ-5D score, meaning higher health-related quality of life. These latter effects are not significant but are all pointing towards the beneficial effects of person-centred care. All the effects were estimated while controlling for important socio-economic and disease-related variables. The effectiveness of person-centred care varies between different outcomes considered. A statistically significant beneficial effect was found for one of the four outcome measures (self-efficacy). The other measures all captured beneficial, but not significant, effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

PubMed Central

van Rijthoven, A W; Dijkmans, B A; Goei The, H S; Hermans, J; Montnor-Beckers, Z L; Jacobs, P C; Cats, A

1986-01-01

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs. PMID:3532966

Randomized multicentre trial comparing external and internal pancreatic stenting during pancreaticoduodenectomy.

PubMed

Jang, J-Y; Chang, Y R; Kim, S-W; Choi, S H; Park, S J; Lee, S E; Lim, C-S; Kang, M J; Lee, H; Heo, J S

2016-05-01

There is no consensus on the best method of preventing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). This multicentre, parallel group, randomized equivalence trial investigated the effect of two ways of pancreatic stenting after PD on the rate of POPF. Patients undergoing elective PD or pylorus-preserving PD with duct-to-mucosa pancreaticojejunostomy were enrolled from four tertiary referral hospitals. Randomization was stratified according to surgeon with a 1 : 1 allocation ratio to avoid any related technical factors. The primary endpoint was clinically relevant POPF rate. Secondary endpoints were nutritional index, remnant pancreatic volume, long-term complications and quality of life 2 years after PD. A total of 328 patients were randomized to the external (164 patients) or internal (164) stent group between August 2010 and January 2014. The rates of clinically relevant POPF were 24·4 per cent in the external and 18·9 per cent in the internal stent group (risk difference 5·5 per cent). As the 90 per cent confidence interval (-2·0 to 13·0 per cent) did not fall within the predefined equivalence limits (-10 to 10 per cent), the clinically relevant POPF rates in the two groups were not equivalent. Similar results were observed for patients with soft pancreatic texture and high fistula risk score. Other postoperative outcomes were comparable between the two groups. Five stent-related complications occurred in the external stent group. Multivariable analysis revealed that soft pancreatic texture, non-pancreatic disease and high body mass index (23·3 kg/m 2 or above) predicted clinically relevant POPF. External stenting after PD was associated with a higher rate of clinically relevant POPF than internal stenting. Registration number: NCT01023594 (https://www.clinicaltrials.gov). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

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.

Effects of combined exercise training and electromyostimulation treatments in chronic heart failure: A prospective multicentre study.

PubMed

Iliou, Marie C; Vergès-Patois, Bénédicte; Pavy, Bruno; Charles-Nelson, Anais; Monpère, Catherine; Richard, Rudy; Verdier, Jean C

2017-08-01

Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure. It is a valuable method for the improvement of exercise tolerance. Some studies reported a similar improvement with quadricipital electrical myostimulation, but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospective multicentre study. Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and/or muscular strength in cardiac heart failure patients. Methods Ninety-one patients were included (mean age: 58 ± 9 years; New York Heart Association II/III: 52/48%, left ventricular ejection fraction: 30 ± 7%) in a prospective French study. The patients were randomised into two groups: 41 patients in exercise training and 50 in exercise training + electrical myostimulation. All patients underwent 20 exercise training sessions. In addition, in the exercise training + electrical myostimulation group, patients underwent 20 low frequency (10 Hz) quadricipital electrical myostimulation sessions. Each patient underwent a cardiopulmonary exercise test, a six-minute walk test, a muscular function evaluation and a quality of life questionnaire, before and at the end of the study. Results A significant improvement of exercise capacity (Δ peak oxygen uptake+15% in exercise training group and +14% in exercise training + electrical myostimulation group) and of quality of life was observed in both groups without statistically significant differences between the two groups. Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group. Conclusions This prospective multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients.

Clobetasol propionate shampoo 0.05%: a new option to treat patients with moderate to severe scalp psoriasis.

PubMed

Jarratt, Michael; Breneman, Debra; Gottlieb, Alice B; Poulin, Yves; Liu, Yin; Foley, Valerie

2004-01-01

Psoriasis is a chronic, papulosquamous condition that affects up to 2% of the U.S. population. Approximately 50% of patients with psoriasis have involvement of the scalp. This was a multicentre, randomized, vehicle-controlled, double-masked and parallel-group study. The aim was to evaluate the efficacy and safety of clobetasol propionate shampoo, 0.05% versus its corresponding vehicle in subjects aged 12 years and older with moderate to severe scalp psoriasis over a treatment period of 4 weeks. Recurrence of scalp psoriasis was assessed during a two week follow-up period. A total of 142 subjects were treated. Results after 4 weeks demonstrated that clobetasol propionate shampoo, 0.05% was with a similar safety profile significantly more effective than its vehicle. The novel short contact shampoo formulation of clobetasol propionate is convenient and efficacious and minimizes systemic exposure while being efficient, safe and well-tolerated in the treatment of moderate to severe scalp psoriasis.

[Multicentric prospective randomized study evaluating the interest of intravaginal electro-stimulation at home for urinary incontinence after prior perineal reeducation. Interim analysis].

PubMed

Lopès, P; Levy-Toledano, R; Chiarelli, P; Rimbault, F; Marès, P

2014-03-01

Perineal reeducation of stress urinary incontinence is beneficial in 80% of cases. However, patients have to perform self-retraining exercises of the perineal muscles at home, in order to maintain the benefit of the physiotherapy. The aim of this study is to assess the benefit of GYNEFFIK(®), a perineal electro-stimulator, during this home-care phase. Women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI) that responded to physiotherapy were included in this study in two parallel groups. The groups followed a self-reeducation program, with or without GYNEFFIK(®) electro-stimulation sessions. The comparison of the two groups was based on the rate of women for whom the benefit of the initial perineal reeducation was maintained (defined as non-worsening ICIQ and Ditrovie scales' score). According to the protocol, an interim analysis was performed on 95 patients (i.e. almost half of the expected sample size) who had had at least one evaluation under treatment, among which 44 patients had finished the study. The therapeutic benefit of the initial perineal reeducation was maintained in 87.8% of the GYNEFFIK(®) patient group, while it was maintained in 52.2% (P=0.0001) in the usual care group (i.e. who did not use electro-stimulation). Likewise, patient had a more favorable subjective impression when using GYNEFFIK(®) (83.7% versus 60.0% in the usual care group) as they felt that they improved during the study. In the GYNEFFIK(®) group, no increase in symptoms was reported, whereas almost one out of five patients in the usual care group felt that their condition had worsened. Copyright © 2014. Published by Elsevier SAS.

Individualised pelvic floor muscle training in women with pelvic organ prolapse (POPPY): a multicentre randomised controlled trial.

PubMed

Hagen, Suzanne; Stark, Diane; Glazener, Cathryn; Dickson, Sylvia; Barry, Sarah; Elders, Andrew; Frawley, Helena; Galea, Mary P; Logan, Janet; McDonald, Alison; McPherson, Gladys; Moore, Kate H; Norrie, John; Walker, Andrew; Wilson, Don

2014-03-01

Pelvic organ prolapse is common and is strongly associated with childbirth and increasing age. Women with prolapse are often advised to do pelvic floor muscle exercises, but evidence supporting the benefits of such exercises is scarce. We aimed to establish the effectiveness of one-to-one individualised pelvic floor muscle training for reducing prolapse symptoms. We did a parallel-group, multicentre, randomised controlled trial at 23 centres in the UK, one in New Zealand, and one in Australia, between June 22, 2007, and April 9, 2010. Female outpatients with newly-diagnosed, symptomatic stage I, II, or III prolapse were randomly assigned (1:1), by remote computer allocation with minimsation, to receive an individualised programme of pelvic floor muscle training or a prolapse lifestyle advice leaflet and no muscle training (control group). Outcome assessors, and investigators who were gynaecologists at trial sites, were masked to group allocation; the statistician was masked until after data analysis. Our primary endpoint was participants' self-report of prolapse symptoms at 12 months. Analysis was by intention-to-treat analysis. This trial is registered, number ISRCTN35911035. 447 eligible patients were randomised to the intervention group (n=225) or the control group (n=222). 377 (84%) participants completed follow-up for questionnaires at 6 months and 295 (66%) for questionnaires at 12 months. Women in the intervention group reported fewer prolapse symptoms (ie, a significantly greater reduction in the pelvic organ prolapse symptom score [POP-SS]) at 12 months than those in the control group (mean reduction in POP-SS from baseline 3.77 [SD 5.62] vs 2.09 [5.39]; adjusted difference 1.52, 95% CI 0.46-2.59; p=0.0053). Findings were robust to missing data. Eight adverse events (six vaginal symptoms, one case of back pain, and one case of abdominal pain) and one unexpected serious adverse event, all in women from the intervention group, were regarded as unrelated to the intervention or to participation in the study. One-to-one pelvic floor muscle training for prolapse is effective for improvement of prolapse symptoms. Long-term benefits should be investigated, as should the effects in specific subgroups. Chief Scientist Office of the Scottish Government Health and Social Care Directorates, New Zealand Lottery Board, and National Health and Medical Research Council (Australia). Copyright © 2014 Elsevier Ltd. All rights reserved.

Effectiveness and cost-effectiveness of telephone-based support versus usual care for treatment of pressure ulcers in people with spinal cord injury in low-income and middle-income countries: study protocol for a 12-week randomised controlled trial.

PubMed

Arora, Mohit; Harvey, Lisa Anne; Hayes, Alison Joy; Chhabra, Harvinder Singh; Glinsky, Joanne Valentina; Cameron, Ian Douglas; Lavrencic, Lucija; Arumugam, Narkeesh; Hossain, Sohrab; Bedi, Parneet Kaur

2015-07-28

Pressure ulcers are a common and severe complication of spinal cord injury, particularly in low-income and middle-income countries where people often need to manage pressure ulcers alone and at home. Telephone-based support may help people in these situations to manage their pressure ulcers. The aim of this study is to determine the effectiveness and cost-effectiveness of telephone-based support to help people with spinal cord injury manage pressure ulcers at home in India and Bangladesh. A multicentre (3 sites), prospective, assessor-blinded, parallel, randomised controlled trial will be undertaken. 120 participants with pressure ulcers on the sacrum, ischial tuberosity or greater trochanter of the femur secondary to spinal cord injury will be randomly assigned to a Control or Intervention group. Participants in the Control group will receive usual community care. That is, they will manage their pressure ulcers on their own at home but will be free to access whatever healthcare support they can. Participants in the Intervention group will also manage their pressure ulcers at home and will also be free to access whatever healthcare support they can, but in addition they will receive weekly telephone-based support and advice for 12 weeks (15-25 min/week). The primary outcome is the size of the pressure ulcer at 12 weeks. 13 secondary outcomes will be measured reflecting other aspects of pressure ulcer resolution, depression, quality of life, participation and satisfaction with healthcare provision. An economic evaluation will be run in parallel and will include a cost-effectiveness and a cost-utility analysis. Ethical approval was obtained from the Institutional Ethics Committee at each site. The results of this study will be disseminated through publications and presented at national and international conferences. ACTRN12613001225707. 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.

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

PubMed

Misawa, Sonoko; Kuwabara, Satoshi; Sato, Yasunori; Yamaguchi, Nobuko; Nagashima, Kengo; Katayama, Kanako; Sekiguchi, Yukari; Iwai, Yuta; Amino, Hiroshi; Suichi, Tomoki; Yokota, Takanori; Nishida, Yoichiro; Kanouchi, Tadashi; Kohara, Nobuo; Kawamoto, Michi; Ishii, Junko; Kuwahara, Motoi; Suzuki, Hidekazu; Hirata, Koichi; Kokubun, Norito; Masuda, Ray; Kaneko, Juntaro; Yabe, Ichiro; Sasaki, Hidenao; Kaida, Ken-Ichi; Takazaki, Hiroshi; Suzuki, Norihiro; Suzuki, Shigeaki; Nodera, Hiroyuki; Matsui, Naoko; Tsuji, Shoji; Koike, Haruki; Yamasaki, Ryo; Kusunoki, Susumu

2018-06-01

Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals. Copyright © 2018 Elsevier Ltd. All rights reserved.

One-stop-shop with confocal microscopy imaging vs. standard care for surgical treatment of basal cell carcinoma: an open-label, noninferiority, randomized controlled multicentre trial.

PubMed

Kadouch, D J; Elshot, Y S; Zupan-Kajcovski, B; van Haersma de With, A S E; van der Wal, A C; Leeflang, M; Jóźwiak, K; Wolkerstorfer, A; Bekkenk, M W; Spuls, P I; de Rie, M A

2017-09-01

Routine punch biopsies are considered to be standard care for diagnosing and subtyping basal cell carcinoma (BCC) when clinically suspected. We assessed the efficacy of a one-stop-shop concept using in vivo reflectance confocal microscopy (RCM) imaging as a diagnostic tool vs. standard care for surgical treatment in patients with clinically suspected BCC. In this open-label, parallel-group, noninferiority, randomized controlled multicentre trial we enrolled patients with clinically suspected BCC at two tertiary referral centres in Amsterdam, the Netherlands. Patients were randomly assigned to the RCM one-stop-shop (diagnosing and subtyping using RCM followed by direct surgical excision) or standard care (planned excision based on the histological diagnosis and subtype of a punch biopsy). The primary outcome was the proportion of patients with tumour-free margins after surgical excision of BCC. Of the 95 patients included, 73 (77%) had a BCC histologically confirmed using a surgical excision specimen. All patients (40 of 40, 100%) in the one-stop-shop group had tumour-free margins. In the standard-care group tumour-free margins were found in all but two patients (31 of 33, 94%). The difference in the proportion of patients with tumour-free margins after BCC excision between the one-stop-shop group and the standard-care group was -0·06 (90% confidence interval -0·17-0·01), establishing noninferiority. The proposed new treatment strategy seems suitable in facilitating early diagnosis and direct treatment for patients with BCC, depending on factors such as availability of RCM, size and site of the lesion, patient preference and whether direct surgical excision is feasible. © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Accelerated Titration of Oxytocin in Nulliparous Women with Labour Dystocia: Results of the ACTION Pilot Randomized Controlled Trial.

PubMed

Dy, Jessica; Rainey, Jenna; Walker, Mark C; Fraser, William; Smith, Graeme N; White, Ruth Rennicks; Waddell, Patti; Janoudi, Ghayath; Corsi, Daniel J; Wei, Shu Qin

2018-06-01

The primary objective was to determine the feasibility of a large RCT assessing the effectiveness of an accelerated oxytocin titration (AOT) protocol compared with a standard gradual oxytocin titration (GOT) in reducing the risk of CS in nulliparous women diagnosed with dystocia in the first stage of labour. The secondary objective was to obtain preliminary data on the safety and efficacy of the foregoing AOT protocol. This was a multicentre, double-masked, parallel-group pilot RCT. This study was conducted in three Canadian birthing centres. A total of 79 term nulliparous women carrying a singleton pregnancy in spontaneous labour, with a diagnosis of labour dystocia, were randomized to receive either GOT (initial dose 2 mU/min with increments of 2 mU/min) or AOT (initial dose 4 mU/min with increments of 4 mU/min), in a 1:1 ratio. An intention-to-treat analysis was applied. A total of 252 women were screened and approached, 137 (54.4%) consented, and 79 (31.3%) were randomized. Overall protocol adherence was 76 of 79 (96.2%). Of the women randomized, 10 (25.6%) allocated to GOT had a CS compared with six (15.0%) allocated to AOT (Fisher exact test P = 0.27). This pilot study demonstrated that a large, multicentre RCT is not only feasible, but also necessary to assess the effectiveness and safety of an AOT protocol for labour augmentation with regard to CS rate and indicators of maternal and perinatal morbidities. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. 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.

Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial

PubMed Central

Rickard, Claire M; Marsh, Nicole; Webster, Joan; Playford, E Geoffrey; McGrail, Matthew R; Larsen, Emily; Keogh, Samantha; McMillan, David; Whitty, Jennifer A; Choudhury, Md Abu; Dunster, Kimble R; Reynolds, Heather; Marshall, Andrea; Crilly, Julia; Young, Jeanine; Thom, Ogilvie; Gowardman, John; Corley, Amanda; Fraser, John F

2015-01-01

Introduction Over 70% of all hospital admissions have a peripheral intravenous device (PIV) inserted; however, the failure rate of PIVs is unacceptably high, with up to 69% of these devices failing before treatment is complete. Failure can be due to dislodgement, phlebitis, occlusion/infiltration and/or infection. This results in interrupted medical therapy; painful phlebitis and reinsertions; increased hospital length of stay, morbidity and mortality from infections; and wasted medical/nursing time. Appropriate PIV dressing and securement may prevent many cases of PIV failure, but little comparative data exist regarding the efficacy of various PIV dressing and securement methods. This trial will investigate the clinical and cost-effectiveness of 4 methods of PIV dressing and securement in preventing PIV failure. Methods and analysis A multicentre, parallel group, superiority randomised controlled trial with 4 arms, 3 experimental groups (tissue adhesive, bordered polyurethane dressing, sutureless securement device) and 1 control (standard polyurethane dressing) is planned. There will be a 3-year recruitment of 1708 adult patients, with allocation concealment until randomisation by a centralised web-based service. The primary outcome is PIV failure which includes any of: dislodgement, occlusion/infiltration, phlebitis and infection. Secondary outcomes include: types of PIV failure, PIV dwell time, costs, device colonisation, skin colonisation, patient and staff satisfaction. Relative incidence rates of device failure per 100 devices and per 1000 device days with 95% CIs will summarise the impact of each dressing, and test differences between groups. Kaplan-Meier survival curves (with log-rank Mantel-Cox test) will compare device failure over time. p Values of <0.05 will be considered significant. Secondary end points will be compared between groups using parametric or non-parametric techniques appropriate to level of measurement. Ethics and dissemination Ethical approval has been received from Queensland Health (HREC/11/QRCH/152) and Griffith University (NRS/46/11/HREC). Results will be published according to the CONSORT statement and presented at relevant conferences. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN); 12611000769987. PMID:26399574

Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol.

PubMed

Wiesinger, Herbert; Berse, Matthias; Klein, Stefan; Gschwend, Simone; Höchel, Joachim; Zollmann, Frank S; Schütt, Barbara

2015-12-01

The present study was conducted to investigate the influence of the strong CYP3A4 inhibitor ketoconazole (KTZ) on the pharmacokinetics of drospirenone (DRSP) administered in combination with ethinylestradiol (EE) or estradiol (E2). This was a randomized, multicentre, open label, one way crossover, fixed sequence study with two parallel treatment arms. A group sequential design allowed terminating the study for futility after first study cohort. About 50 healthy young women were randomized 1 : 1 to 'DRSP/EE' or 'DRSP/E2'. Subjects in the 'DRSP/EE' group received DRSP 3 mg/EE 0.02 mg (YAZ®, Bayer) once daily for 21 to 28 days followed by DRSP 3 mg/EE 0.02 mg once daily plus KTZ 200 mg twice daily for 10 days. Subjects in the 'DRSP/E2' group received DRSP 3 mg/E2 1.5 mg (research combination) once daily for 21 to 28 days followed by DRSP 3 mg/E2 1.5 mg once daily plus KTZ 200 mg twice daily for 10 days. Oral co-administration of DRSP/EE or DRSP/E2 and KTZ resulted in an increase in DRSP exposure (AUC(0,24 h)) in both treatment groups: DRSP/EE group: 2.68-fold DRSP increase (90% CI 2.44, 2.95); DRSP/E2 group: 2.30-fold DRSP increase (90% CI 2.08, 2.54). EE and estrone (metabolite of E2) exposures were increased ~1.4-fold whereas E2 exposure was largely unaffected by KTZ co-administration. A moderate pharmacokinetic drug-drug interaction between DRSP and KTZ was demonstrated in this study. No relevant changes of medical concern were detected in the safety data collected in this study. © 2015 The British Pharmacological Society.

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

PubMed

Peréz Busquier, M; Calero, E; Rodríguez, M; Castellon Arce, P; Bermudez, A; Linares, L F; Mesa, J; Ffernandez Crisostomos, C; Garcia, C; Garcia Lopez, A; Valenzuela, A; Povedano, A; Garcia Perez, S; Lopez, M A; Caliz, R; Garcia Villalba, F; Cano, M; Gines Martinez, F; Gonzalez, J; Caracuel, M A; Roldan, R; Guzman Ubeda, M; Gonzalez, A; Marenco de la Fuente, I L; Alepuz Pou, M

1997-03-01

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

Emergence agitation during recovery from intracranial surgery under general anaesthesia: a protocol and statistical analysis plan for a prospective multicentre cohort study.

PubMed

Yan, Li-Mei; Chen, Han; Yu, Rong-Guo; Wang, Zhu-Heng; Zhou, Guan-Hua; Wang, Yong-Jin; Zhang, Xia; Xu, Ming; Chen, Lu; Zhou, Jian-Xin

2015-04-21

Emergence agitation after intracranial surgery is an important clinical issue during anaesthesia recovery. The aim of this multicentre cohort study is to investigate the incidence of emergence agitation, identify the risk factors and determine clinical outcomes in adult patients after intracranial surgery under general anaesthesia. Additionally, we will deliberately clarify the relationship between postoperative pneumocephalus and agitation. The present study is a prospective multicentre cohort study. Five intensive care units (ICUs) in China will participate in the study. Consecutive adult patients admitted to the ICUs after intracranial surgery will be enrolled. Sedation-Agitation Scale (SAS) or Richmond Agitation-Sedation Scale (RASS) will be used to evaluate the patients 12 h after the enrolment. Agitation is defined as an SAS score of 5-7, or an RASS score of +2 to +4. According to the maximal SAS and RASS score, patients will be divided into two cohorts: the agitation group and the non-agitation group. Factors potentially related to emergence agitation will be collected at study entry, during anaesthesia and operation, during postoperative care. Univariate analyses between the agitation and the non-agitation groups will be performed. The stepwise backward logistic regression will be carried out to identify the independent predictors of agitation. Patients will be followed up for 72 h after the operation. Accidental self-extubation of the endotracheal tube and removal of other catheters will be documented. The use of sedatives and analgesics will be collected. Ethics approval has been obtained from each of five participating hospitals. Study findings will be disseminated through peer-reviewed publications and conference presentations. NCT02318199. 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 large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.

PubMed

Müller, Hans-Peter; Turner, Martin R; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

2016-06-01

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. 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/

Fusidic acid suspension twice daily: a new treatment schedule for skin and soft tissue infection in children, with improved tolerability.

PubMed

Török, Eva; Somogyi, Tihamér; Rutkai, Krisztina; Iglesias, Luis; Bielsa, Isabel

2004-06-01

This multicentre, randomized, double-blind, parallel group study aimed to compare a new regimen of fusidic acid suspension against a standard regimen in children with skin and soft tissue infections. Treatment groups were given either a new regimen of fusidic acid suspension (20 mg/kg divided b.i.d.) or a standard regimen (50 mg/kg divided t.i.d.), which were administered for 5 days in both groups and for a further 5 days if evidence of infection persisted. Assessment of those cured was carried out 14 days. Both regimens were effective. Cure was achieved in 194 (91.1%) of the 213 children given the new b.i.d. dosage and for 194 (89.4%) of the 217 children given the standard t.i.d. dosage (intention-to-treat population; p=0.72). Cure was maintained at the follow-up assessment for 94.8% (181 of 191) and 95.7% (180 of 188), respectively, of the children. Bacteriological cure of infections due to fusidic acid susceptible Staphylococcus aureus and/or group A beta-haemolytic streptococci, with elimination of pathogens, was achieved in all 121 (100%) children treated with the new b.i.d. regimen and in 123 (99.2%) of the 124 children treated with the standard TID regimen. The new twice-daily regimen had significantly better tolerance (p=0.025).

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.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

PubMed

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, 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/.

Large multi-centre pilot randomized controlled trial testing a low-cost, tailored, self-help smoking cessation text message intervention for pregnant smokers (MiQuit).

PubMed

Naughton, Felix; Cooper, Sue; Foster, Katharine; Emery, Joanne; Leonardi-Bee, Jo; Sutton, Stephen; Jones, Matthew; Ussher, Michael; Whitemore, Rachel; Leighton, Matthew; Montgomery, Alan; Parrott, Steve; Coleman, Tim

2017-07-01

To estimate the effectiveness of pregnancy smoking cessation support delivered by short message service (SMS) text message and key parameters needed to plan a definitive trial. Multi-centre, parallel-group, single-blinded, individual randomized controlled trial. Sixteen antenatal clinics in England. Four hundred and seven participants were randomized to the intervention (n = 203) or usual care (n = 204). Eligible women were < 25 weeks gestation, smoked at least one daily cigarette (> 5 pre-pregnancy), were able to receive and understand English SMS texts and were not already using text-based cessation support. All participants received a smoking cessation leaflet; intervention participants also received a 12-week programme of individually tailored, automated, interactive, self-help smoking cessation text messages (MiQuit). Seven smoking outcomes, including validated continuous abstinence from 4 weeks post-randomization until 36 weeks gestation, design parameters for a future trial and cost-per-quitter. Using the validated, continuous abstinence outcome, 5.4% (11 of 203) of MiQuit participants were abstinent versus 2.0% (four of 204) of usual care participants [odds ratio (OR) = 2.7, 95% confidence interval (CI) = 0.93-9.35]. The Bayes factor for this outcome was 2.23. Completeness of follow-up at 36 weeks gestation was similar in both groups; provision of self-report smoking data was 64% (MiQuit) and 65% (usual care) and abstinence validation rates were 56% (MiQuit) and 61% (usual care). The incremental cost-per-quitter was £133.53 (95% CI = -£395.78 to 843.62). There was some evidence, although not conclusive, that a text-messaging programme may increase cessation rates in pregnant smokers when provided alongside routine NHS cessation care. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial.

PubMed

Knowles, Charles H; Horrocks, Emma J; Bremner, Stephen A; Stevens, Natasha; Norton, Christine; O'Connell, P Ronan; Eldridge, Sandra

2015-10-24

Percutaneous tibial nerve stimulation (PTNS) is a new ambulatory therapy for faecal incontinence. Data from case series suggest it has beneficial outcomes in 50-80% patients; however its effectiveness against sham electrical stimulation has not been investigated. We therefore aimed to assess the short-term efficacy of PTNS against sham electrical stimulation in adults with faecal incontinence. We did a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial (CONtrol of Faecal Incontinence using Distal NeuromodulaTion [CONFIDeNT]) in 17 specialist hospital units in the UK that had the skills to manage patients with faecal incontinence. Eligible participants aged 18 years or older with substantial faecal incontinence for whom conservative treatments (such as dietary changes and pelvic floor exercises) had not worked, were randomly assigned (1:1) to receive either PTNS (via the Urgent PC neuromodulation system) or sham stimulation (via a transcutaneous electrical nerve stimulation machine to the lateral forefoot) once per week for 12 weeks. Randomisation was done with permuted block sizes of two, four, and six, and was stratified by sex and then by centre for women. Patients and outcome assessors were both masked to treatment allocation for the 14-week duration of the trial (but investigators giving the treatment were not masked). The primary outcome was a clinical response to treatment, which we defined as a 50% or greater reduction in episodes of faecal incontinence per week. We assessed this outcome after 12 treatment sessions, using data from patients' bowel diaries. Analysis was by intention to treat, and missing data were multiply imputed. This trial is registered with the ISRCTN registry, number 88559475, and is closed to new participants. Between Jan 23, 2012, and Oct 31, 2013, we randomly assigned 227 eligible patients (of 373 screened) to receive either PTNS (n=115) or sham stimulation (n=112). 12 patients withdrew from the trial: seven from the PTNS group and five from the sham group (mainly because they could not commit to receiving treatment every week). Two patients (one in each group) withdrew because of an adverse event that was unrelated to treatment (exacerbation of fibromyalgia and rectal bleeding). 39 (38%) of 103 patients with full data from bowel diaries in the PTNS group had a 50% or greater reduction in the number of episodes of faecal incontinence per week compared with 32 (31%) of 102 patients in the sham group (adjusted odds ratio 1·28, 95% CI 0·72-2·28; p=0·396). No serious adverse events related to treatment were reported in the trial. Seven mild, related adverse events were reported in each treatment group, mainly pain at the needle site (four in PTNS, three in sham). PTNS given for 12 weeks did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. Further studies are warranted to determine its efficacy in the long term, and in patient subgroups (ie, those with urgency). National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

Beyond silence: protocol for a randomized parallel-group trial comparing two approaches to workplace mental health education for healthcare employees.

PubMed

Moll, Sandra; Patten, Scott Burton; Stuart, Heather; Kirsh, Bonnie; MacDermid, Joy Christine

2015-04-16

Mental illness is a significant and growing problem in Canadian healthcare organizations, leading to tremendous personal, social and financial costs for individuals, their colleagues, their employers and their patients. Early and appropriate intervention is needed, but unfortunately, few workers get the help that they need in a timely way due to barriers related to poor mental health literacy, stigma, and inadequate access to mental health services. Workplace education and training is one promising approach to early identification and support for workers who are struggling. Little is known, however, about what approach is most effective, particularly in the context of healthcare work. The purpose of this study is to compare the impact of a customized, contact-based education approach with standard mental health literacy training on the mental health knowledge, stigmatized beliefs and help-seeking/help-outreach behaviors of healthcare employees. A multi-centre, randomized, two-group parallel group trial design will be adopted. Two hundred healthcare employees will be randomly assigned to one of two educational interventions: Beyond Silence, a peer-led program customized to the healthcare workplace, and Mental Health First Aid, a standardized literacy based training program. Pre, post and 3-month follow-up surveys will track changes in knowledge (mental health literacy), attitudes towards mental illness, and help-seeking/help-outreach behavior. An intent-to-treat, repeated measures analysis will be conducted to compare changes in the two groups over time in terms of the primary outcome of behavior change. Linear regression modeling will be used to explore the extent to which knowledge, and attitudes predict behavior change. Qualitative interviews with participants and leaders will also be conducted to examine process and implementation of the programs. This is one of the first experimental studies to compare outcomes of standard mental health literacy training to an intervention with an added anti-stigma component (using best-practices of contact-based education). Study findings will inform recommendations for designing workplace mental health education to promote early intervention for employees with mental health issues in the context of healthcare work. May 2014 - ClinicalTrials.gov: NCT02158871.

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

PubMed Central

Vojtaššák, Jozef; Vojtaššák, Jozef; Jacobs, Adam; Rynn, Leonie; Waechter, Sandra; Richarz, Ute

2011-01-01

Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment. PMID:22110921

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 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.

General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial.

PubMed

Lewis, S C; Warlow, C P; Bodenham, A R; Colam, B; Rothwell, P M; Torgerson, D; Dellagrammaticas, D; Horrocks, M; Liapis, C; Banning, A P; Gough, M; Gough, M J

2008-12-20

The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. The Health Foundation (UK) and European Society of Vascular Surgery.

Nocturnal emergency department visits, duration of symptoms and risk of hospitalisation among adults with asthma exacerbations: a multicentre observational study.

PubMed

Yasuda, Hideto; Hagiwara, Yusuke; Watase, Hiroko; Hasegawa, Kohei

2016-08-12

We sought to compare the characteristics of patients with asthma presenting to the emergency department (ED) during the night-time with those of patients presenting at other times of the day, and to determine whether the time of ED presentation is associated with the risk of hospitalisation. A multicentre chart review study of 23 EDs across Japan. Patients aged 18-54 years with a history of physician-diagnosed asthma, presented to the ED between January 2009 and December 2011 OUTCOME MEASURES: The outcome of interest was hospitalisation, including admissions to an observation unit, inpatient unit and intensive care unit. Among the 1354 patients (30.1% in the night-time group vs 69.9% in the other time group) included in this study, the median age was 34 years and ∼40% were male. Overall 145 patients (10.7%) were hospitalised. Patients in the night-time group were more likely to have a shorter duration of symptoms (≤3 hours) before ED presentation than those in the other time group (25.9% in night-time vs 13.4% in other times; p<0.001). In contrast, there were no significant differences in respiratory rate, initial peak expiratory flow or ED asthma treatment between the two groups (p>0.05). Similarly, the risk of hospitalisation did not differ between the two groups (11.3% in night-time vs 10.5% in other times; p=0.65). In a multivariable model adjusting for potential confounders, the risk of hospitalisation in the night-time group was not statistically different from the other time group (OR, 1.10; 95% CI 0.74 to 1.61; p=0.63). This multicentre study in Japan demonstrated no significant difference in the risk of hospitalisations according to the time of ED presentation. 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/

Correction to: Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study.

PubMed

Marx, Gernot

2018-01-01

The members of the SepNet Critical Care Trials Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

A randomized, investigator-masked clinical evaluation of the efficacy and safety of clobetasol propionate 0.05% shampoo and tar blend 1% shampoo in the treatment of moderate to severe scalp psoriasis.

PubMed

Griffiths, Christopher E M; Finlay, Andrew Y; Fleming, Colin J; Barker, Jonathan N W N; Mizzi, Fabienne; Arsonnaud, Stéphanie

2006-01-01

The clinical benefit of currently available tar blend shampoos for the treatment of scalp psoriasis is restricted due to their limited efficacy, low cosmetic appeal and potential for carcinogenicity. This 4-week multicentre, randomized, parallel-group, investigator-masked study included 162 subjects and aimed to compare the efficacy, safety and cosmetic acceptability of clobetasol propionate 0.05% shampoo versus a currently marketed tar blend 1% shampoo in subjects with moderate to severe scalp psoriasis. Clobetasol propionate shampoo was superior to tar blend shampoo with respect to all efficacy variables tested (p<0.001): Total and Global Severity Score; erythema; plaque thickening; desquamation; pruritus; total scalp area involved; and the subject's global assessment of clinical improvement. Both treatments were safe and well-tolerated. Furthermore, more subjects indicated that clobetasol propionate shampoo was more cosmetically acceptable than tar blend shampoo. Clobetasol propionate 0.05% shampoo is a good alternative to tar blend shampoo in the treatment of moderate to severe scalp psoriasis.

Ex post facto assessment of diffusion tensor imaging metrics from different MRI protocols: preparing for multicentre studies in ALS.

PubMed

Rosskopf, Johannes; Müller, Hans-Peter; Dreyhaupt, Jens; Gorges, Martin; Ludolph, Albert C; Kassubek, Jan

2015-03-01

Diffusion tensor imaging (DTI) for assessing ALS-associated white matter alterations has still not reached the level of a neuroimaging biomarker. Since large-scale multicentre DTI studies in ALS may be hampered by differences in scanning protocols, an approach for pooling of DTI data acquired with different protocols was investigated. Three hundred and nine datasets from 170 ALS patients and 139 controls were collected ex post facto from a monocentric database reflecting different scanning protocols. A 3D correction algorithm was introduced for a combined analysis of DTI metrics despite different acquisition protocols, with the focus on the CST as the tract correlate of ALS neuropathological stage 1. A homogenous set of data was obtained by application of 3D correction matrices. Results showed that a fractional anisotropy (FA) threshold of 0.41 could be defined to discriminate ALS patients from controls (sensitivity/specificity, 74%/72%). For the remaining test sample, sensitivity/specificity values of 68%/74% were obtained. In conclusion, the objective was to merge data recorded with different DTI protocols with 3D correction matrices for analyses at group level. These post processing tools might facilitate analysis of large study samples in a multicentre setting for DTI analysis at group level to aid in establishing DTI as a non-invasive biomarker for ALS.

Double-blind multicentre UK hospital studies of isoxicam vs naproxen

PubMed Central

Cardoe, N.; Hart, F. Dudley

1986-01-01

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks. 10 Patients thought that isoxicam was more effective than naproxen, to a significant difference. 11 In both trials, the two drugs were well tolerated and had similar side effects profiles, with the majority of adverse experiences being associated with the digestive system; no side effect was severe. PMID:3620277

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

Does one size really fit all? The effectiveness of a non-diagnosis-specific integrated mental health care program in Germany in a prospective, parallel-group controlled multi-centre trial.

PubMed

Mueller-Stierlin, Annabel Sandra; Helmbrecht, Marina Julia; Herder, Katrin; Prinz, Stefanie; Rosenfeld, Nadine; Walendzik, Julia; Holzmann, Marco; Dinc, Uemmueguelsuem; Schützwohl, Matthias; Becker, Thomas; Kilian, Reinhold

2017-08-01

The Network for Mental Health (NWpG-IC) is an integrated mental health care program implemented in 2009 by cooperation between health insurance companies and community mental health providers in Germany. Meanwhile about 10,000 patients have been enrolled. This is the first study evaluating the effectiveness of the program in comparison to standard mental health care in Germany. In a parallel-group controlled trial over 18 months conducted in five regions across Germany, a total of 260 patients enrolled in NWpG-IC and 251 patients in standard mental health care (TAU) were recruited between August 2013 and November 2014. The NWpG-IC patients had access to special services such as community-based multi-professional teams, case management, crisis intervention and family-oriented psychoeducation in addition to standard mental health care. The primary outcome empowerment (EPAS) and the secondary outcomes quality of life (WHO-QoL-BREF), satisfaction with psychiatric treatment (CSQ-8), psychosocial and clinical impairment (HoNOS) and information about mental health service needs (CAN) were measured four times at 6-month intervals. Linear mixed-effect regression models were used to estimate the main effects and interaction effects of treatment, time and primary diagnosis. Due to the non-randomised group assignment, propensity score adjustment was used to control the selection bias. NWpG-IC and TAU groups did not differ with respect to most primary and secondary outcomes in our participating patients who showed a broad spectrum of psychiatric diagnoses and illness severities. However, a significant improvement in terms of patients' satisfaction with psychiatric care and their perception of treatment participation in favour of the NWpG-IC group was found. Providing integrated mental health care for unspecific mentally ill target groups increases treatment participation and service satisfaction but seems not suitable to enhance the overall outcomes of mental health care in Germany. The implementation of strategies for ameliorating the needs orientation of the NWpG-IC should be considered. German Clinical Trial Register DRKS00005111 , registered 26 July 2013.

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

CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.

PubMed

Carling, Anna; Forsberg, Anette; Gunnarsson, Martin; Nilsagård, Ylva

2017-09-01

Imbalance leading to falls is common in people with multiple sclerosis (PwMS). To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5). A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up. Post-intervention, the exercise group showed statistically significant improvement ( p = 0.015) in BBS and borderline significant improvement in MS Walking Scale ( p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before ( p < 0.001; p < 0.004). This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.

Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.

PubMed

Jörres, A; Gahl, G M; Dobis, C; Polenakovic, M H; Cakalaroski, K; Rutkowski, B; Kisielnicka, E; Krieter, D H; Rumpf, K W; Guenther, C; Gaus, W; Hoegel, J

1999-10-16

There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane. 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate). At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension). There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment.

PubMed

Bytzer, Peter; Morocutti, Anna; Kennerly, Peter; Ravic, Miroslav; Miller, Neil

2006-10-01

Gastro-oesophageal reflux disease (GORD) symptoms have a significant impact on patients' well-being. Onset of symptom relief is therefore an important consideration in GORD treatment. The primary objective was to compare the efficacy of rabeprazole (20 mg) and omeprazole (20 mg) regarding onset of heartburn control during the first 7 days of treatment in patients with erosive oesophagitis. Secondary objectives included maintenance of sustained heartburn control, control of other GORD symptoms (e.g. acid regurgitation, epigastric pain, dysphagia), effect on quality of life, patient satisfaction with treatment, and adverse events. In this multicentre, randomized, parallel-group, double-blind, comparative study, performed in Europe and Iceland, patients with endoscopically confirmed erosive oesophagitis were randomized to receive once-daily treatment with rabeprazole 20 mg (n=358) or omeprazole 20 mg (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale) twice daily by the patients on their diary cards. Median time to reach heartburn control was 1.5 days for both the rabeprazole and omeprazole groups (p<0.43). The results were similar between treatments for other study parameters. Both treatments were well tolerated. Unlike previous studies, no significant differences were found between treatments with rabeprazole (20 mg) and omeprazole (20 mg) in this study. Further studies are needed to evaluate the potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole, with respect to onset of symptom control in erosive GORD.

Multicenter external validation of two malignancy risk prediction models in patients undergoing 18F-FDG-PET for solitary pulmonary nodule evaluation.

PubMed

Perandini, Simone; Soardi, G A; Larici, A R; Del Ciello, A; Rizzardi, G; Solazzo, A; Mancino, L; Zeraj, F; Bernhart, M; Signorini, M; Motton, M; Montemezzi, S

2017-05-01

To achieve multicentre external validation of the Herder and Bayesian Inference Malignancy Calculator (BIMC) models. Two hundred and fifty-nine solitary pulmonary nodules (SPNs) collected from four major hospitals which underwent 18-FDG-PET characterization were included in this multicentre retrospective study. The Herder model was tested on all available lesions (group A). A subgroup of 180 SPNs (group B) was used to provide unbiased comparison between the Herder and BIMC models. Receiver operating characteristic (ROC) area under the curve (AUC) analysis was performed to assess diagnostic accuracy. Decision analysis was performed by adopting the risk threshold stated in British Thoracic Society (BTS) guidelines. Unbiased comparison performed In Group B showed a ROC AUC for the Herder model of 0.807 (95 % CI 0.742-0.862) and for the BIMC model of 0.822 (95 % CI 0.758-0.875). Both the Herder and the BIMC models were proven to accurately predict the risk of malignancy when tested on a large multicentre external case series. The BIMC model seems advantageous on the basis of a more favourable decision analysis. • The Herder model showed a ROC AUC of 0.807 on 180 SPNs. • The BIMC model showed a ROC AUC of 0.822 on 180 SPNs. • Decision analysis is more favourable to the BIMC model.

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis.

PubMed

Thomas, Peter W; Thomas, Sarah; Kersten, Paula; Jones, Rosemary; Nock, Alison; Slingsby, Vicky; Green, Colin; Baker, Roger; Galvin, Kate; Hillier, Charles

2010-06-16

Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Current Controlled Trials ISRCTN76517470.

Do patients diagnosed with Alzheimer's disease benefit from a psycho-educational programme for family caregivers? A randomised controlled study.

PubMed

de Rotrou, Jocelyne; Cantegreil, Inge; Faucounau, Véronique; Wenisch, Emilie; Chausson, Catherine; Jegou, David; Grabar, Sophie; Rigaud, Anne-Sophie

2011-08-01

The Aide dans la Maladie d'Alzheimer (AIDMA) study was conducted to determine whether a psycho-educational programme (PEP) for primary caregivers in addition to standard anti-dementia drugs for patients improves caregivers' psychological condition and patients' activities of daily life. Multicentre randomised controlled intervention trial. One hundred and sixty-seven dyads 'patient-caregiver' were recruited from 15 French memory clinics and randomised in two parallel groups. The intervention group was offered the PEP in 12 group sessions for 3 months. The control group had usual care. Patients in both groups with mild to moderate Alzheimer's disease (AD) were diagnosed and treated with pharmacotherapy. Patients' primary efficacy variable was functional status assessed with the Disability Assessment Scale for Dementia (DAD) scale. Alzheimer Disease Assessment Scale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) were secondary criteria. Caregivers' first outcome measure was depressive symptoms assessed with the Montgomery and Asberg Depression Rating Scale (MADRS) scale. Zarit scale, Sense of Competence Questionnaire (SCQ) and Visual Analogue Scales (VAS) were secondary criteria. Assessment was done at baseline, 3 months (M3, end of intervention) and 6 months (M6). Patients' stabilisation was observed in both groups. In caregivers, significant improvement in disease understanding at M3 (p = 0.007) and M6 (p = 0.0001) and in ability to cope with care-recipients' disease at M6 (0.02) was evidenced. The PEP had no additional impact on patients but carers developed more effective disease understanding and ability of coping. Results support the idea that the PEP although improving caregivers' condition is not sufficient to improve patients' activities in daily life which requires additional individually tailored interventions provided by professionals. Copyright © 2010 John Wiley & Sons, Ltd.

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.

Taliglucerase alfa: safety and efficacy across 6 clinical studies in adults and children with Gaucher disease.

PubMed

Zimran, Ari; Wajnrajch, Michael; Hernandez, Betina; Pastores, Gregory M

2018-02-23

Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment of adult and paediatric patients with Type 1 Gaucher disease (GD) in several countries and the first plant cell-expressed recombinant therapeutic protein approved by the US Food and Drug Administration for humans. Here, we review the findings across six key taliglucerase alfa clinical studies. A total of 33 treatment-naïve adult patients were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 9-month, multicentre, randomized, double-blind, parallel-group, dose-comparison pivotal study, after which eligible patients continued into two consecutive extension studies; 17 treatment-naïve adult patients completed 5 total years of treatment with taliglucerase alfa. In the only ERT study focused on exclusively paediatric patients with GD, 11 treatment-naïve children were randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 12-month, multicentre, double-blind study; nine completed 3 total years of treatment in a dedicated paediatric extension study. The effect of switching patients from imiglucerase to taliglucerase alfa was also investigated in a separate 9-month study that included 26 adults and five children; 10 adults completed a total of 3 years and two children completed a total of 2.75 years of taliglucerase alfa treatment in the extension studies. All studies evaluated safety and spleen volume, liver volume, platelet count, haemoglobin concentration, and biomarkers as measures of efficacy. Detailed results from baseline through the end of these studies are presented. Taliglucerase alfa was well tolerated, and adverse events were generally mild/moderate in severity and transient. Treatment with taliglucerase alfa resulted in improvements (treatment-naïve patients) or stability (patients switched from imiglucerase) in visceral, haematologic, and biomarker parameters. Together, this comprehensive data set supports the treatment of adult and paediatric patients with GD who are naïve to ERT or who have previously been treated with imiglucerase.

Low-dose intravenous immunoglobulin treatment for complex regional pain syndrome (LIPS): study protocol for a randomized controlled trial.

PubMed

Goebel, Andreas; Shenker, Nicholas; Padfield, Nick; Shoukrey, Karim; McCabe, Candida; Serpell, Mick; Sanders, Mark; Murphy, Caroline; Ejibe, Amaka; Milligan, Holly; Kelly, Joanna; Ambler, Gareth

2014-10-24

Longstanding complex regional pain syndrome (CRPS) is refractory to treatment with established analgesic drugs in most cases, and for many patients, alternative pain treatment approaches, such as with neuromodulation devices or rehabilitation methods, also do not work. The development of novel, effective treatment technologies is, therefore, important. There are preliminary data suggesting that low-dose immunoglobulin treatment may significantly reduce pain from longstanding CRPS. LIPS is a multicentre (United Kingdom), double-blind, randomised parallel group, placebo-controlled trial, designed to evaluate the efficacy, safety, and tolerability of intravenous immunoglobulin (IVIg) 0.5 g/kg plus standard treatment, versus matched placebo plus standard treatment in 108 patients with longstanding complex regional pain syndrome. Participants with moderate or severe CRPS of between 1 and 5 years duration will be randomly allocated to receive IVIg 0.5 g/kg (IntratectTM 50 g/l solution for infusion) or matching placebo administered day 1 and day 22 after randomisation, followed by two optional doses of open-label medication on day 43 after randomisation and on day 64 after randomisation. The primary outcome is the patients' pain intensity in the IVIG group compared with the placebo group, between 6 and 42 days after randomisation. The primary trial objective is to confirm the efficacy and confidently determine the effect size of the IVIG treatment technology in this group of patients. ISRCTN42179756 (Registered 28 June 13).

Fenoterol hydrobromide delivered via HFA-MDI or CFC-MDI in patients with asthma: a safety and efficacy comparison.

PubMed

Goldberg, J; Böhning, W; Schmidt, P; Freund, E

2000-10-01

The main objective of the study was to compare the long-term safety and tolerability of fenoterol hydrobromide delivered using a metered-dose inhaler formulated with the alternative propellant, hydrofluoroalkane 134a (HFA-MDI), with delivery using the currently available chlorofluorocarbon MDI (CFC-MDI; Berotec 100). A further objective was to compare the efficacy of fenoterol HFA-MDI with fenoterol CFC-MDI, using the pulmonary function parameters of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). Following a 2-week run-in phase, a 12-week, double-blind parallel group comparison was undertaken in 290 patients randomized on a 2:1 basis to two puffs of 100 microg fenoterol four times a day (HFA-MDI=197 patients; CFC-MDI=93 patients). A total of 236 patients in this multi-centre study completed the trial as planned. The overall incidence of adverse events (AEs) was similar in both groups (29.9% of HFA-MDI patients and 28% of CFC-MDI patients). Reports of respiratory disorder AEs were also comparable (21.8% HFA-MDI; 22.6% CFCMDI). End of study laboratory tests, ECG, pulse, blood pressure and physical examination showed no significant differences from pre-study baselines in either group and both treatments appeared to be well tolerated. Pre-dose FEV1 measurements taken at the three clinic visits were constant and increase in FEV1 at 5 and 30 min post-dose demonstrated equivalent efficacy for the two formulations. No difference between the two groups was observed in PEF or in the use of rescue medication. We conclude from these findings that the long-term safety and efficacy profile of fenoterol HFA-MDI is comparable to that of the fenoterol CFC-MDI.

Multicentre imaging measurements for oncology and in the brain

PubMed Central

Tofts, P S; Collins, D J

2011-01-01

Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (<2–3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B1 errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T1, diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion. PMID:22433831

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.

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial.

PubMed

Valery, Patricia C; Morris, Peter S; Byrnes, Catherine A; Grimwood, Keith; Torzillo, Paul J; Bauert, Paul A; Masters, I Brent; Diaz, Abbey; McCallum, Gabrielle B; Mobberley, Charmaine; Tjhung, Irene; Hare, Kim M; Ware, Robert S; Chang, Anne B

2013-10-01

Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1-2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12-24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35-0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study. National Health and Medical Research Council (Australia) and Health Research Council (New Zealand). Copyright © 2013 Elsevier Ltd. All rights reserved.

Euiiyin-tang in the treatment of obesity: study protocol for a randomised controlled trial.

PubMed

Cheon, Chunhoo; Jang, Soobin; Park, Jeong-Su; Ko, Youme; Kim, Doh Sun; Lee, Byung Hoon; Song, Hyun Jong; Song, Yun-Kyung; Jang, Bo-Hyoung; Shin, Yong-Cheol; Ko, Seong-Gyu

2017-06-21

Obesity is a public health concern in many countries due to its increasing prevalence. Euiiyin-tang is an herbal medicine formula often used as a clinical treatment for obesity. It acts to eliminate humidity and purify the blood, the causes of obesity identified by the theoretical framework of Korean medicine. The purpose of this study is to evaluate the efficacy and safety of Euiiyin-tang in treating obesity. This study is a randomised, double-blinded and placebo-controlled, multicentre trial. It has two parallel arms: the Euiiyin-tang group and the placebo group. A total of 160 obese adult women will be enrolled in the trial. The participants will be randomly divided at a 1:1 ratio at visit 2 (baseline). The participants will be administered Euiiyin-tang or placebo for 12 weeks. The primary endpoint is the change in weight occurring between baseline and post-treatment. The secondary outcomes include average weight reduction, changes in body fat, waist and hip circumferences, body mass index, and lipid profile, and the results of questionnaires such as the Korean version of Obesity-related Quality of Life, the Korean version of Eating Attitudes Test, the Social Readjustment Rating Scale, and the Stress Reaction Inventory. The present study will provide research methodologies for evaluating the efficacy and safety of Euiiyin-tang in patients with obesity. In addition, it will provide evidence of correlation between obesity and Sasang constitutional medicine. ClinicalTrials.gov, NCT01724099 . Registered on 2 November 2012.

Pelvic floor muscle training for secondary prevention of pelvic organ prolapse (PREVPROL): a multicentre randomised controlled trial.

PubMed

Hagen, Suzanne; Glazener, Cathryn; McClurg, Doreen; Macarthur, Christine; Elders, Andrew; Herbison, Peter; Wilson, Don; Toozs-Hobson, Philip; Hemming, Christine; Hay-Smith, Jean; Collins, Marissa; Dickson, Sylvia; Logan, Janet

2017-01-28

Pelvic floor muscle training can reduce prolapse severity and symptoms in women seeking treatment. We aimed to assess whether this intervention could also be effective in secondary prevention of prolapse and the need for future treatment. We did this multicentre, parallel-group, randomised controlled trial at three centres in New Zealand and the UK. Women from a longitudinal study of pelvic floor function after childbirth were potentially eligible for inclusion. Women of any age who had stage 1-3 prolapse, but had not sought treatment, were randomly assigned (1:1), via remote computer allocation, to receive either one-to-one pelvic floor muscle training (five physiotherapy appointments over 16 weeks, and annual review) plus Pilates-based pelvic floor muscle training classes and a DVD for home use (intervention group), or a prolapse lifestyle advice leaflet (control group). Randomisation was minimised by centre, parity (three or less vs more than three deliveries), prolapse stage (above the hymen vs at or beyond the hymen), and delivery method (any vaginal vs all caesarean sections). Women and intervention physiotherapists could not be masked to group allocation, but allocation was masked from data entry researchers and from the trial statistician until after database lock. The primary outcome was self-reported prolapse symptoms (Pelvic Organ Prolapse Symptom Score [POP-SS]) at 2 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01171846. Between Dec 21, 2008, and Feb 24, 2010, in New Zealand, and Oct 27, 2010, and Sept 5, 2011, in the UK, we randomly assigned 414 women to the intervention group (n=207) or the control group (n=207). One participant in each group was excluded after randomisation, leaving 412 women for analysis. At baseline, 399 (97%) women had prolapse above or at the level of the hymen. The mean POP-SS score at 2 years was 3·2 (SD 3·4) in the intervention group versus 4·2 (SD 4·4) in the control group (adjusted mean difference -1·01, 95% CI -1·70 to -0·33; p=0·004). The mean symptom score stayed similar across time points in the control group, but decreased in the intervention group. Three adverse events were reported, all of which were in the intervention group (one women had a fall, one woman had a pain in her tail bone, and one woman had chest pain and shortness of breath). Our study shows that pelvic floor muscle training leads to a small, but probably important, reduction in prolapse symptoms. This finding will be important for women and caregivers considering preventive strategies. Wellbeing of Women charity, the New Zealand Continence Association, and the Dean's Bequest Fund of Dunedin School of Medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe

PubMed Central

Kissling, Esther; Rondy, Marc

2017-01-01

We measured early 2016/17 season influenza vaccine effectiveness (IVE) against influenza A(H3N2) in Europe using multicentre case control studies at primary care and hospital levels. IVE at primary care level was 44.1%, 46.9% and 23.4% among 0–14, 15–64 and ≥ 65 year-olds, and 25.7% in the influenza vaccination target group. At hospital level, IVE was 2.5%, 7.9% and 2.4% among ≥ 65, 65–79 and ≥ 80 year-olds. As in previous seasons, we observed suboptimal IVE against influenza A(H3N2). PMID:28230524

Can access to spirometry in asthma education centres influence the referral rate by primary physicians for education?

PubMed Central

Labrecque, M; Lavallée, M; Beauchesne, MF; Cartier, A; Boulet, LP

2006-01-01

BACKGROUND AND OBJECTIVES: Asthma remains uncontrolled in a large number of asthmatic patients. Recent surveys have shown that a minority of asthmatic patients are referred to asthma educators. The objective of the present study was to assess the influence of increased access to spirometry in asthma education centres (AECs) on the rate of patient referrals to these centres by general practitioners. METHODS: A one-year, prospective, randomized, multicentric, parallel group study was conducted over two consecutive periods of six months each, with added spirometry being offered in the second six-month period to the experimental group. Ten AECs were enrolled in the project. An advertisement describing the AECs’ services was sent by mail to a total of 303 general practitioners at the start of each period, inviting them to refer their patients. Measures of the frequency of medical referrals to the AECs were assessed for each period. RESULTS: The group of AECs randomly selected for spirometry in the second six-month period received 48 medical referrals during the first period and 32 during the second one, following proposed spirometry. AECs that had not offered spirometry received five referrals during the first period and seven during the second period. One AEC withdrew a few weeks after the study began and others encountered administrative problems, reducing their ability to provide interventions. CONCLUSIONS: Referral to AECs is not yet integrated into the primary care of asthma and offering more rapid access to spirometry in the AECs does not seem to be a significant incentive for such referrals. PMID:17149461

Can access to spirometry in asthma education centres influence the referral rate by primary physicians for education?

PubMed

Labrecque, M; Lavallée, M; Beauchesne, M F; Cartier, A; Boulet, L P

2006-01-01

Asthma remains uncontrolled in a large number of asthmatic patients. Recent surveys have shown that a minority of asthmatic patients are referred to asthma educators. The objective of the present study was to assess the influence of increased access to spirometry in asthma education centres (AECs) on the rate of patient referrals to these centres by general practitioners. A one-year, prospective, randomized, multicentric, parallel group study was conducted over two consecutive periods of six months each, with added spirometry being offered in the second six-month period to the experimental group. Ten AECs were enrolled in the project. An advertisement describing the AECs' services was sent by mail to a total of 303 general practitioners at the start of each period, inviting them to refer their patients. Measures of the frequency of medical referrals to the AECs were assessed for each period. The group of AECs randomly selected for spirometry in the second six-month period received 48 medical referrals during the first period and 32 during the second one, following proposed spirometry. AECs that had not offered spirometry received five referrals during the first period and seven during the second period. One AEC withdrew a few weeks after the study began and others encountered administrative problems, reducing their ability to provide interventions. Referral to AECs is not yet integrated into the primary care of asthma and offering more rapid access to spirometry in the AECs does not seem to be a significant incentive for such referrals.

Outcome of Heart Failure with Preserved Ejection Fraction: A Multicentre Spanish Registry

PubMed Central

Castillo, Juan C; Anguita1, Manuel P; Jiménez, Manuel

2009-01-01

Background: Studies on clinical features, treatment and prognosis of patients with congestive heart failure (CHF) and preserved left ventricular ejection fraction (LVEF) are few and their results frequently conflicting. Aims: To investigate the characteristics and long term prognosis of patients with CHF and preserved (≥ 45%) LVEF. Methods and Results: We conducted a prospective multicentre study with 4720 patients attended in 62 heart failure clinics from 1999 to 2003 in Spain (BADAPIC registry). LVEF was preserved in 30% patients. Age, female gender, prevalence of atrial fibrillation, hypertension and non-ischaemic cardiopathy were all significantly greater in patients with preserved LVEF. Mean follow-up was 40±12 months. Mortality and other cardiovascular complication rates during follow up were similar in both groups. On multivariate analysis ejection fraction was not an independent predictor for mortality. Survival at one and five years was similar in both groups (79% and 59% for patients with preserved LVEF and 78% and 57% for those with reduced LVEF, respectively). Conclusions: In the BADAPIC registry, a high percentage of heart failure patients had preserved LVEF. Although clinical differences were seen between groups, morbidity and mortality were similar in both groups. PMID:21037850

Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

PubMed

Mohanty, D; Colah, R B; Gorakshakar, A C; Patel, R Z; Master, D C; Mahanta, J; Sharma, S K; Chaudhari, U; Ghosh, M; Das, S; Britt, R P; Singh, S; Ross, C; Jagannathan, L; Kaul, R; Shukla, D K; Muthuswamy, V

2013-01-01

The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA(2), HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of β-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of β-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δβ-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE β-thalassemia as well as HbS homozygous and HbS-β-thalassemia (<1 %) were also identified. This is the first large multicentre study covering cities from different regions of the country for screening for β-thalassemia carriers and other haemoglobinopathies where uniform protocols and methodology was followed and quality control ensured by the co-ordinating centre. This study also shows that establishment of centres for screening for β-thalassemia and other haemoglobinopathies is possible in medical colleges. Creating awareness, screening and counselling can be done at these centres. This experience will help to formulate a national thalassemia control programme in India.

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/

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series

PubMed Central

Taylor, Morag A; Reilly, David; Llewellyn-Jones, Robert H; McSharry, Charles; Aitchison, Tom C

2000-01-01

Objective 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. Design Randomised, double blind, placebo controlled, parallel group, multicentre study. Setting Four general practices and a hospital ear, nose, and throat outpatient department. Participants 51 patients with perennial allergic rhinitis. Intervention Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. Main outcome measures Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. Results 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). Conclusion The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo. PMID:10948025

Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.

PubMed

Boden, Ianthe; Skinner, Elizabeth H; Browning, Laura; Reeve, Julie; Anderson, Lesley; Hill, Cat; Robertson, Iain K; Story, David; Denehy, Linda

2018-01-24

To assess the efficacy of a single preoperative physiotherapy session to reduce postoperative pulmonary complications (PPCs) after upper abdominal surgery. Prospective, pragmatic, multicentre, patient and assessor blinded, parallel group, randomised placebo controlled superiority trial. Multidisciplinary preadmission clinics at three tertiary public hospitals in Australia and New Zealand. 441 adults aged 18 years or older who were within six weeks of elective major open upper abdominal surgery were randomly assigned through concealed allocation to receive either an information booklet (n=219; control) or preoperative physiotherapy (n=222; intervention) and followed for 12 months. 432 completed the trial. Preoperatively, participants received an information booklet (control) or an additional 30 minute physiotherapy education and breathing exercise training session (intervention). Education focused on PPCs and their prevention through early ambulation and self directed breathing exercises to be initiated immediately on regaining consciousness after surgery. Postoperatively, all participants received standardised early ambulation, and no additional respiratory physiotherapy was provided. The primary outcome was a PPC within 14 postoperative hospital days assessed daily using the Melbourne group score. Secondary outcomes were hospital acquired pneumonia, length of hospital stay, utilisation of intensive care unit services, and hospital costs. Patient reported health related quality of life, physical function, and post-discharge complications were measured at six weeks, and all cause mortality was measured to 12 months. The incidence of PPCs within 14 postoperative hospital days, including hospital acquired pneumonia, was halved (adjusted hazard ratio 0.48, 95% confidence interval 0.30 to 0.75, P=0.001) in the intervention group compared with the control group, with an absolute risk reduction of 15% (95% confidence interval 7% to 22%) and a number needed to treat of 7 (95% confidence interval 5 to 14). No significant differences in other secondary outcomes were detected. In a general population of patients listed for elective upper abdominal surgery, a 30 minute preoperative physiotherapy session provided within existing hospital multidisciplinary preadmission clinics halves the incidence of PPCs and specifically hospital acquired pneumonia. Further research is required to investigate benefits to mortality and length of stay. Australian New Zealand Clinical Trials Registry ANZCTR 12613000664741. 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.

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.

A comparison of the clinical effectiveness and cost of specialised individually delivered parent training for preschool attention-deficit/hyperactivity disorder and a generic, group-based programme: a multi-centre, randomised controlled trial of the New Forest Parenting Programme versus Incredible Years.

PubMed

Sonuga-Barke, Edmund J S; Barton, Joanne; Daley, David; Hutchings, Judy; Maishman, Tom; Raftery, James; Stanton, Louise; Laver-Bradbury, Cathy; Chorozoglou, Maria; Coghill, David; Little, Louisa; Ruddock, Martin; Radford, Mike; Yao, Guiqing Lily; Lee, Louise; Gould, Lisa; Shipway, Lisa; Markomichali, Pavlina; McGuirk, James; Lowe, Michelle; Perez, Elvira; Lockwood, Joanna; Thompson, Margaret J J

2018-06-01

The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.

[Multicentric prospective randomized and controlled study assessing effectiveness of intravaginal electrostimulation at home compared to usual care in female patients with urinary incontinence and prior perineal reeducation].

PubMed

Lopès, P; Rimbault, F; Scheffler, M; André, C; Cappelletti, M-C; Marès, P

2014-11-01

In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported as worsened in 16.5% of the UC group. Using GYNEFFIK(®) favorably impacts quality of life, particularly physical activity and vitality and decreases emotional consequences of UI (i.e. anxiety and depression score as assessed by HAD scale). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The effectiveness of 2-implant overdentures - a pragmatic international multicentre study.

PubMed

Rashid, F; Awad, M A; Thomason, J M; Piovano, A; Spielberg, G P; Scilingo, E; Mojon, P; Müller, F; Spielberg, M; Heydecke, G; Stoker, G; Wismeijer, D; Allen, F; Feine, J S

2011-03-01

The purpose of this multicentre observational study was to determine patient satisfaction with either conventional dentures or mandibular 2-implant overdentures in a 'real world' setting. Two hundred and three edentulous patients (mean age 68·8 ± 10·4 years) were recruited at eight centres located in North America, South America and Europe. The patients were provided with new mandibular conventional dentures or implant overdentures supported by two implants and ball attachments. At baseline and at 6 months post-treatment, they rated their satisfaction with their mandibular prostheses on 100-mm visual analogue scale questionnaires. One hundred and two (50·2%) participants had valid baseline and 6-month satisfaction data. Although both groups reported improvements, the implant overdenture group reported significantly higher ratings of overall satisfaction, comfort, stability, ability to speak and ability to chew. These results suggest that edentulous patients who choose mandibular implant overdentures have significantly greater improvements in satisfaction, despite their relatively higher cost, than those who choose new conventional dentures. © 2010 Blackwell Publishing Ltd.

Imaging biomarker roadmap for cancer studies

PubMed Central

O’Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; deSouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, John R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

2017-01-01

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

PubMed

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-12-21

Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

Effects of an alert system on implantable cardioverter defibrillator-related anxiety: rationale, design, and endpoints of the PANORAMIC multicentre trial.

PubMed

Duru, Firat; Dorian, Paul; Favale, Stefano; Perings, Christian; Pedersen, Susanne S; Willems, Vincent

2010-05-01

Implantable cardioverter defibrillators (ICD) can prevent sudden cardiac death by delivering high-energy shocks in patients at risk of life-threatening ventricular tachyarrhythmias. Patients may be anxious about receiving inappropriate shocks in case of device or lead system malfunction, or about failing to receive needed therapy for the same reason. New devices include programmable vibrating patient notifiers (PN), which, by warning patients of a possible device dysfunction, might lower device-related anxiety. PAtient NOtifier feature for Reduction of Anxiety: a Multicentre ICD study (PANORAMIC) is a multicentre, randomized, clinical trial designed to examine the effects of the awareness of an active vibrating alert system on device-related anxiety. The trial will randomly assign 356 patients in a 1:1 design to a control group (PN OFF) vs. a treatment group (PN ON). Patients will be followed for 12 months, with visits scheduled at 6 and 12 months. During clinical follow-up visits, the ICD will be interrogated, and all patients will complete the Hospital Anxiety and Depression Scale and a device-related anxiety questionnaire. The sensitivity and specificity of PN, the effect of personality on anxiety, using the Type D scale (DS14), the number of delivered appropriate and inappropriate ICD therapies, changes in anxiety related to the delivery of appropriate or inappropriate shocks, crossovers from the assigned group, the number of hospitalizations, and the mortality rate will also be assessed. ClinicalTrials.gov Identifier: NCT00559559.

Treatment of chronic diabetic lower extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi-centre comparative study examining clinical efficacy and cost.

PubMed

Zelen, Charles M; Serena, Thomas E; Gould, Lisa; Le, Lam; Carter, Marissa J; Keller, Jennifer; Li, William W

2016-04-01

Advanced therapies such as bioengineered skin substitutes (BSS) and dehydrated human amnion/chorion membrane (dHACM) have been shown to promote healing of chronic diabetic ulcers. An interim analysis of data from 60 patients enrolled in a prospective, randomised, controlled, parallel group, multi-centre clinical trial showed that dHACM (EpiFix, MiMedx Group Inc., Marietta, GA) is superior to standard wound care (SWC) and BSS (Apligraf, Organogenesis, Inc., Canton, MA) in achieving complete wound closure within 4-6 weeks. Rates and time to closure at a longer time interval and factors influencing outcomes remained unassessed; therefore, the study was continued in order to achieve at least 100 patients. With the larger cohort, we compare clinical outcomes at 12 weeks in 100 patients with chronic lower extremity diabetic ulcers treated with weekly applications of Apligraf (n = 33), EpiFix (n = 32) or SWC (n = 35) with collagen-alginate dressing as controls. A Cox regression was performed to analyse the time to heal within 12 weeks, adjusting for all significant covariates. A Kaplan-Meier analysis was conducted to compare time-to-heal within 12 weeks for the three treatment groups. Clinical characteristics were well matched across study groups. The proportion of wounds achieving complete closure within the 12-week study period were 73% (24/33), 97% (31/32), and 51% (18/35) for Apligraf, EpiFix and SWC, respectively (adjusted P = 0·00019). Subjects treated with EpiFix had a very significant higher probability of their wounds healing [hazard ratio (HR: 5·66; adjusted P: 1·3 x 10(-7) ] compared to SWC alone. No difference in probability of healing was observed for the Apligraf and SWC groups. Patients treated with Apligraf were less likely to heal than those treated with EpiFix [HR: 0·30; 95% confidence interval (CI): 0·17-0·54; unadjusted P: 5·8 x 10(-5) ]. Increased wound size and presence of hypertension were significant factors that influenced healing. Mean time-to-heal within 12 weeks was 47·9 days (95% CI: 38·2-57·7) with Apligraf, 23·6 days (95% CI: 17·0-30·2) with EpiFix group and 57·4 days (95%CI: 48·2-66·6) with the SWC alone group (adjusted P = 3·2 x 10(-7) ). Median number of grafts used per healed wound were six (range 1-13) and 2·5 (range 1-12) for the Apligraf and EpiFix groups, respectively. Median graft cost was $8918 (range $1,486-19,323) per healed wound for the Apligraf group and $1,517 (range $434-25,710) per healed wound in the EpiFix group (P < 0·0001). These results provide further evidence of the clinical and resource utilisation superiority of EpiFix compared to Apligraf for the treatment of lower extremity diabetic wounds. © 2015 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Implementation of evidence-based weekend service recommendations for allied health managers: a cluster randomised controlled trial protocol.

PubMed

Sarkies, Mitchell N; White, Jennifer; Morris, Meg E; Taylor, Nicholas F; Williams, Cylie; O'Brien, Lisa; Martin, Jenny; Bardoel, Anne; Holland, Anne E; Carey, Leeanne; Skinner, Elizabeth H; Bowles, Kelly-Ann; Grant, Kellie; Philip, Kathleen; Haines, Terry P

2018-04-24

It is widely acknowledged that health policy and practice do not always reflect current research evidence. Whether knowledge transfer from research to practice is more successful when specific implementation approaches are used remains unclear. A model to assist engagement of allied health managers and clinicians with research implementation could involve disseminating evidence-based policy recommendations, along with the use of knowledge brokers. We developed such a model to aid decision-making for the provision of weekend allied health services. This protocol outlines the design and methods for a multi-centre cluster randomised controlled trial to evaluate the success of research implementation strategies to promote evidence-informed weekend allied health resource allocation decisions, especially in hospital managers. This multi-centre study will be a three-group parallel cluster randomised controlled trial. Allied health managers from Australian and New Zealand hospitals will be randomised to receive either (1) an evidence-based policy recommendation document to guide weekend allied health resource allocation decisions, (2) the same policy recommendation document with support from a knowledge broker to help implement weekend allied health policy recommendations, or (3) a usual practice control group. The primary outcome will be alignment of weekend allied health service provision with policy recommendations. This will be measured by the number of allied health service events (occasions of service) occurring on weekends as a proportion of total allied health service events for the relevant hospital wards at baseline and 12-month follow-up. Evidence-based policy recommendation documents communicate key research findings in an accessible format. This comparatively low-cost research implementation strategy could be combined with using a knowledge broker to work collaboratively with decision-makers to promote knowledge transfer. The results will assist managers to make decisions on resource allocation, based on evidence. More generally, the findings will inform the development of an allied health model for translating research into practice. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) ( ACTRN12618000029291 ). Universal Trial Number (UTN): U1111-1205-2621.

Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis.

PubMed

Xu, Jane; Liu, Yingrui Cyril; Adams, Susan; Karpelowsky, Jonathan

2016-12-21

This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ 2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. NCT02795793; ACTRN12616000788471. 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/.

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

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).

Counselling by primary care physicians may help patients with heartburn-predominant uninvestigated dyspepsia.

PubMed

Paré, Pierre; Lee, Joanna; Hawes, Ian A

2010-03-01

To determine whether strategies to counsel and empower patients with heartburn-predominant dyspepsia could improve health-related quality of life. Using a cluster randomized, parallel group, multicentre design, nine centres were assigned to provide either basic or comprehensive counselling to patients (age range 18 to 50 years) presenting with heartburn-predominant upper gastrointestinal symptoms, who would be considered for drug therapy without further investigation. Patients were treated for four weeks with esomeprazole 40 mg once daily, followed by six months of treatment that was at the physician's discretion. The primary end point was the baseline change in Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire score. A total of 135 patients from nine centres were included in the intention-to-treat analysis. There was a statistically significant baseline improvement in all domains of the QOLRAD questionnaire in both study arms at four and seven months (P<0.0001). After four months, the overall mean change in QOLRAD score appeared greater in the comprehensive counselling group than in the basic counselling group (1.77 versus 1.47, respectively); however, this difference was not statistically significant (P=0.07). After seven months, the overall mean baseline change in QOLRAD score between the comprehensive and basic counselling groups was not statistically significant (1.69 versus 1.56, respectively; P=0.63). A standardized, comprehensive counselling intervention showed a positive initial trend in improving quality of life in patients with heartburn-predominant uninvestigated dyspepsia. Further investigation is needed to confirm the potential benefits of providing patients with comprehensive counselling regarding disease management.

Counselling by primary care physicians may help patients with heartburn-predominant uninvestigated dyspepsia

PubMed Central

Paré, Pierre; Math, Joanna Lee M; Hawes, Ian A

2010-01-01

OBJECTIVE: To determine whether strategies to counsel and empower patients with heartburn-predominant dyspepsia could improve health-related quality of life. METHODS: Using a cluster randomized, parallel group, multicentre design, nine centres were assigned to provide either basic or comprehensive counselling to patients (age range 18 to 50 years) presenting with heartburn-predominant upper gastrointestinal symptoms, who would be considered for drug therapy without further investigation. Patients were treated for four weeks with esomeprazole 40 mg once daily, followed by six months of treatment that was at the physician’s discretion. The primary end point was the baseline change in Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire score. RESULTS: A total of 135 patients from nine centres were included in the intention-to-treat analysis. There was a statistically significant baseline improvement in all domains of the QOLRAD questionnaire in both study arms at four and seven months (P<0.0001). After four months, the overall mean change in QOLRAD score appeared greater in the comprehensive counselling group than in the basic counselling group (1.77 versus 1.47, respectively); however, this difference was not statistically significant (P=0.07). After seven months, the overall mean baseline change in QOLRAD score between the comprehensive and basic counselling groups was not statistically significant (1.69 versus 1.56, respectively; P=0.63). CONCLUSIONS: A standardized, comprehensive counselling intervention showed a positive initial trend in improving quality of life in patients with heartburn-predominant uninvestigated dyspepsia. Further investigation is needed to confirm the potential benefits of providing patients with comprehensive counselling regarding disease management. PMID:20352148

Two-year study of relapse prevention by a new education program in schizophrenic patients treated with the same antipsychotic drug.

PubMed

Chabannes, Jean-Paul; Bazin, Nadine; Leguay, Denis; Nuss, Philippe; Peretti, Charles-Siegfried; Tatu, Patrick; Hameg, Ahcene; Garay, Ricardo P; Ferreri, Maurice

2008-01-01

It is not clear whether patient's psycho-education enhances compliance to antipsychotic treatments and reduces the number of relapses. Here we investigated the impact of a new psycho-educational program (SOLEDUC) on the one- and two-years rate of relapse (primary outcome measure) and a number of clinical assessments (secondary outcome measures). This was a multicentric French clinical trial (51 centers) of Phase IV, open, controlled, randomized, consisting in two parallel groups: the Soleduc group (N=111) and the control group (N=109). All subjects received a variable dose over the 2-year period of the same antipsychotic drug (amisulpride). Soleduc consisted of a 7-session program (1h per session), presented three times (at baseline, 6-months and 12-months). Patients in the control group received a non-specific psychosocial training for an equivalent period of time. The models of Andersen-Gill (AG) and Prentice, Williams and Peterson (PWP) were used to analyze relapses. Patients in the Soleduc group attended 14.8+/-6.1 sessions (mean+/-SD), including 17 patients who never attended a session. Intent to treat analysis showed less patients relapsing in the Soleduc group as compared to the control group (21.6% versus 28.4% after 1 year and 84.4% versus 90.8% after 2years), but the differences were not statistically significant. Relapse risk was significantly reduced for patients who followed at least 7 modules (p=0.015 AG-test; p<0.001 PWP-test). In conclusion, no significant differences in relapse rates were found between patients attending the Soleduc program and the control group. Attendance of at least 7 out of 21 program sessions was required to see a modest, but significant two-year relapse prevention in schizophrenia. Other well designed studies are required to evaluate the medical impact of patient's education programs.

Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

PubMed

Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

2014-03-01

Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy and safety of a selective α1 -adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial.

PubMed

2015-06-13

The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the effect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18-75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registered with ClinicalTrials.gov, number NCT01149590. Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassified the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; p<0·0001). Although both the certainty (relative risk [RR] 2·56, 95% CI 2·33-2·79; p<0·0001) and frequency of coronary heart disease increased (1·09, 1·02-1·17; p=0·0172), the certainty increased (1·79, 1·62-1·96; p<0·0001) and frequency seemed to decrease (0·93, 0·85-1·02; p=0·1289) for the diagnosis of angina due to coronary heart disease. This changed planned investigations (15% vs 1%; p<0·0001) and treatments (23% vs 5%; p<0·0001) but did not affect 6-week symptom severity or subsequent admittances to hospital for chest pain. After 1·7 years, CTCA was associated with a 38% reduction in fatal and non-fatal myocardial infarction (26 vs 42, HR 0·62, 95% CI 0·38-1·01; p=0·0527), but this was not significant. In patients with suspected angina due to coronary heart disease, CTCA clarifies the diagnosis, enables targeting of interventions, and might reduce the future risk of myocardial infarction. The Chief Scientist Office of the Scottish Government Health and Social Care Directorates funded the trial with supplementary awards from Edinburgh and Lothian's Health Foundation Trust and the Heart Diseases Research Fund. Copyright © 2015 Newby et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs.

PubMed

Benchaoui, H A; Siedek, E M; De La Puente-Redondo, V A; Tilt, N; Rowan, T G; Clemence, R G

2007-09-29

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).

The effects and safety of dexibuprofen compared with ibuprofen in febrile children caused by upper respiratory tract infection

PubMed Central

Yoon, Jong Seo; Jeong, Dae-Chul; Oh, Jae-Won; Lee, Keun Young; Lee, Hyun Seung; Koh, Young Yull; Kim, Jin Tack; Kang, Jin Han; Lee, Joon Sung

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTThe analgesic and anti-inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain. WHAT THIS STUDY ADDSDexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children. AIM To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI). METHODS The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer-based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group. RESULTS In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups (P > 0.05). There also was no significant difference in adverse drug reaction (P > 0.05). CONCLUSIONS Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children. PMID:19032727

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma

PubMed Central

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-01-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma. PMID:26933263

Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma.

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-03-01

Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.

Maintenance Cognitive Stimulation Therapy (CST) for dementia: A single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia

PubMed Central

2010-01-01

Background Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. Methods/Design This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks. The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. Discussion A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors. Trial Registration ISRCTN26286067 PMID:20426866

Maintenance Cognitive Stimulation Therapy (CST) for dementia: a single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia.

PubMed

Aguirre, Elisa; Spector, Aimee; Hoe, Juanita; Russell, Ian T; Knapp, Martin; Woods, Robert T; Orrell, Martin

2010-04-28

Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks.The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors.

Efficacy and tolerability of a new synergized pyrethrins thermofobic foam in comparison with benzyl benzoate in the treatment of scabies in convicts: the ISAC study (Studio Della scabbia in ambiente carcerario).

PubMed

Biele, M; Campori, G; Colombo, R; De Giorgio, G; Frascione, P; Sali, R; Starnini, G; Milani, M

2006-07-01

Scabies is a very common skin infection in convicts. The SIMSPE Society (Società Italiana di Medicina e Sanità Penitenziaria) has organized and conducted a multicentre, randomized, comparative, parallel group, investigator-blinded trial to evaluate the efficacy and tolerability of synergized pyrethrins foam (PF) in comparison with benzyl benzoate (BB) lotion. A total of 240 convicted patients, enrolled in eight National Jail Institutions, with a clinical diagnosis of scabies, were treated with PF (n = 120) for three consecutive days or BB (n = 120) for five consecutive days. Primary study endpoints were the clinical cure rate and the local tolerability. Secondary endpoints were clinical evolution of scabietic lesions and itching intensity. Study outcomes were assessed using appropriate semiquantitative scores at baseline and after 2 and 4 weeks. A second treatment cycle was applied if after 2 weeks the patient was not judged clinically cured. At week 2, a total of 75% (95% CI: 66-82%) and 71% (95% CI: 62-78%) of patients showed a complete clinical cure rate in the PF and BB groups, respectively. At week 4, the percentage of totally cured patients increased up to 95% (95% CI: 89-97%) and 91% (95% CI: 83-94%) in the PF and BB groups, respectively (P = NS between groups). At week 4, 5% in the PF group and 9% in the BB group complained of itching. Burning and irritation after treatment applications were more common in the BB group in comparison with the PF group. The tolerability score was better in the PF group in comparison with to BB group (2.9 vs. 2.2; P = 0.0001). A total of 95% of patients in the PV group had a good tolerability score (i.e. = 3) in comparison with 41% in the BB group. Our results show that a 3-day treatment with pyrethrins thermofobic foam is at least as effective as a 5-day treatment with benzyl benzoate lotion in convicted subjects with scabies. The foam formulation is better tolerated than the benzyl benzoate lotion.

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

PubMed Central

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-01-01

Introduction Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. Trial registration number ACTRN12614000418673, Pre-results. PMID:27932335

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH).

PubMed

Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc

2018-06-22

Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial

PubMed Central

Ross, J D C; Cronjé, H S; Paszkowski, T; Rakoczi, I; Vildaite, D; Kureishi, A; Alefelder, M; Arvis, P; Reimnitz, P

2006-01-01

Objective This multinational, multicentre, prospective, randomised, double blind, parallel group, non‐inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease. Methods Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin, 400 mg once daily (n = 384), or oral ofloxacin, 400 mg twice daily plus oral metronidazole, 500 mg twice daily (n = 365). Results Of the 741 patients in the intent to treat (ITT) population, 564 (74.2%) were valid for the per protocol (PP) analyses; 112 (19.9%) of these were included in the microbiologically valid population (MBV). Clinical resolution rates in the PP population at the test of cure visit (TOC, 5–24 days post‐therapy, primary efficacy end point) were 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI: −5.7% to 4.0%). At follow up (28–42 days post‐therapy), resolution rates in the PP population were 85.8% (236/275) and 87.9% (254/289) for moxifloxacin and comparator, respectively (95% CI: −8.0% to 3.1%). Bacteriological success rates in the MBV population at TOC were 87.5% (49/56) for moxifloxacin and 82.1% (46/56) for comparator (95% CI: −8.3% to 18.8%). Against Chlamydia trachomatis and Neisseria gonorrhoeae, bacteriological success rates with moxifloxacin were 88.5% (23/26) and 100% (13/13) and for comparator 85.7% (18/21) and 81.8% (18/22), respectively. Drug related adverse events occurred less frequently with moxifloxacin (22.5% (85/378)) versus the comparator (30.9% (112/363)) (p = 0.01). Conclusion In uncomplicated PID, once daily moxifloxacin monotherapy was clinically and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events. PMID:16723364

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

PubMed Central

Döbrönte, Zoltán; Szepes, Zoltán; Izbéki, Ferenc; Gervain, Judit; Lakatos, László; Pécsi, Gyula; Ihász, Miklós; Lakner, Lilla; Toldy, Erzsébet; Czakó, László

2014-01-01

AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. METHODS: A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. RESULTS: Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. CONCLUSION: 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis. PMID:25110443

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

PubMed

Döbrönte, Zoltán; Szepes, Zoltán; Izbéki, Ferenc; Gervain, Judit; Lakatos, László; Pécsi, Gyula; Ihász, Miklós; Lakner, Lilla; Toldy, Erzsébet; Czakó, László

2014-08-07

To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

Topical Olive Oil Is Not Inferior to Hyperoxygenated Fatty Aids to Prevent Pressure Ulcers in High-Risk Immobilised Patients in Home Care. Results of a Multicentre Randomised Triple-Blind Controlled Non-Inferiority Trial

PubMed Central

2015-01-01

Pressure ulcers represent a major current health problem and produce an important economic impact on the healthcare system. Most of studies to prevent pressure ulcers have been carried out in hospital contexts, with respect to the use of hyperoxygenated fatty acids and to date, no studies have specifically examined the use of olive oil-based substances. Methods and Design Main objective: To assess the effectiveness of the use of olive oil, comparing it with hyperoxygenated fatty acids, for immobilised home-care patients at risk of suffering pressure ulcers. Design: Non-inferiority, triple-blind, parallel, multicentre, randomised clinical trial. Scope: Population attending Primary Healthcare Centres in Andalusia (Spain). Sample: 831 immobilised patients at risk of suffering pressure ulcers. Results The follow-up period was 16 weeks. Groups were similar after randomization. In the per protocol analysis, none of the body areas evaluated presented risk differences for pressure ulcers incidence that exceeded the 10% delta value established. Sacrum: Olive Oil 8 (2.55%) vs HOFA 8 (3.08%), ARR 0.53 (-2.2 to 3.26) Right heel: Olive Oil 4 (1.27%) vs HOFA 5 (1.92)%, ARR0.65 (-1.43 to 2.73). Left heel: Olive Oil 3 (0.96%) vs HOFA 3 (1.15%), ARR0.2 (-1.49 to 1.88). Right trochanter: Olive Oil 0 (0%) vs HOFA 4 (1.54%), ARR1.54 (0.04 to 3.03). Left trochanter: Olive Oil 1 (0.32%) vs HOFA 1 (0.38%), ARR0.07 (-0.91 to 1.04). In the intention to treat analysis the lower limit of the established confidence interval was never exceeded. Discussion The results obtained confirmed that the use of topical extra-virgin olive oil to prevent PU in the home environment, for immobilised patients at high risk, is not inferior to the use of HOFA. Further studies are needed to investigate the mechanism by which olive oil achieves this outcome. Trial Registration Clinicaltrials.gov NCT01595347 PMID:25886152

Protocol of a multi-centre randomised controlled trial of a web-based information intervention with nurse-delivered telephone support for haematological cancer patients and their support persons.

PubMed

Bryant, Jamie; Sanson-Fisher, Rob; Stevenson, William; Smits, Rochelle; Henskens, Frans; Wei, Andrew; Tzelepis, Flora; D'Este, Catherine; Paul, Christine; Carey, Mariko

2015-04-17

High rates of anxiety, depression and unmet needs are evident amongst haematological cancer patients undergoing treatment and their Support Persons. Psychosocial distress may be minimised by ensuring that patients are sufficiently involved in decision making, provided with tailored information and adequate preparation for potentially threatening procedures. To date, there are no published studies evaluating interventions designed to reduce psychosocial distress and unmet needs specifically in patients with haematological cancers and their Support Persons. This study will examine whether access to a web-based information tool and nurse-delivered telephone support reduces depression, anxiety and unmet information needs for haematological cancer patients and their Support Persons. A non-blinded, parallel-group, multi-centre randomised controlled trial will be conducted to compare the effectiveness of a web-based information tool and nurse-delivered telephone support with usual care. Participants will be recruited from the haematology inpatient wards of five hospitals in New South Wales, Australia. Patients diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, Burkitt's lymphoma, Lymphoblastic lymphoma (B or T cell), or Diffuse Large B-Cell lymphoma and their Support Persons will be eligible to participate. Patients and their Support Persons will be randomised as dyads. Participants allocated to the intervention will receive access to a tailored web-based tool that provides accurate, up-to-date and personalised information about: cancer and its causes; treatment options including treatment procedures information; complementary and alternative medicine; and available support. Patients and Support Persons will complete self-report measures of anxiety, depression and unmet needs at 2, 4, 8 and 12 weeks post-recruitment. Patient and Support Person outcomes will be assessed independently. This study will assess whether providing information and support using web-based and telephone support address the major psychosocial challenges faced by haematological patients and their Support Persons. The approach, if found to be effective, has potential to improve psychosocial outcomes for haematological and other cancer patients, reduce the complexity and burden of meeting patients' psychosocial needs for health care providers with high potential for translation into clinical practice. ACTRN12612000720819.

Comparative assessment of the efficacy and safety of sertaconazole (2%) cream versus terbinafine cream (1%) versus luliconazole (1%) cream in patients with dermatophytoses: a pilot study.

PubMed

Jerajani, Hr; Janaki, C; Kumar, Sharath; Phiske, Meghana

2013-01-01

Sertaconazole is a new, broad spectrum, fungicidal and fungistatic imidazole with added antipruritic and anti-inflammatory activity that would provide greater symptomatic relief and hence would be beneficial in improving the quality of life for the patient with dermatophytoses. To compare efficacy and safety of sertaconazole, terbinafine and luliconazole in patients with dermatophytoses. 83 patients with tinea corporis and tinea cruris infections were enrolled in this multicentre, randomized, open label parallel study. The initial 'Treatment Phase' involved three groups receiving either sertaconazole 2% cream applied topically twice daily for four weeks, terbinafine 1% cream once daily for two weeks, luliconazole 1% cream once daily for two weeks. At the end of treatment phase, there was a 'Follow-up Phase' at end of 2 weeks, where the patients were assessed clinically and mycologically for relapse. Of the 83 patients, 62 completed the study, sertaconazole (n = 20), terbinafine (n = 22) and luliconazole (n = 20). The primary efficacy variables including change in pruritus, erythema, vesicle, desquamation and mycological cure were significantly improved in all the three groups, as compared to baseline, in the Treatment and Follow-up phase. Greater proportion of patients in sertaconazole group (85%) showed resolution of pruritus as compared to terbinafine (54.6%); and luliconazole (70%), (P < 0.05 sertaconazole vs terbinafine). There was a greater reduction in mean total composite score (pruritus, erythema, vesicle and desquamation) in sertaconazole group (97.1%) as compared to terbinafine (91.2%) and luliconazole (92.9%). All groups showed equal negative mycological assessment without any relapses. All three study drugs were well tolerated. Only one patient in sertaconazole group withdrew from the study due to suspected allergic contact dermatitis. Sertaconazole was better than terbinafine and luliconazole in relieving signs and symptoms during study and follow up period. At the end of 'Treatment Phase' and 'Follow-up' Phase, all patients showed negative mycological assessment in all three treatment groups suggesting no recurrence of the disease.

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/

ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA.

PubMed

Francesconi, Carlos Fernando de Magalhães; Machado, Marta Brenner; Steinwurz, Flavio; Nones, Rodrigo Bremer; Quilici, Flávio Antonio; Catapani, Wilson Roberto; Miszputen, Sender Jankiel; Bafutto, Mauro

2016-01-01

Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

PubMed

Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

2017-06-01

Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p < 0.001). High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed Central

1984-01-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide. PMID:6383234

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed

1984-08-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide.

Trauma airway management in emergency departments: a multicentre, prospective, observational study in Japan.

PubMed

Nakao, Shunichiro; Kimura, Akio; Hagiwara, Yusuke; Hasegawa, Kohei

2015-02-04

Although successful airway management is essential for emergency trauma care, comprehensive studies are limited. We sought to characterise current trauma care practice of airway management in the emergency departments (EDs) in Japan. Analysis of data from a prospective, observational, multicentre registry-the Japanese Emergency Airway Network (JEAN) registry. 13 academic and community EDs from different geographic regions across Japan. 723 trauma patients who underwent emergency intubation from March 2010 through August 2012. ED characteristics, patient and operator demographics, methods of airway management, intubation success or failure at each attempt and adverse events. A total of 723 trauma patients who underwent emergency intubation were eligible for the analysis. Traumatic cardiac arrest comprised 32.6% (95% CI 29.3% to 36.1%) of patients. Rapid sequence intubation (RSI) was the initial method chosen in 23.9% (95% CI 21.0% to 27.2%) of all trauma patients and in 35.5% (95% CI 31.4% to 39.9%) of patients without cardiac arrest. Overall, intubation was successful in ≤3 attempts in 96% of patients (95% CI 94.3% to 97.2%). There was a wide variation in the initial methods of intubation; RSI as the initial method was performed in 0-50.9% of all trauma patients among 12 EDs. Similarly, there was a wide variation in success rates and adverse event rates across the EDs. Success rates varied between 35.5% and 90.5% at the first attempt, and 85.1% and 100% within three attempts across the 12 EDs. In this multicentre prospective study in Japan, we observed a high overall success rate in airway management during trauma care. However, the methods of intubation and success rates were highly variable among hospitals. 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.

Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial.

PubMed

Chupp, Geoffrey L; Bradford, Eric S; Albers, Frank C; Bratton, Daniel J; Wang-Jairaj, Jie; Nelsen, Linda M; Trevor, Jennifer L; Magnan, Antoine; Ten Brinke, Anneke

2017-05-01

Mepolizumab, an anti-interleukin-5 monoclonal antibody approved as add-on therapy to standard of care for patients with severe eosinophilic asthma, has been shown in previous studies to reduce exacerbations and dependency on oral corticosteroids compared with placebo. We aimed to further assess mepolizumab in patients with severe eosinophilic asthma by examining its effect on health-related quality of life (HRQOL). We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial (MUSCA) in 146 hospitals or research centres in 19 countries worldwide. Eligible participants were patients aged 12 years or older with severe eosinophilic asthma and a history of at least two exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids plus other controller medicines. Exclusion criteria included current smokers or former smokers with a history of at least ten pack-years. We randomly assigned participants (1:1) by country to receive a subcutaneous injection of either mepolizumab 100 mg or placebo, plus standard of care, every 4 weeks for 24 weeks (the final dose was given at week 20). We did the randomisation using an interactive voice response system and a centralised, computer-generated, permuted-block design of block size six. The two treatments were identical in appearance and administered in a masked manner; patients, investigators, other site staff and the entire study team including those assessing outcomes data were also masked to group assignment. The primary endpoint was the mean change from baseline in the St George's Respiratory Questionnaire (SGRQ) total score at week 24 in the modified intention-to-treat (modified ITT) population (analysed according to their randomly assigned treatment). Safety was assessed in all patients who received at least one dose of trial medication (analysed according to the actual treatment received). This trial is registered with ClinicalTrials.gov, number NCT02281318. We recruited patients between Dec 11, 2014, and Nov 20, 2015, and the study was undertaken between Dec 11, 2014, and June 10, 2016. The modified ITT population comprised 274 patients assigned to mepolizumab 100 mg and 277 assigned to placebo. Mepolizumab versus placebo showed significant improvements at week 24 from baseline in SGRQ total score (least squares mean [SE] change from baseline -15·6 (1·0) vs -7·9 (1·0), a treatment difference of -7·7 (95% CI -10·5 to -4·9; p<0·0001). No deaths occurred during the study. 192 (70%) of 273 patients who received mepolizumab and 207 (74%) of 278 who received placebo reported at least one on-treatment adverse event, the most common of which were headache (in 45 [16%] given mepolizumab vs 59 [21%] given placebo) and nasopharyngitis (in 31 [11%] given mepolizumab vs 46 [17%] given placebo). 15 (5%) and 22 (8%) patients had an on-treatment serious adverse event in the mepolizumab and placebo groups, respectively; the most common was asthma in both groups (in three [1%] given mepolizumab vs nine [3%] given placebo). Mepolizumab was associated with significant improvements in HRQOL in patients with severe eosinophilic asthma, and had a safety profile similar to that of placebo. These results add to and support the use of mepolizumab as a favourable add-on treatment option to standard of care in patients with severe eosinophilic asthma. GlaxoSmithKline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

PubMed

Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

The new system of review by multicentre research ethics committees: prospective study

PubMed Central

Tully, Joanna; Ninis, Nelly; Booy, Robert; Viner, Russell

2000-01-01

Objective To assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed. Design Prospectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited. Setting A single multicentre research ethics committee and 125 local ethics committees from six regions of England. Main outcome measures Time to reply, time to approval, and number of non-local changes to the application requested. Results Only 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested. Conclusions The new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims. PMID:10784541

Impact of rapid antigen detection testing on antibiotic prescription in acute pharyngitis in adults. FARINGOCAT STUDY: a multicentric randomized controlled trial

PubMed Central

2010-01-01

Background Acute pharyngitis is one of the most frequent consultations to the general practitioner and in most of the cases an antibiotic is prescribed in primary care in Spain. Bacterial etiology, mainly by group A beta-hemolytic streptococcus (GABHS), accounts for 10-20% of all these infections in adults. The purpose of this study is to assess the impact of rapid antigen detection testing (RADT) to identify GABHS in acute pharyngitis on the utilization of antibiotics in primary care. Methods/design Multicentric randomized controlled trial in which antibiotic prescription between two groups of patients with acute pharyngitis will be compared. The trial will include two arms, a control and an intervention group in which RADT will be performed. The primary outcome measure will be the proportion of inappropriate antibiotic prescription in each group. Two hundred seventy-six patients are required to detect a reduction in antibiotic prescription from 85% in the control group to 75% in the intervention group with a power of 90% and a level of significance of 5%. Secondary outcome measures will be specific antibiotic treatment, antibiotic resistance rates, secondary effects, days without working, medical visits during the first month and patient satisfaction. Discussion The implementation of RADT would allow a more rational use of antibiotics and would prevent adverse effects of antibiotics, emergence of antibiotic resistance and the growth of inefficient health expenses. Trial registration ISRCTN23587778 PMID:20331895

Rationale and design of the SERVE-HF study: treatment of sleep-disordered breathing with predominant central sleep apnoea with adaptive servo-ventilation in patients with chronic heart failure.

PubMed

Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita; Somers, Virend K; Zannad, Faiez; Teschler, Helmut

2013-08-01

Central sleep apnoea/Cheyne-Stokes respiration (CSA/CSR) is a risk factor for increased mortality and morbidity in heart failure (HF). Adaptive servo-ventilation (ASV) is a non-invasive ventilation modality for the treatment of CSA/CSR in patients with HF. SERVE-HF is a multinational, multicentre, randomized, parallel trial designed to assess the effects of addition of ASV (PaceWave, AutoSet CS; ResMed) to optimal medical management compared with medical management alone (control group) in patients with symptomatic chronic HF, LVEF ≤45%, and predominant CSA. The trial is based on an event-driven group sequential design, and the final analysis will be performed when 651 events have been observed or the study is terminated at one of the two interim analyses. The aim is to randomize ∼1200 patients to be followed for a minimum of 2 years. Patients are to stay in the trial up to study termination. The first patient was randomized in February 2008 and the study is expected to end mid 2015. The primary combined endpoint is the time to first event of all-cause death, unplanned hospitalization (or unplanned prolongation of a planned hospitalization) for worsening (chronic) HF, cardiac transplantation, resuscitation of sudden cardiac arrest, or appropriate life-saving shock for ventricular fibrillation or fast ventricular tachycardia in implantable cardioverter defibrillator patients. The SERVE-HF study is a randomized study that will provide important data on the effect of treatment with ASV on morbidity and mortality, as well as the cost-effectiveness of this therapy, in patients with chronic HF and predominantly CSA/CSR. ISRCTN19572887.

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

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.

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.

Reporting of participant flow diagrams in published reports of randomized trials.

PubMed

Hopewell, Sally; Hirst, Allison; Collins, Gary S; Mallett, Sue; Yu, Ly-Mee; Altman, Douglas G

2011-12-05

Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented.

Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial.

PubMed

Winter, Michiel M; van der Bom, Teun; de Vries, Leonie C S; Balducci, Anna; Bouma, Berto J; Pieper, Petronella G; van Dijk, Arie P J; van der Plas, Mart N; Picchio, Fernando M; Mulder, Barbara J M

2012-06-01

To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. Multi-centre parallel randomized controlled trial. Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. Forty-six patients were analysed (male 50%, age 32 ± 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( The study was registered at http://trialregister.nl. Identifier: NTR1909.).

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

Staff regard towards working with substance users: a European multi-centre study.

PubMed

Gilchrist, Gail; Moskalewicz, Jacek; Slezakova, Silvia; Okruhlica, Lubomir; Torrens, Marta; Vajd, Rajko; Baldacchino, Alex

2011-06-01

To compare regard for working with different patient groups (including substance users) among different professional groups in different health-care settings in eight European countries. A multi-centre, cross-sectional comparative study. Primary care, general psychiatry and specialist addiction services in Bulgaria, Greece, Italy, Poland, Scotland, Slovakia, Slovenia and Spain. A multi-disciplinary convenience sample of 866 professionals (physicians, psychiatrists, psychologists, nurses and social workers) from 253 services. The Medical Condition Regard Scale measured regard for working with different patient groups. Multi-factor between-subjects analysis of variance determined the factors associated with regard for each condition by country and all countries. Regard for working with alcohol (mean score alcohol: 45.35, 95% CI 44.76, 45.95) and drug users (mean score drugs: 43.67, 95% CI 42.98, 44.36) was consistently lower than for other patient groups (mean score diabetes: 50.19, 95% CI 49.71, 50.66; mean score depression: 51.34, 95% CI 50.89, 51.79) across all countries participating in the study, particularly among staff from primary care compared to general psychiatry or specialist addiction services (P<0.001). After controlling for sex of staff, profession and duration of time working in profession, treatment entry point and country remained the only statistically significant variables associated with regard for working with alcohol and drug users. Health professionals appear to ascribe lower status to working with substance users than helping other patient groups, particularly in primary care; the effect is larger in some countries than others. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Assessing treatment-as-usual provided to control groups in adherence trials: Exploring the use of an open-ended questionnaire for identifying behaviour change techniques.

PubMed

Oberjé, Edwin J M; Dima, Alexandra L; Pijnappel, Frank J; Prins, Jan M; de Bruin, Marijn

2015-01-01

Reporting guidelines call for descriptions of control group support in equal detail as for interventions. However, how to assess the active content (behaviour change techniques (BCTs)) of treatment-as-usual (TAU) delivered to control groups in trials remains unclear. The objective of this study is to pre-test a method of assessing TAU in a multicentre cost-effectiveness trial of an HIV-treatment adherence intervention. HIV-nurses (N = 21) completed a semi-structured open-ended questionnaire enquiring about TAU adherence counselling. Two coders independently coded BCTs. Completeness and clarity of nurse responses, inter-coder reliabilities and the type of BCTs reported were examined. The clarity and completeness of nurse responses were adequate. Twenty-three of the 26 identified BCTs could be reliably coded (mean κ = .79; mean agreement rate = 96%) and three BCTs scored below κ = .60. Total number of BCTs reported per nurse ranged between 7 and 19 (M = 13.86, SD = 3.35). This study suggests that the TAU open-ended questionnaire is a feasible and reliable tool to capture active content of support provided to control participants in a multicentre adherence intervention trial. Considerable variability in the number of BCTs provided to control patients was observed, illustrating the importance of reliably collecting and accurately reporting control group support.

[Multicentre randomized trial comparing triptorelin medical castration versus surgical castration in the treatment of locally advanced or metastatic prostate cancer].

PubMed

Botto, Henry; Rouprêt, Morgan; Mathieu, François; Richard, François

2007-04-01

To report the results of a trial comparing the efficacy of triptorelin and surgical castration in the treatment of locally advanced or metastatic prostate cancer. 80 patients with previously untreated locally advanced or metastatic prostate cancer prostate cancer were included in a one-year multicentre, randomized, prospective, open-label therapeutic trial. Patients either received a monthly injection of triptorelin (group 1; n = 40), or were treated by pulpectomy (group 2; n = 40). Patients were reviewed every 3 months, then every 6 months. The mean age of the patients was 71.22 +/- 8.25 years. At 1 month, 38 patients were castrated (plasma testosterone < 0.5 mg/ml) in the pulpectomy group versus 35 in the triptorelin group. The mean follow-up was 38.8 +/- 26 months in the triptorelin group and 36.3 +/- 25 months in the pulpectomy group. On multivariate analysis, age, impaired performance status and PAP level (> 3.2 ng/ml) were predictive factors of a poor outcome. The median survival was 37.5 +/- 9 months in the triptorelin group and 33 +/- 3 months in the pulpectomy group. At 3 years, no significant difference in specific survival was observed between the 2 groups. At 8 years of follow-up, 63 patients had died. This study demonstrates an equivalent specific survival between patients treated by triptorelin or surgical castration. Castration is rapidly obtained with triptorelin (< 2 months) and is maintained over time throughout the duration of treatment.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study

PubMed Central

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-01-01

Background Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). Methods In-depth semi-structured telephone interviews were conducted in 2003–04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. Results The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. Conclusion This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research. PMID:17184521

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years.

PubMed

Willett, Keith; Keene, David J; Morgan, Lesley; Gray, Bridget; Handley, Robert; Chesser, Tim; Pallister, Ian; Tutton, Elizabeth; Knox, Christopher; Lall, Ranjit; Briggs, Andrew; Lamb, Sarah E

2014-03-12

Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Current Controlled Trials ISRCTN04180738.

Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial

PubMed Central

Skinner, Elizabeth H; Browning, Laura; Reeve, Julie; Anderson, Lesley; Hill, Cat; Robertson, Iain K; Story, David; Denehy, Linda

2018-01-01

Abstract Objective To assess the efficacy of a single preoperative physiotherapy session to reduce postoperative pulmonary complications (PPCs) after upper abdominal surgery. Design Prospective, pragmatic, multicentre, patient and assessor blinded, parallel group, randomised placebo controlled superiority trial. Setting Multidisciplinary preadmission clinics at three tertiary public hospitals in Australia and New Zealand. Participants 441 adults aged 18 years or older who were within six weeks of elective major open upper abdominal surgery were randomly assigned through concealed allocation to receive either an information booklet (n=219; control) or preoperative physiotherapy (n=222; intervention) and followed for 12 months. 432 completed the trial. Interventions Preoperatively, participants received an information booklet (control) or an additional 30 minute physiotherapy education and breathing exercise training session (intervention). Education focused on PPCs and their prevention through early ambulation and self directed breathing exercises to be initiated immediately on regaining consciousness after surgery. Postoperatively, all participants received standardised early ambulation, and no additional respiratory physiotherapy was provided. Main outcome measures The primary outcome was a PPC within 14 postoperative hospital days assessed daily using the Melbourne group score. Secondary outcomes were hospital acquired pneumonia, length of hospital stay, utilisation of intensive care unit services, and hospital costs. Patient reported health related quality of life, physical function, and post-discharge complications were measured at six weeks, and all cause mortality was measured to 12 months. Results The incidence of PPCs within 14 postoperative hospital days, including hospital acquired pneumonia, was halved (adjusted hazard ratio 0.48, 95% confidence interval 0.30 to 0.75, P=0.001) in the intervention group compared with the control group, with an absolute risk reduction of 15% (95% confidence interval 7% to 22%) and a number needed to treat of 7 (95% confidence interval 5 to 14). No significant differences in other secondary outcomes were detected. Conclusion In a general population of patients listed for elective upper abdominal surgery, a 30 minute preoperative physiotherapy session provided within existing hospital multidisciplinary preadmission clinics halves the incidence of PPCs and specifically hospital acquired pneumonia. Further research is required to investigate benefits to mortality and length of stay. Trial registration Australian New Zealand Clinical Trials Registry ANZCTR 12613000664741. PMID:29367198

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

Acceptability of the female condom in different groups of women in South Africa--a multicentred study to inform the national female condom introductory strategy.

PubMed

Beksinska, M E; Rees, V H; McIntyre, J A; Wilkinson, D

2001-08-01

To assess the acceptability of the female condom to different groups of women and their partners in South Africa. Descriptive, cross-sectional study. Multicentre study conducted in five sites. The study recruited 678 women from five centres to an acceptability trial of the female condom. Acceptability and successful use varied between the centres. Factors affecting successful use and willingness and intention to use the method again. In total, 209 women used the condom at least once. Discontinuation rates were high, with partner reluctance to try the method as the main reason given for discontinuation at all sites. Women who had previous experience with the male condom or who received a more intensive training session generally found the device easier to use. The main issues concerning women were over-lubrication (27%) and concern that the device was too large (28%). The majority of women said that they would be interested in using the method again (86%) and would recommend it to friends (95%). Overcoming partner opposition is an important issue to address when introducing the method. The study was used to address the national introductory strategy of the female condom, which began in 1998.

Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma.

PubMed

Treggiari, E; Elliott, J W; Baines, S J; Blackwood, L

2018-06-01

Temozolomide (TMZ) is an alkylating agent previously used in conjunction with doxorubicin (DOX) to treat dogs with relapsed lymphoma. However, there are very limited data for this drug when used as single agent. The aim of this retrospective study was to evaluate the efficacy and toxicity of TMZ in dogs with relapsed multicentric lymphoma that failed multi-agent chemotherapy protocols, and compare the outcome to a group of dogs receiving the same drug in combination with DOX. Twenty-six patients were included in the TMZ group and 11 in the TMZ/DOX group. Responses were evaluated via retrospective review of the medical records. The overall median survival time (MST) for both groups was 40 days (range 1-527 days). For the TMZ group, median time to progression (TTP) was 15 days (range 1-202 days) and MST 40 days (range 1-527 days), with an overall response rate (ORR) of 32% and 46% recorded toxicities. For the TMZ/DOX group, median TTP was 19 days (range 2-87 days) and MST 24 days (range 3-91 days), with an ORR of 60% and 63% recorded toxicities. However, a proportion of haematological toxicoses may have gone undetected due to the absence of associated clinical signs. The difference in MST and TTP between the 2 groups was not statistically significant. Similarly, no negative prognostic factors were identified. Although responses were generally short lived, this study suggests that TMZ may achieve similar efficacy to TMZ/DOX whilst being associated with a lower frequency of recorded toxicities. © 2017 John Wiley & Sons Ltd.

Impact of tailored patient education on adherence of patients with chronic myeloid leukaemia to tyrosine kinase inhibitors: a randomized multicentre intervention study.

PubMed

Kekäle, Meri; Söderlund, Tim; Koskenvesa, Perttu; Talvensaari, Kimmo; Airaksinen, Marja

2016-09-01

The aim of this study was to evaluate the influence of tailored patient education on adherence to tyrosine kinase inhibitor medication among patients with chronic myeloid leukaemia. Management of chronic myeloid leukaemia has changed dramatically during the last decade. While medication adherence is crucial to clinical response, little is known about how to improve patients' adherence. Randomized multicentre intervention study. The study was conducted between June 2012-August 2014. Eighty-six patients with chronic myeloid leukaemia who had been on tyrosine kinase inhibitor medication for at least six months from eight hospitals were randomized into intervention and control groups. Intervention combined nurse-conducted medication counselling, an information booklet, video and website and text message reminders. Patients were interviewed to assess medication adherence using Morisky's 8-Item Medication Adherence Scale at baseline and nine months. Medication adherence improved with the adherence aids used. At nine months, 51% of patients were highly adherent in the intervention group, compared with 21% in the control group. Adherence improved for a higher proportion of patients in the intervention group than the control group (49% vs. 18%). Morisky's score decreased in almost half of control group cases. Patients were most satisfied with face-to-face counselling (86%) and the information booklet (83%) and least satisfied with text messages (9%). Tailored patient education improved the medication adherence of patients with chronic myeloid leukaemia. Without this, adherence behaviour tended to decline. Personal communication with a nurse proved to be an essential part of adherence support and should not be ignored. © 2016 John Wiley & Sons Ltd.

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial

PubMed Central

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-01-01

Introduction The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. Methods and analysis We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. Ethics and dissemination This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016–0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. Trial registration number The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. PMID:28801436

Work productivity and activity impairment in gastroesophageal reflux disease in Korean full-time employees: a multicentre study.

PubMed

Shin, Woon Geon; Kim, Heung Up; Kim, Sang Gyun; Kim, Gwang Ha; Shim, Ki-Nam; Kim, Jeong Wook; Kim, Jin Il; Kim, Jae Gyu; Kim, Jae J; Yim, Da-Hae; Park, Sue K; Park, Soo-Heon

2012-04-01

The costs of gastroesophageal reflux disease have not been assessed in Asia, even though the prevalence of gastroesophageal reflux disease is gradually increasing. We evaluated work presenteeism and absenteeism as indirect costs of gastroesophageal reflux disease in Korea. This was a cross-sectional and multicentre study using patient-reported outcome instruments. A total of 1009 full-time employees who visited the gastrointestinal department for any reason (281 patients with gastroesophageal reflux disease and 728 controls) were included. Main outcomes were presenteeism and absenteeism measured as work productivity loss and monetary cost per week. Absenteeism and presenteeism were significantly higher in the gastroesophageal reflux disease than the control group (1.49% vs. 0.46%, P=0.0010; 34.13% vs. 9.23%, P<0.0001). Loss of work productivity was significantly greater in the gastroesophageal reflux disease than the control group (33.09% vs. 9.02%; P<0.0001). This loss of work productivity difference between the two groups represented an additional productivity loss of 11.7h/week in the gastroesophageal reflux disease group compared with the control group. Assuming average hourly wages of $14.12, the weekly burden of gastroesophageal reflux disease reached $165.07 per person. Gastroesophageal reflux disease was associated with substantial work productivity loss, mainly due to presenteeism rather than absenteeism, in Korean full-time employees. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Twice-daily and three-times-daily dosing of a repaglinide/metformin fixed-dose combination tablet provide similar glycaemic control.

PubMed

Raskin, P; Lewin, A; Reinhardt, R; Lyness, W

2009-10-01

To assess the efficacy and safety of a new repaglinide/metformin fixed-dose combination (FDC) tablet administered either twice a day (BID) or three times a day (TID) for the management of type 2 diabetes. This was a 26-week, multicentre, open-label parallel trial in which subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to instead receive repaglinide/metformin FDC either BID or TID or a rosiglitazone/metformin FDC BID. Two primary hypotheses were tested in a hierarchical manner: (i) treatment with the repaglinide/metformin FDC BID is non-inferior to that of the rosiglitazone/metformin FDC BID as measured by changes in haemoglobin A1c (HbA1c) (results presented in companion paper) and (ii) repaglinide/metformin BID is non-inferior to repaglinide/metformin TID (as measured by changes in HbA1c). Additional efficacy and safety end-points were also assessed. A total of 561 subjects were randomized; 383 completed the study. Repaglinide/metformin FDC BID was non-inferior to repaglinide/metformin FDC TID with respect to HbA1c. Additionally, changes in mean fasting plasma glucose values from baseline to end of study were not significantly different between the BID and the TID dose groups. There were no major hypoglycaemic episodes reported in either group during the trial, and overall adverse event profiles were similar. The efficacy of twice-daily dosing of a repaglinide/metformin FDC tablet was non-inferior to that of three-times-daily dosing.

Does the use of Nintendo Wii SportsTM improve arm function? Trial of WiiTM in Stroke: a randomized controlled trial and economics analysis.

PubMed

Adie, Katja; Schofield, Christine; Berrow, Margie; Wingham, Jennifer; Humfryes, John; Pritchard, Colin; James, Martin; Allison, Rhoda

2017-02-01

The Trial of Wii™ in Stroke investigated the efficacy of using the Nintendo Wii Sports™ (Wii TM ) to improve affected arm function after stroke. Multicentre, pragmatic, parallel group, randomized controlled trial. Home-based rehabilitation. A total of 240 participants aged 24-90 years with arm weakness following a stroke within the previous six months. Participants were randomly assigned to exercise daily for six weeks using the Wii TM or arm exercises at home. Primary outcome was change in the affected arm function at six weeks follow-up using the Action Research Arm Test. Secondary outcomes included occupational performance, quality of life, arm function at six months and a cost effectiveness analysis. The study was completed by 209 participants (87.1%). There was no significant difference in the primary outcome of affected arm function at six weeks follow-up (mean difference -1.7, 95% CI -3.9 to 0.5, p = 0.12) and no significant difference in secondary outcomes, including occupational performance, quality of life or arm function at six months, between the two groups. No serious adverse events related to the study treatment were reported. The cost effectiveness analysis showed that the Wii TM was more expensive than arm exercises £1106 (SD 1656) vs. £730 (SD 829) (probability 0.866). The trial showed that the Wii TM was not superior to arm exercises in home-based rehabilitation for stroke survivors with arm weakness. The Wii TM was well tolerated but more expensive than arm exercises.

The CLIMB (Complex Lipids In Mothers and Babies) study: protocol for a multicentre, three-group, parallel randomised controlled trial to investigate the effect of supplementation of complex lipids in pregnancy, on maternal ganglioside status and subsequent cognitive outcomes in the offspring.

PubMed

Huang, Shuai; Mo, Ting-Ting; Norris, Tom; Sun, Si; Zhang, Ting; Han, Ting-Li; Rowan, Angela; Xia, Yin-Yin; Zhang, Hua; Qi, Hong-Bo; Baker, Philip N

2017-10-12

Complex lipids are important constituents of the central nervous system. Studies have shown that supplementation with complex milk lipids (CML) in pregnancy may increase the level of fetal gangliosides (GA), with the potential to improve cognitive outcomes. We aim to recruit approximately 1500 pregnant women in the first trimester (11-14 weeks) and randomise them into one of the three treatment groups: standard maternal milk formulation, CML-enhanced maternal milk formulation or no maternal milk intervention with standard pregnancy advice (ie, the standard care). Maternal lifestyle and demographic data will be collected throughout the pregnancy, as well as biological samples (eg, blood, hair, urine, buccal smear, cord blood, cord and placenta samples). Data from standard obstetric care recorded in hospital maternity notes (eg, ultrasound reports, results of oral glucose tolerance test and pregnancy outcome data) will also be extracted. Postnatal follow-up will be at 6 weeks and 12 months of age, at which point infant cognitive development will be assessed (Bayley Scales of Infant Development I). This project was approved by the Ethics Committee of Chongqing Medical University. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences. ChiCTR-IOR-16007700; 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.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials.

PubMed

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials.

Effects of Gyejibongnyeong-hwan on dysmenorrhea caused by blood stagnation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Gyejibongnyeong-hwan (GJBNH) is one of the most popular Korean medicine formulas for menstrual pain of dysmenorrhea. The concept of blood stagnation in Korean medicine is considered the main factor of causing abdominal pain, or cramps, during menstrual periods. To treat the symptoms, GJBNH is used to fluidify the stagnated blood and induce the blood flow to be smooth, reducing pain as the result. The purpose of this trial is to identify the efficacy of GJBNH in dysmenorrhea caused by blood stagnation. Methods This study is a multi-centre, randomised, double-blind, controlled trial with two parallel arms: the group taking GJBNH and the group taking placebo. 100 patients (women from age 18 to 35) will be enrolled to the trial. Through randomization 50 patients will be in experiment arm, and the other 50 patients will be in control arm. At the second visit (baseline), all participants who were already screened that they fulfil both the inclusion and the exclusion criteria will be randomised into two groups. Each group will take the intervention three times per day during two menstrual cycles. After the treatment for two cycles, each patient will be followed up during their 3rd, 4th and 5th menstrual cycles. From the screening (Visit 1) through the second follow-up (Visit 6) the entire process will take 25 weeks. Discussion This trial will provide evidence for the effectiveness of GJBNH in treating periodical pain due to dysmenorrhea that is caused by blood stagnation. The primary outcome between the two groups will be measured by changes in the Visual Analogue Score (VAS) of pain. The secondary outcome will be measured by the Blood Stagnation Scale, the Short-form McGill questionnaire and the COX menstrual symptom scale. Analysis of covariance (ANCOVA) and repeated measured ANOVA will be used to analyze the data analysis. Trial registration Current Controlled Trials: ISRCTN30426947 PMID:22217258

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The impact of long-term growth hormone treatment on metabolic parameters in Japanese patients with short stature born small for gestational age.

PubMed

Kappelgaard, Anne-Marie; Kiyomi, Fumiaki; Horikawa, Reiko; Yokoya, Susumu; Tanaka, Toshiaki

2014-01-01

An examination of the effects of up to 260 weeks of growth hormone (GH) therapy on metabolic parameters in Japanese children born small for gestational age (SGA). Data were analysed from a 156-week extension of a 104-week multicentre, randomised, double-blind, parallel-group trial. Sixty-five children born SGA (age 3-<8 years) received 33 μg/kg/day (n = 31, 64.5% male) or 67 μg/kg/day (n = 34, 58.8% male) GH for 260 weeks. Changes in metabolic parameters - glucose, insulin, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol - were recorded. Alterations in weight, body mass index standard deviation score (BMI SDS) and vital signs were also evaluated. Over 260 weeks of GH treatment, a positive correlation between Δheight SDS and Δinsulin-like growth factor-I SDS was observed. Insulin and glucose levels were generally unaffected. Favourable changes in lipid profiles were recorded, which were maintained for the study duration. No adverse alterations in weight, BMI SDS or vital signs were noted. Long-term, continuous GH treatment in children born SGA appears to be efficacious, associated with potential benefits for several metabolic parameters and associated with no long-term safety concerns.

[Double-blind randomized comparative study of nicergoline naftidrofuryl on the quality of life in chronic obliterative arteriopathy of lower limbs with intermittent claudication].

PubMed

Meilhac, B; Montestruc, F; Aubin, F; Djian, F; Rouffy, J

1997-01-01

The functional limitation of patients with obliterative arterial disease, and with intermittent claudication, damages their quality of life. The purpose of this trial was to compare the effects of nicergoline and naftidrofuryl on the quality of life and the functional discomfort of the 131 patients with claudication. It was a multicentre, randomised, double-blind trial with parallel groups. The patients were asked to complete a quality of life questionnaire and a Visual Analogue Scale, and to evaluate the number of steps on flat ground before the pain began. After 6 months of treatment, we observed, for all treatments combined, a significant improvement (p = 0.0001) in the quality of life and in the functional discomfort. Three variables favoured nicergoline: the estimated time before the onset of the pain (p = 0.003), the functional discomfort quantified by the Visual Analogue Scale (p < 0.05), the distance covered on flat ground (p = 0.013). The other variables, and especially the total score on the self-questionnaire, confirmed this impression, without reaching significance (p = 0.136). The data suggest that in terms of quality of life nicergoline is superior. The clinical tolerance is good and comparable between the two treatments.

Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial.

PubMed

Bath-Hextall, Fiona; Ozolins, Mara; Armstrong, Sarah J; Colver, Graham B; Perkins, William; Miller, Paul S J; Williams, Hywel C

2014-01-01

Basal-cell carcinoma is the most common form of skin cancer and its incidence is increasing worldwide. We aimed to assess the effectiveness of imiquimod cream versus surgical excision in patients with low-risk basal-cell carcinoma. We did a multicentre, parallel-group, pragmatic, non-inferiority, randomised controlled trial at 12 centres in the UK, in which patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year follow-up from June 26, 2006, to May 26, 2010. Participants of any age were eligible if they had histologically confirmed primary nodular or superficial basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were randomly assigned (1:1) via computer-generated blocked randomisation, stratified by centre and tumour type, to receive either imiquimod 5% cream once daily for 6 weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm margin. The randomisation sequence was concealed from study investigators. Because of the nature of the interventions, masking of participants was not possible and masking of outcome assessors was only partly possible. The trial statistician was masked to allocation until all analyses had been done. The primary outcome was the proportion of participants with clinical success, defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment. We used a prespecified non-inferiority margin of a relative risk (RR) of 0.87. Analysis was by a modified intention-to-treat population and per protocol. This study is registered as an International Standard Randomised Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number NCT00066872. 501 participants were randomly assigned to the imiquimod group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%) patients were included in the modified intention-to-treat group. At 3 years, 178 (84%) of 213 participants in the imiquimod group were treated successfully compared with 185 (98%) of 188 participants in the surgery group (RR 0.84, 98% CI 0.78-0.91; p<0.0001). No clear difference was noted between groups in patient-assessed cosmetic outcomes. The most common adverse events were itching (211 patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs 81). We recorded serious adverse events in 99 (40%) of 249 participants in the imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse events, but none were regarded as related to treatment. 12 (5%) participants in the imiquimod group withdrew because of adverse events compared with four (2%) in the surgery group. Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion. Cancer Research UK. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

PubMed

Henriksen, Hege Berg; Ræder, Hanna; Bøhn, Siv Kjølsrud; Paur, Ingvild; Kværner, Ane Sørlie; Billington, Siv Åshild; Eriksen, Morten Tandberg; Wiedsvang, Gro; Erlund, Iris; Færden, Arne; Veierød, Marit Bragelien; Zucknick, Manuela; Smeland, Sigbjørn; Blomhoff, Rune

2017-01-30

Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population. ClinicalTrials.gov Identifier: NCT01570010 .

Balance exercise for persons with multiple sclerosis using Wii games: a randomised, controlled multi-centre study.

PubMed

Nilsagård, Ylva E; Forsberg, Anette S; von Koch, Lena

2013-02-01

The use of interactive video games is expanding within rehabilitation. The evidence base is, however, limited. Our aim was to evaluate the effects of a Nintendo Wii Fit® balance exercise programme on balance function and walking ability in people with multiple sclerosis (MS). A multi-centre, randomised, controlled single-blinded trial with random allocation to exercise or no exercise. The exercise group participated in a programme of 12 supervised 30-min sessions of balance exercises using Wii games, twice a week for 6-7 weeks. Primary outcome was the Timed Up and Go test (TUG). In total, 84 participants were enrolled; four were lost to follow-up. After the intervention, there were no statistically significant differences between groups but effect sizes for the TUG, TUGcognitive and, the Dynamic Gait Index (DGI) were moderate and small for all other measures. Statistically significant improvements within the exercise group were present for all measures (large to moderate effect sizes) except in walking speed and balance confidence. The non-exercise group showed statistically significant improvements for the Four Square Step Test and the DGI. In comparison with no intervention, a programme of supervised balance exercise using Nintendo Wii Fit® did not render statistically significant differences, but presented moderate effect sizes for several measures of balance performance.

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial.

PubMed

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-12-11

Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Randomised multicentre clinical trial. Post hoc analyses of the DASH-Sodium trial in the USA. In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. NCT00000608. 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.

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

PubMed

Jang, J-H; Jung, Y M; Kim, J S; Lee, S H; Kim, J-W; Hwang, S G; Rim, K S; Park, S J; Park, Y M; Kang, S-K; Lee, H S; Yun, H; Kim, J-H; Jeong, S-H

2011-10-01

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution. © 2011 Blackwell Publishing Ltd.

Effect of vaginal spheres and pelvic floor muscle training in women with urinary incontinence: a randomized, controlled trial.

PubMed

Porta-Roda, Oriol; Vara-Paniagua, Jesús; Díaz-López, Miguel A; Sobrado-Lozano, Pilar; Simó-González, Marta; Díaz-Bellido, Paloma; Reula-Blasco, María C; Muñoz-Garrido, Francisco

2015-08-01

To compare the efficacy and safety of Kegel exercises performed with or without, vaginal spheres as treatment for women with urinary incontinence. Multicentre parallel-group, open, randomized controlled trial. Women were allocated to either a pelvic floor muscle-training program consisting of Kegel exercises performed twice daily, 5 days/week at home, over 6 months with vaginal spheres, or to the same program without spheres. The primary endpoint was women's report of urinary incontinence at 6 months using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF). Secondary outcome measures were the 1 hr pad-test, King's Health Questionnaire (KHQ) and a five-point Likert scale for subjective evaluation. Adherence was measured with the Morisky-Green test. Thirty-seven women were randomized to the spheres group and 33 to the control group. The primary endpoint was evaluated in 65 women (35 in the spheres group vs. 30 controls). ICIQ-UI-SF results improved significantly at 1-month follow-up in the spheres group (P < 0.01) and at 6 months in the controls. The 1 hr pad-test improved in the spheres group but not in the control group. No significant differences were found in the KHQ results or in the subjective evaluation of efficacy and safety. Adherence was higher in the spheres group but differences were not significant. Mild transient side effects were reported in four patients in the spheres group and one in the control group. Both treatments improved urinary incontinence but women who performed the exercises with vaginal spheres showed an earlier improvement. Vaginal spheres were well tolerated and safe. © 2014 Wiley Periodicals, Inc.

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.

Cut-off of anthropometry measurement and nutritional status among elderly outpatient in Indonesia: multi-centre study.

PubMed

Setiati, Siti; Istanti, Rahmi; Andayani, Rejeki; Kuswardhani, R A Tuty; Aryana, I G P Suka; Putu, I Dewa; Apandi, M; Ichwani, Jusri; Soewoto, Sumarmi; Dinda, Rose; Mustika, Syifa

2010-10-01

To obtain the cut-off value of anthropometric measurements and nutritional status of elderly in Indonesia. A multicentre-cross sectional study was performed at 9 hospitals in Indonesia. The data collected comprises of samples characteristics, anthropometric measurements (weight, height, trisep, bisep, subscapular, suprailiac, and circumference of the hip, waist, arm, calf, and thigh), albumin value, MNA score and ADL Index of Barthel. A total of 702 subjects were collected. The average value of serum albumin is 4.28 g/dl, with 98% subjects had normal serum albumin (> 3.5 g/dl). The mean MNA score and BMI was 23.07 and 22.54 respectively. Most of subjects (56.70%) had risk of malnutrition based on MNA score, and 45.01% had normal nutritional status based on body mass index. Average value of several anthropometric measures (weight, stature, and body mass index; sub-scapular and supra-iliac skinfolds; thigh, calf, mid-arm, and waist circumferences) in various age groups in both groups of women and men were obtained. Cut-off values of various anthropometric indicators were also analyzed in this study with MNA as a gold standard. This study showed age related anthropometric measurement differences in both men and women aged 60 years and older.

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 novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

PubMed

Ikeda, S; Takano, Y; Cynshi, O; Tanaka, R; Christ, A D; Boerlin, V; Beyer, U; Beck, A; Ciorciaro, C; Meyer, M; Kadowaki, T

2015-10-01

To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM. © 2015 John Wiley & Sons Ltd.

The HubBLe Trial: haemorrhoidal artery ligation (HAL) versus rubber band ligation (RBL) for symptomatic second- and third-degree haemorrhoids: a multicentre randomised controlled trial and health-economic evaluation.

PubMed

Brown, Steven; Tiernan, Jim; Biggs, Katie; Hind, Daniel; Shephard, Neil; Bradburn, Mike; Wailoo, Allan; Alshreef, Abualbishr; Swaby, Lizzie; Watson, Angus; Radley, Simon; Jones, Oliver; Skaife, Paul; Agarwal, Anil; Giordano, Pasquale; Lamah, Marc; Cartmell, Mark; Davies, Justin; Faiz, Omar; Nugent, Karen; Clarke, Andrew; MacDonald, Angus; Conaghan, Phillip; Ziprin, Paul; Makhija, Rohit

2016-11-01

Optimal surgical intervention for low-grade haemorrhoids is unknown. Rubber band ligation (RBL) is probably the most common intervention. Haemorrhoidal artery ligation (HAL) is a novel alternative that may be more efficacious. The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids. A multicentre, parallel-group randomised controlled trial. UK NHS and Personal Social Services. 17 NHS Trusts. Patients aged ≥ 18 years presenting with grade II/III (second- and third-degree) haemorrhoids, including those who have undergone previous RBL. HAL with Doppler probe compared with RBL. Primary outcome - recurrence at 1 year post procedure; secondary outcomes - recurrence at 6 weeks; haemorrhoid severity score; European Quality of Life-5 Dimensions, 5-level version (EQ-5D-5L); Vaizey incontinence score; pain assessment; complications; and cost-effectiveness. A total of 370 participants entered the trial. At 1 year post procedure, 30% of the HAL group had evidence of recurrence compared with 49% after RBL [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.42 to 3.51; p  = 0.0005]. The main reason for the difference was the number of extra procedures required to achieve improvement/cure. If a single HAL is compared with multiple RBLs then only 37.5% recurred in the RBL arm (adjusted OR 1.35, 95% CI 0.85 to 2.15; p  = 0.20). Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year (9% HAL and 29% RBL), suggesting significant deterioration in both groups over the year. Symptom score, EQ-5D-5L and Vaizey score improved in both groups compared with baseline, but there was no difference between interventions. Pain was less severe and of shorter duration in the RBL group; most of the HAL group who had pain had mild to moderate pain, resolving by 3 weeks. Complications were low frequency and not significantly different between groups. It appeared that HAL was not cost-effective compared with RBL. In the base-case analysis, the difference in mean total costs was £1027 higher for HAL. Quality-adjusted life-years (QALYs) were higher for HAL; however, the difference was very small (0.01) resulting in an incremental cost-effectiveness ratio of £104,427 per additional QALY. At 1 year, although HAL resulted in fewer recurrences, recurrence was similar to repeat RBL. Symptom scores, complications, EQ-5D-5L and continence score were no different, and patients had more pain in the early postoperative period after HAL. HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY. Blinding of participants and site staff was not possible. The incidence of recurrence may continue to increase with time. Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness. The polysymptomatic nature of haemorrhoidal disease requires a validated scoring system, and the data from this trial will allow further assessment of validity of such a system. These data add to the literature regarding treatment of grade II/III haemorrhoids. The results dovetail with results from the eTHoS study [Watson AJM, Hudson J, Wood J, Kilonzo M, Brown SR, McDonald A, et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial. Lancet 2016, in press.] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy. Combined results will allow expansion of analysis, allowing surgeons to tailor their treatment options to individual patients. Current Controlled Trials ISRCTN41394716. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 88. See the NIHR Journals Library website for further project information.

Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM).

PubMed

Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

2018-05-03

Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. The mean depression change was - 0.66 (95% confidence interval - 2.27 to 0.94) in the active group (n = 80) and - 3.30 (- 4.68 to -1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55-4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by - 1.11 (- 2.16 to - 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (- 0.11 to 6.19), p = 0.059] or pain [0.47 (- 0.77 to 1.71), p = 0.456] from 0 to 13 weeks. Thirty-five patients were withdrawn from the study because of adverse reactions, deterioration or death: 25 (31.3%) during active treatment [23 (52.3%) who received buprenorphine], and ten (12.2%) in the placebo group. The most frequently occurring adverse events were psychiatric (17 adverse reactions) and neurological (14 adverse reactions). Analgesic treatment did not reduce depression while placebo appeared to improve depressive symptoms significantly by comparison, possibly owing to the adverse effects of active buprenorphine. The risk of adverse events warrants caution when prescribing buprenorphine for people with advanced dementia. ClinicalTrials.gov NCT02267057 (registered 7 July, 2014) and Norwegian Medicines Agency EudraCT 2013-002226-23.

Development of a web-based register for the Dutch national study on biologicals in JIA: www.ABC-register.nl.

PubMed

Prince, F H M; Ferket, I S; Kamphuis, S; Armbrust, W; Ten Cate, R; Hoppenreijs, E P A H; Koopman-Keemink, Y; van Rossum, M A J; van Santen-Hoeufft, M; Twilt, M; van Suijlekom-Smit, L W A

2008-09-01

Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study. We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data. The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved. By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

Conducting a paediatric multi-centre RCT with an industry partner: challenges and lessons learned.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2012-11-01

There are many benefits of multi-centred research including large sample sizes, statistical power, timely recruitment and generalisability of results. However, there are numerous considerations when planning and implementing a multi-centred study. This article reviews the challenges and successes of planning and implementing a multi-centred prospective randomised control trial involving an industry partner. The research investigated the impact on psychosocial functioning of a cosmetic camouflage product for children and adolescents with burn scarring. Multi-centred studies commonly have many stakeholders. Within this study, six Australian and New Zealand paediatric burn units as well as an industry partner were involved. The inclusion of an industry partner added complexities as they brought different priorities and expectations to the research. Further, multifaceted ethical and institutional approval processes needed to be negotiated. The challenges, successes, lessons learned and recommendations from this study regarding Australian and New Zealand ethics and research governance approval processes, collaboration with industry partners and the management of differing expectations will be outlined. Recommendations for future multi-centred research with industry partners include provision of regular written reports for the industry partner; continual monitoring and prompt resolution of concerns; basic research practices education for industry partners; minimisation of industry partner contact with participants; clear roles and responsibilities of all stakeholders and utilisation of single ethical review if available. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

PubMed

Omitola, Olufemi Gbenga; Soyele, Olujide Oladele; Sigbeku, Opeyemi; Okoh, Dickson; Akinshipo, Abdulwarith Olaitan; Butali, Azeez; Adeola, Henry Ademola

2017-01-01

Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 th and 7 th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study)

PubMed Central

Birring, S S; Brew, J; Kilbourn, A; Edwards, V; Wilson, R; Morice, A H

2017-01-01

Objectives To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. Design A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. Setting 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. Participants Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0–100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). Interventions Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. Main outcome measures The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. Results At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was −5.9 mm (−14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was −4.2 mm (−12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference −11.6 mm (−20.6 to 2.7), p=0.01) and cough frequency (mean difference −8.1 mm (−16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs. Conclusions Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL. Trial registration number EudraCT number 2014-004255-31. PMID:28093442

Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.

PubMed

Reinisch, Walter; Panés, Julián; Khurana, Sunil; Toth, Gabor; Hua, Fei; Comer, Gail M; Hinz, Michelle; Page, Karen; O'Toole, Margot; Moorehead, Tara McDonnell; Zhu, Hua; Sun, YanHui; Cataldi, Fabio

2015-06-01

Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. ClinicalTrials.gov number NCT01284062. 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.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials

PubMed Central

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

Purpose This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. Methods The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. Results The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Conclusion Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials. PMID:27467882

Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British South Asians with hypertension

PubMed Central

Hobbs, FD Richard; Khan, Tahir; Collins, Barbara

2005-01-01

Background People from British South Asian communities have an increased risk of mortality from coronary heart disease (CHD). Doxazosin, a selective α1-adrenergic blocker, in addition to lowering blood pressure, has been shown to have positive effects on glucose metabolism and lipid profiles in patients with hypertension. Aim We studied doxazosin (1–8 mg) and bendrofluazide (2.5 mg) in patients of British South Asian origin with existing mild to moderate hypertension (doxazosin n = 78; bendrofluazide n = 82), to compare their effects on glucose and lipid metabolism in this group. Design of study A 34-week randomised, double-blind, parallel-group, multicentre study. Setting Primary care in the UK. Method All doxazosin patients started with an initial dose of 1 mg once daily, titrated to a maximum 8 mg once daily if diastolic blood pressure was >90 mmHg or was not <5 mmHg of the baseline value. The primary efficacy variables were mean glucose and total cholesterol concentrations at week 21. Result Doxazosin reduced glucose, total cholesterol, low-density lipoprotein-cholesterol and triglycerides and increased high-density lipoprotein-cholesterol. There were significant differences between doxazosin and bendrofluazide for glucose concentrations at week 21 (P = 0.029) and week 34 (P = 0.015), total cholesterol at week 21 (P = 0.048) and triglycerides at week 21 P = 0.047) and week 34 (P = 0.009). There was no significant difference in blood pressure lowering between the two treatments. Conclusion Doxazosin exhibits beneficial effects on glucose concentrations and lipid profile, in particular in lowering triglyceride concentrations in British South Asians. Whether these desirable characteristics translate to improved overall cardiovascular risk requires formal evaluation. PMID:15970067

A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.

PubMed

Gunatilake, Samal; Brims, Fraser J H; Fogg, Carole; Lawrie, Iain; Maskell, Nick; Forbes, Karen; Rahman, Najib; Morris, Steve; Ogollah, Reuben; Gerry, Stephen; Peake, Mick; Darlison, Liz; Chauhan, Anoop J

2014-09-19

Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.

Earlier triple therapy with pioglitazone in patients with type 2 diabetes.

PubMed

Charpentier, G; Halimi, S

2009-09-01

This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA(1c)) 6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA(1c) (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-B) were calculated. Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA(1c) and -2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA(1c) level of <8.5% achieved the HbA(1c) target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA(1c) level was >or= 8.5%, 13% achieved the HbA(1c) target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA(1c), FPG and surrogate measures of beta-cell function. Patients were more likely to reach target HbA(1c) levels (< 7.0%) with pioglitazone treatment if their baseline HbA(1c) levels were < 8.5%, highlighting the importance of early triple therapy.

Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

PubMed

Vickerstaff, Victoria; Ambler, Gareth; Bunce, Catey; Xing, Wen; Gazzard, Gus

2015-11-11

The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 .

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

PubMed

Shah, Gaurang R; Chaudhari, Manojkumar V; Patankar, Suresh B; Pensalwar, Shrikant V; Sabale, Vilas P; Sonawane, Navneet A

2012-09-15

Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator's global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study).

PubMed

Birring, S S; Brew, J; Kilbourn, A; Edwards, V; Wilson, R; Morice, A H

2017-01-16

To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0-100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was -5.9 mm (-14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was -4.2 mm (-12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference -11.6 mm (-20.6 to 2.7), p=0.01) and cough frequency (mean difference -8.1 mm (-16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs. Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL. EudraCT number 2014-004255-31. 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/.

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

Efficacy and safety of betahistine treatment in patients with Meniere’s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial)

PubMed Central

Adrion, Christine; Fischer, Carolin Simone; Wagner, Judith; Gürkov, Robert; Mansmann, Ulrich

2016-01-01

Study question What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere’s disease, compared with placebo? Methods The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere’s disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2×24 mg daily, (n=73)), or high dose betahistine (3×48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients’ diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Study answer and limitations Incidence of attacks related to Meniere’s disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of patients who did not receive any intervention to follow the natural course of the disease, the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms. What this study adds Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere’s disease, compared with placebo. The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere’s disease. Funding, competing interests, data sharing Support from the German Federal Ministry of Education and Research (BMBF support code 01KG0708). Potential competing interests have been reported in full at the end of the paper on thebmj.com. Data are available from the corresponding author (Michael.Strupp@med.uni-muenchen.de) or biostatistician (mansmann@ibe.med.uni-muenchen.de). Study registration EudraCT no 2005-000752-32; ISRCTN no ISRCTN44359668. PMID:26797774

Patients as teachers: a randomised controlled trial on the use of personal stories of harm to raise awareness of patient safety for doctors in training.

PubMed

Jha, Vikram; Buckley, Hannah; Gabe, Rhian; Kanaan, Mona; Lawton, Rebecca; Melville, Colin; Quinton, Naomi; Symons, Jools; Thompson, Zoe; Watt, Ian; Wright, John

2015-01-01

Patient safety training often provides learners with a health professional's perspective rather than the patient's. Personal narratives of health-related harm allow patients to share their stories with health professionals to influence clinical behaviour by rousing emotions and improving attitudes to safety. This study measured the impact of patient narratives used to train junior doctors in patient safety. An open, multi-centre, two-arm, parallel design randomised controlled trial was conducted in the North Yorkshire East Coast Foundation School (NYECFS). The intervention consisted of 1-h-long patient narratives followed by discussion. The control arm received conventional faculty-delivered teaching. The Attitude to Patient Safety Questionnaire (APSQ) and the Positive and Negative Affect Schedule (PANAS) were used to measure the impact of the intervention. 142 trainees received the intervention; 141 the control teaching. There was no evidence of a difference in post-intervention APSQ scores between the groups. There was a statistically significant difference in the underlying distribution of both post PA (positive affect) and post NA (negative affect) scores between the groups on the PANAS (p<0.001) with indications of both higher PA and NA scores in the intervention group. Involving patients with experiences of safety incidents in training has an ideological appeal and seems an obvious choice in designing safety interventions. On the basis of our primary outcome measure, we were unable to demonstrate effectiveness of the intervention in changing general attitudes to safety compared to control. While the intervention may impact on emotional engagement and learning about communication, we remain uncertain whether this will translate into improved behaviours in the clinical context or indeed if there are any negative effects. Grant reference no. RP-PG-0108-10049. 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.

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64.

PubMed

Miller, Julie M; Dewey, Marc; Vavere, Andrea L; Rochitte, Carlos E; Niinuma, Hiroyuki; Arbab-Zadeh, Armin; Paul, Narinder; Hoe, John; de Roos, Albert; Yoshioka, Kunihiro; Lemos, Pedro A; Bush, David E; Lardo, Albert C; Texter, John; Brinker, Jeffery; Cox, Christopher; Clouse, Melvin E; Lima, João A C

2009-04-01

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective "CORE-64" trial ("Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors"). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis.

PubMed

Ball, Susan; Vickery, Jane; Hobart, Jeremy; Wright, Dave; Green, Colin; Shearer, James; Nunn, Andrew; Cano, Mayam Gomez; MacManus, David; Miller, David; Mallik, Shahrukh; Zajicek, John

2015-02-01

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS. There were three objectives in the CUPID study: (1) to evaluate whether or not Δ(9)-THC could slow the course of progressive MS; (2) to assess the long-term safety of Δ(9)-THC; and (3) to explore newer ways of conducting clinical trials in progressive MS. The CUPID trial was a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were randomised in a 2 : 1 ratio to Δ(9)-THC or placebo. Randomisation was balanced according to Expanded Disability Status Scale (EDSS) score, study site and disease type. Analyses were by intention to treat, following a pre-specified statistical analysis plan. A cranial magnetic resonance imaging (MRI) substudy, Rasch measurement theory (RMT) analyses and an economic evaluation were undertaken. Twenty-seven UK sites. Adults aged 18-65 years with primary or secondary progressive MS, 1-year evidence of disease progression and baseline EDSS 4.0-6.5. Oral Δ(9)-THC (maximum 28 mg/day) or matching placebo. Three and 6 months, and then 6-monthly up to 36 or 42 months. Primary outcomes were time to EDSS progression, and change in Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) 20-point physical subscale (MSIS-29phys) score. Various secondary patient- and clinician-reported outcomes and MRI outcomes were assessed. RMT analyses examined performance of MS-specific rating scales as measurement instruments and tested for a symptomatic or disease-modifying treatment effect. Economic evaluation estimated mean incremental costs and quality-adjusted life-years (QALYs). Effectiveness - recruitment targets were achieved. Of the 498 randomised patients (332 to active and 166 to placebo), 493 (329 active and 164 placebo) were analysed. no significant treatment effect; hazard ratio EDSS score progression (active : placebo) 0.92 [95% confidence interval (CI) 0.68 to 1.23]; and estimated between-group difference in MSIS-29phys score (active-placebo) -0.9 points (95% CI -2.0 to 0.2 points). Secondary clinical and MRI outcomes: no significant treatment effects. Safety - at least one serious adverse event: 35% and 28% of active and placebo patients, respectively. RMT analyses - scale evaluation: MSIS-29 version 2, MS Walking Scale-12 version 2 and MS Spasticity Scale-88 were robust measurement instruments. There was no clear symptomatic or disease-modifying treatment effect. Economic evaluation - estimated mean incremental cost to NHS over usual care, over 3 years £27,443.20 per patient. No between-group difference in QALYs. The CUPID trial failed to demonstrate a significant treatment effect in primary or secondary outcomes. There were no major safety concerns, but unwanted side effects seemed to affect compliance. Participants were more disabled than in previous studies and deteriorated less than expected, possibly reducing our ability to detect treatment effects. RMT analyses supported performance of MS-specific rating scales as measures, enabled group- and individual person-level examination of treatment effects, but did not influence study inferences. The intervention had significant additional costs with no improvement in health outcomes; therefore, it was dominated by usual care and not cost-effective. Future work should focus on determining further factors to predict clinical deterioration, to inform the development of new studies, and modifying treatments in order to minimise side effects and improve study compliance. The absence of disease-modifying treatments in progressive MS warrants further studies of the cannabinoid pathway in potential neuroprotection. Current Controlled Trials ISRCTN62942668. The National Institute for Health Research Health Technology Assessment programme, the Medical Research Council Efficacy and Mechanism Evaluation programme, Multiple Sclerosis Society and Multiple Sclerosis Trust. The report will be published in full in Health Technology Assessment; Vol. 19, No. 12. See the NIHR Journals Library website for further project information.

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.

[Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized].

PubMed

Glinski, W; Chodynicka, B; Roszkiewicz, J; Bogdanowski, T; Lecewicz-Torun, B; Kaszuba, A; Bowszyc, J; Nowak, A; Wnorowski, J; Wasik, F; Glinska-Ferenz, M; Blaszczyk, M; Strzyga, P; Pachocki, R

2001-04-01

To determine the increase in healing rate of venous ulcer in patients receiving a micronised purified flavonoid fraction (MPFF) as supplementation to standard local care. A randomised, open, controlled, multicentre study. Departments of Dermatology and University Outpatients Clinics. One hundred and forty patients with chronic venous insufficiency and venous ulcers. PATIENTS received standard compressive therapy plus external treatment alone or 2 tablets of MPFF daily in addition to the above treatment for 24 weeks. Healing of ulcers and their reduction in size after 24 weeks of treatment. The percentage of patients whose ulcers healed completely was found to be markedly higher in those receiving MPFF in addition to standard external and compressive treatment than in those treated with conventional therapy alone (46.5% vs 27.5%; p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of patients in the MPFF group and in 50% of patients in the control group, whereas ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients (p<0.05), respectively. The mean reduction in ulcer size was also found to be greater in patients treated with MPFF (80%) than in the control group (65%) (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group was 1026.2 compared with 1871.8 in the control group. These results indicate that MPFF significantly improves the cure rate in patients with chronic venous insufficiency.

Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial.

PubMed

Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

2017-08-11

The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016-0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. The University Hospital Medical Information Network ID: UMIN000025727 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.

Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

PubMed

Santoro, Maria Mercedes; Di Carlo, Domenico; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

2017-09-22

Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. An observational multicentre retrospective study was performed. VS was defined as the first VL <50 copies/ml from treatment start. IR was defined as an increase of at least 150 CD4 + T-lymphocytes from treatment start. Survival analysis was used to estimate the probability and predictors of VS and IR by 12 months of therapy. 428 HIV-1-infected patients were analysed. Patients were grouped according to the different first-line drug-classes used: a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs; NNRTI-group; n=105 [24.5%]); a protease inhibitor (PI) plus two NRTIs (PI-group; n=260 [60.8%]); a four-drug regimen containing a PI-regimen plus an integrase inhibitor (PI+INI-group; n=63 [14.7%]). Patients in the PI-group showed the lowest probability of VS (PI-group: 72.4%; NNRTI-group: 75.5%; PI+INI-group: 81.0%; P<0.0001). By Cox regression, patients in PI+INI and NNRTI-groups showed a higher adjusted hazard ratio (95% CI) of VS compared to those in the PI-group (PI+INI-group: 1.48 [1.08, 2.03]; P=0.014; NNRTI-group: 1.37 [1.06-1.78]; P=0.015). The probability of IR was 76.2%, and was similar among groups. Patients with AIDS showed a lower adjusted hazard ratio (95% CI) of IR compared to non-AIDS presenters (0.70 [0.54, 0.90]; P=0.005). In this multicentre retrospective study, patients with viraemia >500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

Safety and efficacy of a hydroxypropyl guar/polyethylene glycol/propylene glycol-based lubricant eye-drop in patients with dry eye.

PubMed

Labetoulle, Marc; Messmer, Elisabeth M; Pisella, Pierre-Jean; Ogundele, Abayomi; Baudouin, Christophe

2017-04-01

To demonstrate non-inferiority of a hydroxypropyl guar/polyethylene glycol/propylene glycol lubricating eye-drop (HPG/PEG/PG) compared with an osmoprotective carboxymethylcellulose/glycerine eye-drop (O/CMC) for ocular surface staining. This was a multicentre, randomised, observer-masked, parallel-group study. Adults with dry eye instilled HPG/PEG/PG/ or O/CMC 4 times daily for 35 days and then as needed through day 90. Total ocular surface staining (TOSS) score changes from baseline and Impact of Dry Eye on Everyday Life (IDEEL) treatment satisfaction module scores were assessed. Non-inferiority, based on TOSS score change from baseline, was concluded if the upper limit of the 2-sided CI was <2 units. Mean±SD patient age was 64.4±13.7 years; 94 patients were randomised to treatment (HPG/PEG/PG, n=46; O/CMC, n=48). Mean±SE TOSS score change from baseline to day 35 was -2.2±0.33 with HPG/PEG/PG and -1.7±0.47 with O/CMC (treatment difference, -0.47±0.47; p=0.38), and the non-inferiority criterion was met. IDEEL treatment satisfaction scores were similar between groups at day 35 and day 90. The most frequently reported adverse event was eye irritation (HPG/PEG/PG, n=2; O/CMC, n=3). HPG/PEG/PG and O/CMC reduced ocular surface damage, and HPG/PEG/PG was non-inferior to O/CMC. Both treatments were effective, convenient and well tolerated. NCT01863368, 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/.

Lack of efficacy of moclobemide or imipramine in the treatment of recurrent brief depression: results from an exploratory randomized, double-blind, placebo-controlled treatment study.

PubMed

Baldwin, David S; Green, Mary; Montgomery, Stuart A

2014-11-01

'Recurrent brief depression' (RBD) is a common, distressing and impairing depressive disorder for which there is no current proven pharmacological or psychological treatment. This multicentre, randomized, fixed-dose, parallel-group, placebo-controlled study of the reversible inhibitor of monoamine oxidase moclobemide (450 mg/day) and the tricyclic antidepressant imipramine (150 mg/day) evaluated the potential efficacy of active medication, when compared with placebo, in patients with recurrent brief depression, recruited in the mid-1990s. After a 2-4-week single-blind placebo run-in period, a total of 35 patients were randomized to receive double-blind medication for 4 months, but only 16 completed the active treatment period. An intention-to-treat analysis of the 34 evaluable patients found no evidence for the efficacy of moclobemide or imipramine, when compared with placebo, in significantly reducing the severity, duration or frequency of depressive episodes. A total of 28 patients experienced at least one adverse event, and four patients engaged in nonfatal self-harm. Limitations of the study include the small sample size and the high rate of participant withdrawal. The lack of efficacy of these antidepressant drugs and the previous finding of the lack of efficacy of the selective serotonin reuptake inhibitor fluoxetine together indicate that medications other than antidepressant drugs should be investigated as potential treatments for what remains a common, distressing and potentially hazardous condition.

Mindfulness based cognitive therapy versus treatment as usual in adults with attention deficit hyperactivity disorder (ADHD).

PubMed

Janssen, Lotte; Kan, Cornelis C; Carpentier, Pieter J; Sizoo, Bram; Hepark, Sevket; Grutters, Janneke; Donders, Rogier; Buitelaar, Jan K; Speckens, Anne E M

2015-09-15

Adults with attention deficit hyperactivity disorder (ADHD) often present with a lifelong pattern of core symptoms that is associated with impairments of functioning in daily life. This has a substantial personal and economic impact. In clinical practice there is a high need for additional or alternative interventions for existing treatments, usually consisting of pharmacotherapy and/or psycho-education. Although previous studies show preliminary evidence for the effectiveness of mindfulness-based interventions in reducing ADHD symptoms and improving executive functioning, these studies have methodological limitations. This study will take account of these limitations and will examine the effectiveness of Mindfulness Based Cognitive Therapy (MBCT) in further detail. A multi-centre, parallel-group, randomised controlled trial will be conducted in N = 120 adults with ADHD. Patients will be randomised to MBCT in addition to treatment as usual (TAU) or TAU alone. Assessments will take place at baseline and at three, six and nine months after baseline. Primary outcome measure will be severity of ADHD symptoms rated by a blinded clinician. Secondary outcome measures will be self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. In addition, a cost-effectiveness analysis will be conducted. This trial will offer valuable information about the clinical and cost-effectiveness of MBCT in addition to TAU compared to TAU alone in adults swith ADHD. ClinicalTrials.gov NCT02463396. Registered 8 June 2015.

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.

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

PubMed

Harji, Deena; Marshall, Helen; Gordon, Katie; Crow, Hannah; Hiley, Victoria; Burke, Dermot; Griffiths, Ben; Moriarty, Catherine; Twiddy, Maureen; O'Dwyer, John L; Verjee, Azmina; Brown, Julia; Sagar, Peter

2018-02-22

Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The results from the trial will be presented at national and international colorectal conferences and will be submitted for publication to peer-reviewed journals. ISRCTN15681041; 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.

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

PubMed

Senin, U; Abate, G; Fieschi, C; Gori, G; Guala, A; Marini, G; Villardita, C; Parnetti, L

1991-12-01

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol.

PubMed

Jauregui, Amale; Ponte, Joaquín; Salgueiro, Monika; Unanue, Saloa; Donaire, Carmen; Gómez, Maria Cruz; Burgos-Alonso, Natalia; Grandes, Gonzalo

2015-03-20

In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions in our geographical setting. NCT01907035 (July 22, 2013).

Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone.

PubMed

Terra, Steven G; Focht, Kristen; Davies, Melanie; Frias, Juan; Derosa, Giuseppe; Darekar, Amanda; Golm, Gregory; Johnson, Jeremy; Saur, Didier; Lauring, Brett; Dagogo-Jack, Sam

2017-05-01

To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes. This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26. At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were -0.99% and -1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P  < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia. Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy. © 2017 John Wiley & Sons Ltd.

Treating KSHV-Associated Multicentric Castleman Disease

Cancer.gov

In this study, patients with KSHV-associated multicentric Castleman disease will receive IV tocilizumab every other week for up to 12 weeks. Patients who do not benefit may go on to receive high-dose AZT and valganciclovir as well.

Exploring asynchronous brainstorming in large groups: a field comparison of serial and parallel subgroups.

PubMed

de Vreede, Gert-Jan; Briggs, Robert O; Reiter-Palmon, Roni

2010-04-01

The aim of this study was to compare the results of two different modes of using multiple groups (instead of one large group) to identify problems and develop solutions. Many of the complex problems facing organizations today require the use of very large groups or collaborations of groups from multiple organizations. There are many logistical problems associated with the use of such large groups, including the ability to bring everyone together at the same time and location. A field study involved two different organizations and compared productivity and satisfaction of group. The approaches included (a) multiple small groups, each completing the entire process from start to end and combining the results at the end (parallel mode); and (b) multiple subgroups, each building on the work provided by previous subgroups (serial mode). Groups using the serial mode produced more elaborations compared with parallel groups, whereas parallel groups produced more unique ideas compared with serial groups. No significant differences were found related to satisfaction with process and outcomes between the two modes. Preferred mode depends on the type of task facing the group. Parallel groups are more suited for tasks for which a variety of new ideas are needed, whereas serial groups are best suited when elaboration and in-depth thinking on the solution are required. Results of this research can guide the development of facilitated sessions of large groups or "teams of teams."

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self-adhesive 5-aminolaevulinic acid patch.

PubMed

Hauschild, Axel; Popp, Georg; Stockfleth, Eggert; Meyer, Karl-Gustav; Imberger, Dirk; Mohr, Peter; Itschert, Götz; Kaufmann, Roland; Neuber, Karsten; Frambach, Yvonne; Gollnick, Harald; Brunnert, Marcus; Stocker, Marcus; Ortland, Christoph; Karrer, Sigrid

2009-02-01

Photodynamic therapy (PDT) is increasingly used for the treatment of actinic keratosis (AK). To investigate both the efficacy of different application times and the safety of a novel patch (PD P 506 A) containing aminolaevulinic acid in the PDT of mild to moderate AK. Applications of PD P 506 A for 0.5, 1, 2 and 4 h were compared in a multicentre, randomized, blinded-observer, parallel-group study. After patch removal, study lesions were illuminated with red light (lambda(em) approximately 630 nm; 37 J/cm(2)). Study lesions were not pretreated (e.g. by curettage) prior to PDT. Efficacy was evaluated 4 and 8 weeks after treatment. Safety and tolerability were determined through laboratory analyses and documentation of both local reactions and adverse events. A total of 149 patients were initially enrolled. Of these, 140 patients (520 lesions) completed the study according to protocol. Eight weeks after treatment, 86% of the AK lesions (74% of the patients) treated with 4-h patch application showed complete clearance. The complete clearance rates of lesions (patients) for the 2-, 1- and 0.5-h treatment arms were 73% (47%), 72% (50%) and 51% (24%), respectively. Statistically, the 4-h application was identified as the 'best treatment'. Patients with clearance seemed to experience local reactions to a greater extent than patients without clearance. Local reactions to study treatments did not exceed the expected range. The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.

Efficacy and safety of nebivolol and valsartan as fixed-dose combination in hypertension: a randomised, multicentre study.

PubMed

Giles, Thomas D; Weber, Michael A; Basile, Jan; Gradman, Alan H; Bharucha, David B; Chen, Wei; Pattathil, Manoj

2014-05-31

The fixed-dose combination of any two antihypertensive drugs from different drug classes is typically more effective in reducing blood pressure than a dose increase of component monotherapy. We assessed the efficacy and safety of a fixed-dose combination of a vasodilating β blocker (nebivolol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension. We did an 8-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial at 401 US sites. Participants (age ≥18 years) with hypertension but with blood pressure less than 180/110 mm Hg were randomly assigned (2:2:2:2:2:2:2:1) by a 24-h interactive web response system in blocks of 15 to 4 weeks of double-blind treatment with nebivolol and valsartan fixed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or 10 and 160 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or placebo. Doses were doubled in weeks 5-8; results are reported according to the final dose. Participants and research staff were masked to treatment allocation. The primary and key secondary endpoints were changes from baseline to week 8 in diastolic and systolic blood pressure, respectively. The primary statistical comparison was between the highest fixed-dose combination dose and the highest monotherapy doses; lower doses were then compared if this comparison was positive (Hochberg method for multiple testing). Efficacy analyses were by intention to treat. Safety assessments included monitoring of adverse events. Continuous efficacy parameters were analysed using an ANCOVA model; binary outcomes were analysed using a logistic regression model. This study is registered with ClinicalTrials.gov, NCT01508026. Between Jan 6, 2012, and March 15, 2013, 4161 patients were randomly assigned (277 to placebo and 554-555 to each active comparator group), 4118 of whom were included in the primary analysis. At week 8, the fixed-dose combination 20 and 320 mg/day group had significantly greater reductions in diastolic blood pressure from baseline than both nebivolol 40 mg/day (least-squares mean difference -1·2 mm Hg, 95% CI -2·3 to -0·1; p=0·030) and valsartan 320 mg/day (-4·4 mm Hg, -5·4 to -3·3; p<0·0001); all other comparisons were also significant, favouring the fixed-dose combinations (all p<0·0001). All systolic blood pressure comparisons were also significant (all p<0·01). At least one treatment-emergent adverse event was experienced by 30-36% of participants in each group. Nebivolol and valsartan fixed-dose combination is an effective and well-tolerated treatment option for patients with hypertension. Forest Research Institute. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of SofZia-preserved travoprost and benzalkonium chloride-preserved latanoprost on the ocular surface -- a multicentre randomized single-masked study.

PubMed

Aihara, Makoto; Oshima, Hiromi; Araie, Makoto

2013-02-01

To assess the effect of SofZia-preserved travoprost on ocular surface conditions in comparison with benzalkonium chloride (BAK)-preserved latanoprost. A prospective randomized multicentre single-masked comparative study. Patients with open-angle glaucoma or ocular hypertension who had been treated with BAK-preserved latanoprost 0.005% (Xalatan(®) ) monotherapy for at least 3 months. Patients were enrolled at 23 facilities. Patients were randomly divided into the X-X group, continuous use of Xalatan(®) , or the X-T group, switching from Xalatan(®) to SofZia-preserved travoprost 0.004% (TravatanZ(®) ), and followed for 3 months. The superficial punctate keratopathy (SPK), conjunctival epitheliopathy, hyperaemia, tear break-up time (TBUT) and intraocular pressure (IOP) were examined for each patient in a masked manner. Changes in the frequency of keratoconjunctival epitheliopathy were evaluated 3 months after study initiation. Intra- and intergroup comparisons of changes in SPK, conjunctival epitheliopathy, hyperaemia, TBUT and IOP were also carried out. Two hundred twenty patients participated and 215 completed the 3-month study. The frequency of keratoconjunctival epitheliopathy significantly decreased in the X-T group (p = 0.036) and the intergroup difference was also significant (p = 0.001). SPK scores and TBUT were significantly improved in the X-T group (p = 0.034, 0.049), also with significant intergroup differences in the cornea excluding the inferior area and TBUT. There were no significant intergroup differences in changes of the hyperaemia scores and the IOP reduction. Switching to SofZia-preserved travoprost after BAK-preserved latanoprost resulted in a lower incidence of keratoconjunctival epitheliopathy, especially in the cornea, with no clinically relevant changes in hyperaemia and IOP. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Physical activity prescription by primary care nurses using health assets: Study design of a randomized controlled trial in patients with cardiovascular risk factors.

PubMed

Riera-Sampol, Aina; Tauler, Pedro; Bennasar-Veny, Miquel; Leiva, Alfonso; Artigues-Vives, Guillem; De Pedro-Gómez, Joan; Pericàs, Jordi; Moreno, Carlos; Arbos, Maite; Aguilo, Antoni

2017-09-01

To analyse the efficacy of a 12-month multifactorial intervention by primary care nurses in increasing adherence to physical activity prescription (150 min/week) in patients with two or more cardiovascular risk factors and with cardiovascular risk up to 15% determined by the REGICOR equation. In Spain, cardiovascular diseases are responsible for 30.5% of deaths. Regular physical activity decreases mortality risk due to cardiovascular diseases but the effectiveness of physical activity prescription in routine in primary care settings has been shown to be low. Multicentre, single-blind, parallel randomized (in two different branches) clinical trial. At least 368 participants will be recruited (184 control and 184 intervention), to show an 8% increase in adherence to the physical activity prescription (1.2% control group and 9.2% intervention group). Participants will be patients aged 35-75 years with at least two cardiovascular risk factors and with a cardiovascular risk of up to 15% measured using the Framingham-REGICOR equation. Intervention will be performed throughout baseline and three follow-up visits. A motivational interview, the trans-theoretical stages of changes of Prochaska and DiClemente and an individualized prescription of physical exercise using physical activity assets will be used in the intervention. Data will be collected at baseline and after the 1-year intervention. The present study will allow us to find out whether this brief multifactorial intervention induces greater adherence to physical activity prescription than usual practice, improving the quality of patient care. International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN76069254. Protocol version 1.1, 6 July 2015. © 2017 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.

Efficacy of a videoconferencing intervention compared with standard postnatal care at primary care health centres in Catalonia.

PubMed

Seguranyes, Gloria; Costa, Dolors; Fuentelsaz-Gallego, Carmen; Beneit, Juan Vicente; Carabantes, David; Gómez-Moreno, Carme; Palacio-Tauste, Alicia; Pauli, Angels; Abella, Montserrat

2014-06-01

to evaluate the efficacy of an intervention combining videoconferencing and telephone contact compared to standard post partum care of recent mothers attending health centres in Catalonia were recorded. multicentre, randomised parallel controlled clinical trial. 1598 post partum women with Internet access attending eight 'Attention to Sexual and Reproductive Health' (Catalan acronym ASSIR) units at Primary Health Care centres, in Catalonia (Spain). at each of the eight ASSIR units, 100 women were randomly assigned to the intervention group (IG) and 100 to the control group (CG). Women in the IG could consult midwives by videoconference or telephone and could also receive standard care. Women in the control group received standard care from midwives at their health centres or at home. number and type of visits, reasons for consultation, type of feeding at six weeks and women's satisfaction with the intervention on a scale of 1 to 5. 1401 women were studied (80.9% of the initial sample), 683 in the IG and 718 in the CG. Two hundred and seventy-six women (40.4%) used videoconferencing or telephone in the IG. The mean total visits, virtual and face-to-face, was higher in IG women than in controls (2.74 versus 1.22). IG women made fewer visits to the health centre (mean=1) than CG women (mean=1.17). Both differences were statistically significant, with p<0.001 and p=0.002 respectively. The prevalence of breast feeding was similar in the two groups (IG 64.5%, and CG 65.4%). The mean overall satisfaction of women with midwife care was very high in both groups (IG 4.77, CG 4.76). virtual care via videoconferencing is effective for post partum women. It reduces the number of health centre visits and allows mothers to consult health staff immediately and from their own home. © 2013 Elsevier Ltd. All rights reserved.

Comparison of COAP and UW-19 protocols for dogs with multicentric lymphoma.

PubMed

Hosoya, Kenji; Kisseberth, William C; Lord, Linda K; Alvarez, Francisco J; Lara-Garcia, Ana; Kosarek, Carrie E; London, Cheryl A; Couto, C Guillermo

2007-01-01

Various chemotherapy protocols for treating lymphoma in dogs have been published; however, comparison of protocols from different studies is difficult, especially when evaluating survival time and toxicoses. The choice of COAP (C, cyclophosphamide; O, vincristine; A, cytosine arabinoside; P, prednisone) and a modified University of Wisconsin 19-week (UW-19) induction protocol has no influence on overall survival times in dogs with lymphoma. One hundred and one dogs with multicentric lymphoma. Retrospective study (2001-2006). Dogs induced with either an 8-week COP-based protocol (C, cyclophosphamide; O, vincristine; and P, prednisone) with maintenance therapy (COAP group) or a 19-week CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisone) based protocol (UW-19 group) were compared in terms of the duration of first remission, survival time, toxicoses, and cost. There were 71 dogs in the COAP group and 30 dogs in the UW-19 group. Various protocols were used after the first relapse. The median duration of the first remission for the COAP and UW-19 groups were 94 days (range, 6-356 days) and 174 days (28-438 days), respectively (P < .01). The median survival times for dogs in the COAP and UW-19 groups were 309 days (6-620 days) and 275 days (70-1102+ days), respectively (P = .09). Dogs in the COAP group had a hazard ratio of 1.9 (95% CI 1.1-3.4) for death relative to the UW-19 group (P = .03), after controlling for the confounders (World Health Organization clinical stage, age, sex, use of doxorubicin during reinduction). The severity of neutropenia and gastrointestinal toxicoses were significantly higher in the UW-19 group than in the COAP group (P = .01 and P < .01, respectively). Use of a long-term doxorubicin-containing sequential combination chemotherapy protocol is associated with a decreased risk of relapse and death relative to a non-doxorubicin-containing protocol.

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

PubMed

de Vos, Cecile C; Meier, Kaare; Zaalberg, Paul Brocades; Nijhuis, Harold J A; Duyvendak, Wim; Vesper, Jan; Enggaard, Thomas P; Lenders, Mathieu W P M

2014-11-01

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

A Randomized Controlled Trial of the Impact of a Family-Based Adolescent Depression Intervention on both Youth and Parent Mental Health Outcomes.

PubMed

Poole, Lucinda A; Knight, Tess; Toumbourou, John W; Lubman, Dan I; Bertino, Melanie D; Lewis, Andrew J

2018-01-01

This paper presents findings from a multi-centre, double-blind, randomized controlled trial that tested the hypothesis that parent and youth mental health improvements would be superior in a family-based intervention for adolescent depression (BEST MOOD) compared to a treatment-as-usual supportive parenting program (PAST). Eligible participants were families with a young person aged between 12 and 18 years who met diagnostic criteria for a depressive disorder (major, minor or dysthymic). Participating families (N = 64; 73.4% of youth were female) were recruited in Victoria, Australia and allocated to treatment condition using a block randomization procedure (parallel design) with two levels of blinding. This paper reports on the trial's secondary outcomes on youth and parent mental health. General linear mixed models were used to examine the longitudinal effect of treatment group on outcome. Data were analyzed according to intention-to-treat; 31 families were analyzed in BEST MOOD, and 33 families in PAST. Parents in the BEST MOOD group experienced significantly greater reductions in stress and depressive symptoms than parents in the PAST group at 3-month follow-up. A greater reduction in parental anxiety was observed in the BEST MOOD group (d = 0.35) compared with PAST (d = 0.02), although the between-group difference was not significant. Both groups of youth showed similar levels of improvement in depressive symptoms at post-treatment (d = 0.83 and 0.80 respectively), which were largely sustained at a 3-month follow-up. The family-based BEST MOOD intervention appeared superior to treatment-as-usual (PAST) in demonstrating greater reductions in parental stress and depression. Both interventions produced large reductions in youth depressive symptoms.

A multicentre prospective study of Guillain-Barré syndrome in Japan: a focus on the incidence of subtypes.

PubMed

Mitsui, Yoshiyuki; Kusunoki, Susumu; Arimura, Kimiyoshi; Kaji, Ryuji; Kanda, Takashi; Kuwabara, Satoshi; Sonoo, Masahiro; Takada, Kazuo

2015-01-01

Guillain-Barré Syndrome (GBS) is classified into the two major subtypes; acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Previous studies have suggested that AIDP is predominant and AMAN is rare in Western countries, whereas AMAN is not always uncommon in East Asia. We aimed to clarify the incidence of the subtypes of GBS in Japan. We performed a prospective multicentre survey over 3 years (2007-2010). Clinical and electrophysiological findings were collected from 184 patients with GBS in 23 tertiary neurology institutes. Anti-ganglioside antibodies were measured by ELISA. We also surveyed the incidence of Fisher syndrome (FS). By electrodiagnostic criteria of Ho et al, patients were classified as having AIDP (40%), or AMAN (22%), or unclassified (38%). Anti-GM1 IgG antibodies were found for 47% of AMAN patients, and 18% of AIDP patients (p<0.001). There were no specific regional trends of the electrodiagnosis and anti-GM1 positivity. During the same study period, 79 patients with FS were identified; the percentage of FS cases out of all cases (FS/(GBS+FS)) was 26%. The frequency of GBS patients with the electrodiagnosis of AMAN by single nerve conduction studies is approximately 20% in Japan, and the AMAN pattern is closely associated with anti-GM1 antibodies. The incidence of FS appears to be much higher in Japan than in Western countries. 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.

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years

PubMed Central

2014-01-01

Background Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. Methods/Design This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. Discussion This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Trial registration Current Controlled Trials ISRCTN04180738. PMID:24621174

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.

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

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial.

PubMed

Neuschwander-Tetri, Brent A; Loomba, Rohit; Sanyal, Arun J; Lavine, Joel E; Van Natta, Mark L; Abdelmalek, Manal F; Chalasani, Naga; Dasarathy, Srinivasan; Diehl, Anna Mae; Hameed, Bilal; Kowdley, Kris V; McCullough, Arthur; Terrault, Norah; Clark, Jeanne M; Tonascia, James; Brunt, Elizabeth M; Kleiner, David E; Doo, Edward

2015-03-14

The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis. We did a multicentre, double-blind, placebo-controlled, parallel group, randomised clinical trial at medical centres in the USA in patients with non-cirrhotic, non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally (25 mg daily) or placebo for 72 weeks. Patients were randomly assigned 1:1 using a computer-generated, centrally administered procedure, stratified by clinical centre and diabetes status. The primary outcome measure was improvement in centrally scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment. A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment (72 weeks) biopsies supported the decision to continue the trial (relative change in alanine aminotransferase -24%, 95% CI -45 to -3). A planned interim analysis of the primary outcome showed improved efficacy of obeticholic acid (p=0·0024) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients, but to continue the trial to obtain the 24-week post-treatment measures. Analyses were done by intention-to-treat. This trial was registered with ClinicalTrials.gov, number NCT01265498. Between March 16, 2011, and Dec 3, 2012, 141 patients were randomly assigned to receive obeticholic acid and 142 to placebo. 50 (45%) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 (21%) of 109 such patients in the placebo group (relative risk 1·9, 95% CI 1·3 to 2·8; p=0·0002). 33 (23%) of 141 patients in the obeticholic acid developed pruritus compared with nine (6%) of 142 in the placebo group. Obeticholic acid improved the histological features of non-alcoholic steatohepatitis, but its long-term benefits and safety need further clarification. National Institute of Diabetes and Digestive and Kidney Diseases, Intercept Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multi-centric universal pseudonymisation for secondary use of the EHR.

PubMed

Lo Iacono, Luigi

2007-01-01

This paper discusses the importance of protecting the privacy of patient data kept in an Electronic Health Record (EHR) in the case, where it leaves the control- and protection-sphere of the health care realm for secondary uses such as clinical or epidemiological research projects, health care research, assessment of treatment quality or economic assessments. The paper focuses on multi-centric studies, where various data sources are linked together using Grid technologies. It introduces a pseudonymisation system which enables a multi-centric universal pseudonymisation, meaning that a patient's identity will result in the same pseudonym, regardless of which participating study center the patient data is collected.

A national registry for juvenile dermatomyositis and other paediatric idiopathic inflammatory myopathies: 10 years' experience; the Juvenile Dermatomyositis National (UK and Ireland) Cohort Biomarker Study and Repository for Idiopathic Inflammatory Myopathies

PubMed Central

Martin, Neil; Krol, Petra; Smith, Sally; Murray, Kevin; Pilkington, Clarissa A.; Davidson, Joyce E.

2011-01-01

Objectives. The paediatric idiopathic inflammatory myopathies (IIMs) are a group of rare chronic inflammatory disorders of childhood, affecting muscle, skin and other organs. There is a severe lack of evidence base for current treatment protocols in juvenile myositis. The rarity of these conditions means that multicentre collaboration is vital to facilitate studies of pathogenesis, treatment and disease outcomes. We have established a national registry and repository for childhood IIM, which aims to improve knowledge, facilitate research and clinical trials, and ultimately to improve outcomes for these patients. Methods. A UK-wide network of centres and research group was established to contribute to the study. Standardized patient assessment, data collection forms and sample protocols were agreed. The Biobank includes collection of peripheral blood mononuclear cells, serum, genomic DNA and biopsy material. An independent steering committee was established to oversee the use of data/samples. Centre training was provided for patient assessment, data collection and entry. Results. Ten years after inception, the study has recruited 285 children, of which 258 have JDM or juvenile PM; 86% of the cases have contributed the biological samples. Serial sampling linked directly to the clinical database makes this a highly valuable resource. The study has been a platform for 20 sub-studies and attracted considerable funding support. Assessment of children with myositis in contributing centres has changed through participation in this study. Conclusions. This establishment of a multicentre registry and Biobank has facilitated research and contributed to progress in the management of a complex group of rare muscloskeletal conditions. PMID:20823094

Reporting of participant flow diagrams in published reports of randomized trials

PubMed Central

2011-01-01

Background Reporting of the flow of participants through each stage of a randomized trial is essential to assess the generalisability and validity of its results. We assessed the type and completeness of information reported in CONSORT (Consolidated Standards of Reporting Trials) flow diagrams published in current reports of randomized trials. Methods A cross sectional review of all primary reports of randomized trials which included a CONSORT flow diagram indexed in PubMed core clinical journals (2009). We assessed the proportion of parallel group trial publications reporting specific items recommended by CONSORT for inclusion in a flow diagram. Results Of 469 primary reports of randomized trials, 263 (56%) included a CONSORT flow diagram of which 89% (237/263) were published in a CONSORT endorsing journal. Reports published in CONSORT endorsing journals were more likely to include a flow diagram (62%; 237/380 versus 29%; 26/89). Ninety percent (236/263) of reports which included a flow diagram had a parallel group design, of which 49% (116/236) evaluated drug interventions, 58% (137/236) were multicentre, and 79% (187/236) compared two study groups, with a median sample size of 213 participants. Eighty-one percent (191/236) reported the overall number of participants assessed for eligibility, 71% (168/236) the number excluded prior to randomization and 98% (231/236) the overall number randomized. Reasons for exclusion prior to randomization were more poorly reported. Ninety-four percent (223/236) reported the number of participants allocated to each arm of the trial. However, only 40% (95/236) reported the number who actually received the allocated intervention, 67% (158/236) the number lost to follow up in each arm of the trial, 61% (145/236) whether participants discontinued the intervention during the trial and 54% (128/236) the number included in the main analysis. Conclusions Over half of published reports of randomized trials included a diagram showing the flow of participants through the trial. However, information was often missing from published flow diagrams, even in articles published in CONSORT endorsing journals. If important information is not reported it can be difficult and sometimes impossible to know if the conclusions of that trial are justified by the data presented. PMID:22141446

The effect of a perioperative ketamine infusion on the incidence of chronic postsurgical pain-a pilot study.

PubMed

Peyton, P J; Wu, C; Jacobson, T; Hogg, M; Zia, F; Leslie, K

2017-07-01

Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P =0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range, IQR]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.

Effectiveness of a multifactorial falls prevention program in community-dwelling older people when compared to usual care: study protocol for a randomised controlled trial (Prevquedas Brazil).

PubMed

de Negreiros Cabral, Kelem; Perracini, Monica Rodrigues; Soares, Aline Thomaz; de Cristo Stein, Francine; Sera, Celisa Tiemi Nakagawa; Tiedemann, Anne; Sherrington, Cathie; Filho, Wilson Jacob; Paschoal, Sérgio Márcio Pacheco

2013-03-15

Falling in older age is a major public health concern due to its costly and disabling consequences. However very few randomised controlled trials (RCTs) have been conducted in developing countries, in which population ageing is expected to be particularly substantial in coming years. This article describes the design of an RCT to evaluate the effectiveness of a multifactorial falls prevention program in reducing the rate of falls in community-dwelling older people. Multicentre parallel-group RCT involving 612 community-dwelling men and women aged 60 years and over, who have fallen at least once in the previous year. Participants will be recruited in multiple settings in Sao Paulo, Brazil and will be randomly allocated to a control group or an intervention group. The usual care control group will undergo a fall risk factor assessment and be referred to their clinicians with the risk assessment report so that individual modifiable risk factors can be managed without any specific guidance. The intervention group will receive a 12-week Multifactorial Falls Prevention Program consisting of: an individualised medical management of modifiable risk factors, a group-based, supervised balance training exercise program plus an unsupervised home-based exercise program, an educational/behavioral intervention. Both groups will receive a leaflet containing general information about fall prevention strategies. Primary outcome measures will be the rate of falls and the proportion of fallers recorded by monthly falls diaries and telephone calls over a 12 month period. Secondary outcomes measures will include risk of falling, fall-related self-efficacy score, measures of balance, mobility and strength, fall-related health services use and independence with daily tasks. Data will be analysed using the intention-to-treat principle.The incidence of falls in the intervention and control groups will be calculated and compared using negative binomial regression analysis. This study is the first trial to be conducted in Brazil to evaluate the effectiveness of an intervention to prevent falls. If proven to reduce falls this study has the potential to benefit older adults and assist health care practitioners and policy makers to implement and promote effective falls prevention interventions. ClinicalTrials.gov (NCT01698580).

Affect school and script analysis versus basic body awareness therapy in the treatment of psychological symptoms in patients with diabetes and high HbA1c concentrations: two study protocols for two randomized controlled trials.

PubMed

Melin, Eva O; Svensson, Ralph; Gustavsson, Sven-Åke; Winberg, Agneta; Denward-Olah, Ewa; Landin-Olsson, Mona; Thulesius, Hans O

2016-04-27

Depression is linked with alexithymia, anxiety, high HbA1c concentrations, disturbances of cortisol secretion, increased prevalence of diabetes complications and all-cause mortality. The psycho-educational method 'affect school with script analysis' and the mind-body therapy 'basic body awareness treatment' will be trialled in patients with diabetes, high HbA1c concentrations and psychological symptoms. The primary outcome measure is change in symptoms of depression. Secondary outcome measures are changes in HbA1c concentrations, midnight salivary cortisol concentration, symptoms of alexithymia, anxiety, self-image measures, use of antidepressants, incidence of diabetes complications and mortality. Two studies will be performed. Study I is an open-labeled parallel-group study with a two-arm randomized controlled trial design. Patients are randomized to either affect school with script analysis or to basic body awareness treatment. According to power calculations, 64 persons are required in each intervention arm at the last follow-up session. Patients with type 1 or type 2 diabetes were recruited from one hospital diabetes outpatient clinic in 2009. The trial will be completed in 2016. Study II is a multicentre open-labeled parallel-group three-arm randomized controlled trial. Patients will be randomized to affect school with script analysis, to basic body awareness treatment, or to treatment as usual. Power calculations show that 70 persons are required in each arm at the last follow-up session. Patients with type 2 diabetes will be recruited from primary care. This study will start in 2016 and finish in 2023. For both studies, the inclusion criteria are: HbA1c concentration ≥62.5 mmol/mol; depression, alexithymia, anxiety or a negative self-image; age 18-59 years; and diabetes duration ≥1 year. The exclusion criteria are pregnancy, severe comorbidities, cognitive deficiencies or inadequate Swedish. Depression, anxiety, alexithymia and self-image are assessed using self-report instruments. HbA1c concentration, midnight salivary cortisol concentration, blood pressure, serum lipid concentrations and anthropometrics are measured. Data are collected from computerized medical records and the Swedish national diabetes and causes of death registers. Whether the "affect school with script analysis" will reduce psychological symptoms, increase emotional awareness and improve diabetes related factors will be tried, and compared to "basic body awareness treatment" and treatment as usual. ClinicalTrials.gov: NCT01714986.

The impact of DECISION+2 on patient intention to engage in shared decision making: secondary analysis of a multicentre clustered randomized trial.

PubMed

Couët, Nicolas; Labrecque, Michel; Robitaille, Hubert; Turcotte, Stéphane; Légaré, France

2015-12-01

Training health professionals in shared decision making (SDM) may influence their patients' intention to engage in SDM. To assess the impact of DECISION+2, a SDM training programme for family physicians about the use of antibiotics to treat acute respiratory infections (ARIs), on their patients' intention to engage in SDM in future consultations. Secondary analysis of a multicentre clustered randomized trial. Three hundred and fifty-nine patients consulting family physicians about an ARI in nine family practice teaching units (FPTUs). DECISION+2 (two-hour online tutorial, two-hour workshop, and decision support tools) was offered in the experimental group (five FPTUs, 162 physicians, 181 patients). Usual care was provided in the control group (four FPTUs, 108 physicians, 178 patients). Change in patients' intention scores (range -3 to +3) between pre- and post-consultation. The mean ± SD [median] scores of intention to engage in SDM were high in both study groups before consultation (DECISION+2 group: 1.4 ± 1.0 [1.7]; control group: 1.5 ± 1.1 [1.7]) and increased in both groups after consultation (DECISION+2 group: 2.1 ± 1.1 [2.7]; control group: 1.9 ± 1.2 [2.3]). Change of intention, classified as either increased, stable or decreased, was not statistically associated with the exposure to the DECISION+2 programme after adjusting for the cluster design (proportional odds ratio = 1.5; 95% confidence interval = 0.8-3.0). DECISION+2 had no significant impact on patients' intention to engage in SDM for choosing to use antibiotics or not to treat an ARI in future consultations. Patient-targeted interventions may be necessary to achieve this purpose. © 2014 John Wiley & Sons Ltd.

Comparing reliabilities of strip and conventional patch testing.

PubMed

Dickel, Heinrich; Geier, Johannes; Kreft, Burkhard; Pfützner, Wolfgang; Kuss, Oliver

2017-06-01

The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing. To estimate the parallel-test reliability of the strip patch test as compared with the conventional patch test. In this multicentre, prospective, randomized, investigator-blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers ® on Scanpor ® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient. Parallel-test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: -8% to 26%) for nickel sulfate and 23% (95%CI: -16% to 63%) for potassium dichromate, both favouring the strip patch test. The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

PubMed

Domènech, Eugeni; Panés, Julián; Hinojosa, Joaquín; Annese, Vito; Magro, Fernando; Sturniolo, Giacomo Carlo; Bossa, Fabrizio; Fernández, Francisco; González-Conde, Benito; García-Sánchez, Valle; Dignass, Axel; Herrera, José Manuel; Cabriada, José Luis; Guardiola, Jordi; Vecchi, Maurizio; Portela, Francisco; Ginard, Daniel

2018-05-25

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

PubMed

Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; De Soyza, Anthony; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

2017-07-01

The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration April 4, 2014). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study.

PubMed

Kubo, Satoshi; Yamaoka, Kunihiro; Amano, Koichi; Nagano, Shuji; Tohma, Shigeto; Suematsu, Eiichi; Nagasawa, Hayato; Iwata, Kanako; Tanaka, Yoshiya

2017-08-01

To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effectiveness of osteopathic manipulative treatment in neonatal intensive care units: protocol for a multicentre randomised clinical trial

PubMed Central

Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; D'Incecco, Carmine; Fusilli, Paola; Perri, Paolo Francesco; Tubaldi, Lucia; Barlafante, Gina

2013-01-01

Introduction Neonatal care has been considered as one of the first priorities for improving quality of life in children. In 2010, 10% of babies were born prematurely influencing national healthcare policies, economic action plans and political decisions. The use of complementary medicine has been applied to the care of newborns. One previous study documented the positive effect of osteopathic manipulative treatment (OMT) in reducing newborns’ length of stay (LOS). Aim of this multicentre randomised controlled trial is to examine the association between OMT and LOS across three neonatal intensive care units (NICUs). Methods and analysis 690 preterm infants will be recruited from three secondary and tertiary NICUs from north and central Italy and allocated into two groups, using permuted-block randomisation. The two groups will receive standard medical care and OMT will be applied, twice a week, to the experimental group only. Outcome assessors will be blinded of study design and group allocation. The primary outcome is the mean difference in days between discharge and entry. Secondary outcomes are difference in daily weight gain, number of episodes of vomit, regurgitation, stooling, use of enema, time to full enteral feeding and NICU costs. Statistical analyses will take into account the intention-to-treat method. Missing data will be handled using last observation carried forward (LOCF) imputation technique. Ethics and dissemination Written informed consent will be obtained from parents or legal guardians at study enrolment. The trial has been approved by the ethical committee of Macerata hospital (n°22/int./CEI/27239) and it is under review by the other regional ethics committees. Results Dissemination of results from this trial will be through scientific medical journals and conferences. Trial registration This trial has been registered at http://www.clinicaltrials.org (identifier NCT01645137). PMID:23430598

CD56‐positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer

PubMed Central

Assaf, Chalid; Gellrich, Sylke; Whittaker, Sean; Robson, Alistair; Cerroni, Lorenzo; Massone, Cesare; Kerl, Helmut; Rose, Christian; Chott, Andreas; Chimenti, Sergio; Hallermann, Christian; Petrella, Tony; Wechsler, Janine; Bagot, Martine; Hummel, Michael; Bullani‐Kerl, Katrin; Bekkenk, Marcel W; Kempf, Werner; Meijer, Chris J L M; Willemze, Rein; Sterry, Wolfram

2007-01-01

Background Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. Methods A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. Results Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal‐type extranodal natural killer/T‐cell lymphoma; and (4) “classical” cases of cutaneous T‐cell lymphoma (CTCL) with co‐expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2–72 months), whereas all patients with CD56+ CTCL were alive at the last follow‐up. Conclusion Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders. PMID:17018683

The EULAR Scleroderma Trials and Research Group (EUSTAR): an international framework for accelerating scleroderma research.

PubMed

Tyndall, Alan; Ladner, Ulf M; Matucci-Cerinic, Marco

2008-11-01

Systemic sclerosis has a complex pathogenesis and a multifaceted clinical spectrum without a specific treatment. Under the auspices of the European League Against Rheumatism, the European League Against Rheumatism Scleroderma Trials And Research group (EUSTAR) has been founded in Europe to foster the study of systemic sclerosis with the aim of achieving equality of assessment and care of systemic sclerosis patients throughout the world according to evidence-based principles. EUSTAR created the minimal essential data set, a simple two-page form with basic demographics and mostly yes/no answers to clinical and laboratory parameters, to track patients throughout Europe. Currently, over 7000 patients are registered from 150 centres in four continents, and several articles have been published with the data generated by the minimal essential data set. A commitment of EUSTAR is also to teaching and educating, and for this reason there are two teaching courses and a third is planned for early in 2009. These courses have built international networks among young investigators improving the quality of multicentre clinical trials. EUSTAR has organized several rounds of 'teach the teachers' to further standardize the skin scoring. EUSTAR activities have extended beyond European borders, and EUSTAR now includes experts from several nations. The growth of data and biomaterial might ensure many further fruitful multicentre studies, but the financial sustainability of EUSTAR remains an issue that may jeopardize the existence of this group as well as that of other organizations in the world.

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.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic.

PubMed

Roberts, Jason A; De Waele, Jan J; Dimopoulos, George; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C; Lipman, Jeffrey

2012-07-06

The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals) on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study) is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol. DALI will recruit over 500 patients administered a wide range of either beta-lactam or glycopeptide antibiotics or triazole or echinocandin antifungals in a pharmacokinetic point-prevalence study. It is anticipated that over 60 European intensive care units (ICUs) will participate. The primary aim will be to determine whether contemporary antibiotic dosing for critically ill patients achieves plasma concentrations associated with maximal activity. Secondary aims will compare antibiotic pharmacokinetic exposures with patient outcome and will describe the population pharmacokinetics of the antibiotics included. Various subgroup analyses will be conducted to determine patient groups that may be at risk of very low or very high concentrations of antibiotics. The DALI study should inform clinicians of the potential clinical advantages of achieving certain antibiotic pharmacokinetic exposures in infected critically ill patients.

Partial Tenon’s capsule resection with adjunctive mitomycin C in Ahmed glaucoma valve implant surgery

PubMed Central

Susanna, R

2003-01-01

Aim: To verify if partial intraoperative Tenon’s capsule resection (PTCR) with adjunctive mitomycin C is effective in developing thin, avascular blebs in eyes undergoing Ahmed glaucoma valve insertion, and to assess the efficacy and safety of this procedure. Methods: A multicentre, prospective, alternating case assignment, investigator unmasked, parallel group, comparative interventional study was conducted in four Latin American countries (Argentina, Brazil, Colombia, and Peru). Ahmed glaucoma valve implant insertion with PTCR (group A) and without PCTR (group B) was performed in neovascular glaucomatous eyes without previous surgery. Adjunctive mitomycin C (MMC) was used in both groups. Patients were examined 1 day, 10 days, 1 month, 2 months, 3 months, 6 months, and 1 year following the surgery. Intraocular pressure (IOP) and the appearance of the bleb were evaluated at each examination. Appearance of the bleb was classified at both the 1 month mark and last examinations into one of three groups: flat and vascularised; elevated avascular; or elevated and not avascular. Results: 92 eyes from 92 patients were included in the study. The preoperative mean IOP was 50.0 (SD 10.5) mm Hg in group A and 48.4 (11.7) in group B (p>0.05). Statistically significant IOP reductions were observed at all periods of follow up. 12 months after surgery, the mean IOP was 17.2 (5.0) mm Hg in group A and 18.3 (8.7) mm Hg in group B (p>0.05). A hypertensive phase occurred in 40.0% in group A and in 46.8% in group B (p>0.05). At the 1 month and the final follow up, the blebs in all eyes were considered elevated and not avascular. The success rate (IOP⩽21 mm Hg) at 1 year after surgery was 70.4% in group A and 77.7% in group B (p>0.05). Overall, 74.2% of the patients achieved an IOP ⩽21 mm Hg and 55.2% an IOP⩽17 mm Hg, with or without additional medication administered to lower IOP. The incidence of complications was similar in both groups. Conclusions: In eyes undergoing Ahmed valve implantation for neovascular glaucoma, PCTR with MMC augmentation showed no additional benefits or complications over MMC augmentation alone; no avascular bleb was obtained with this technique. The incidence of a hypertensive phase was lower than reported in previous studies. PMID:12881343

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma.

PubMed

Daters, A T; Mauldin, G E; Mauldin, G N; Brodsky, E M; Post, G S

2010-03-01

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

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

A multicentre, double-masked, randomized, controlled trial assessing the effect of oral supplementation of omega-3 and omega-6 fatty acids on a conjunctival inflammatory marker in dry eye patients.

PubMed

Brignole-Baudouin, Françoise; Baudouin, Christophe; Aragona, Pasquale; Rolando, Maurizio; Labetoulle, Marc; Pisella, Pierre Jean; Barabino, Stefano; Siou-Mermet, Raphaele; Creuzot-Garcher, Catherine

2011-11-01

To determine whether oral supplementation with omega-3 and omega-6 fatty acids can reduce conjunctival epithelium expression of the inflammatory marker human leucocyte antigen-DR (HLA-DR) in patients with dry eye syndrome (DES). This 3-month, double-masked, parallel-group, controlled study was conducted in nine centres, in France and Italy. Eligible adult patients with mild to moderate DES were randomized to receive a placebo containing medium-chain triglycerides or treatment supplement containing omega-3 and omega-6 fatty acids, vitamins and zinc. Treatment regimen was three capsules daily. Impression cytology (IC) was performed at baseline and at month 3 to assess the percentage of cells expressing HLA-DR and to evaluate fluorescence intensity, an alternate measure of HLA-DR. Dry eye symptoms and objective signs were also evaluated. Analyses were performed on the full analysis set (FAS) and per-protocol set (PPS). In total, 138 patients were randomized; 121 patients with available IC were included in the FAS, and of these, 106 patients had no major protocol deviations (PPS). In the PPS, there was a significant reduction in the percentage of HLA-DR-positive cells in the fatty acids group (p = 0.021). Expression of HLA-DR as measured by fluorescence intensity quantification was also significantly reduced in the fatty acids group [FAS (p = 0.041); PPS (p = 0.017)]. No significant difference was found for the signs and symptoms, but there was a tendency for improvement in patients receiving the fatty acids treatment. This study demonstrates that supplementation with omega-3 and omega-6 fatty acids can reduce expression of HLA-DR conjunctival inflammatory marker and may help improve DES symptoms. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Protocol for a multicentre, prospective, population-based cohort study of variation in practice of cholecystectomy and surgical outcomes (The CholeS study).

PubMed

Vohra, Ravinder S; Spreadborough, Philip; Johnstone, Marianne; Marriott, Paul; Bhangu, Aneel; Alderson, Derek; Morton, Dion G; Griffiths, Ewen A

2015-01-12

Cholecystectomy is one of the most common general surgical operations performed. Despite level one evidence supporting the role of cholecystectomy in the management of specific gallbladder diseases, practice varies between surgeons and hospitals. It is unknown whether these variations account for the differences in surgical outcomes seen in population-level retrospective data sets. This study aims to investigate surgical outcomes following acute, elective and delayed cholecystectomies in a multicentre, contemporary, prospective, population-based cohort. UK and Irish hospitals performing cholecystectomies will be recruited utilising trainee-led research collaboratives. Two months of consecutive, adult patient data will be included. The primary outcome measure of all-cause 30-day readmission rate will be used in this study. Thirty-day complication rates, bile leak rate, common bile duct injury, conversion to open surgery, duration of surgery and length of stay will be measured as secondary outcomes. Prospective data on over 8000 procedures is anticipated. Individual hospitals will be surveyed to determine local policies and service provision. Variations in outcomes will be investigated using regression modelling to adjust for confounders. Research ethics approval is not required for this study and has been confirmed by the online National Research Ethics Service (NRES) decision tool. This novel study will investigate how hospital-level surgical provision can affect patient outcomes, using a cross-sectional methodology. The results are essential to inform commissioning groups and implement changes within the National Health Service (NHS). Dissemination of the study protocol is primarily through the trainee-led research collaboratives and the Association of Upper Gastrointestinal Surgeons (AUGIS). Individual centres will have access to their own results and the collective results of the study will be published in peer-reviewed journals and presented at relevant surgical conferences. 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.

EMBalance - validation of a decision support system in the early diagnostic evaluation and management plan formulation of balance disorders in primary care: study protocol of a feasibility randomised controlled trial.

PubMed

Rammazzo, Laura; Kikidis, Dimitris; Anwer, Amal; Macdonald, Nora; Kyrodimos, Efthymios; Maurer, Christoph; Wuyts, Floris; Luxon, Linda; Bibas, Athanasios; Bamiou, Doris-Eva

2016-09-05

Balance problems are caused by multiple factors and often lead to falls and related fractures, bringing large socio-economic costs. The complexity of balance control mechanisms, the lack of medical expertise, and the absence of specialised equipment contribute to the delayed or incorrect diagnosis and management ofthese patients. Advances in computer science have allowed the development of computer systems that support clinical diagnosis and treatment decisions based on individualised patient data. The aim of the EMBalance decision support system (DSS) is to support doctors facing this clinical challenge, to make a definitive diagnosis and implement an effective management plan. The EMBalance study will determine the accuracy of this supportive tool when used by non-specialist doctors. This study is funded by the European Union's Seventh Framework Programme. EMBalance is a proof-of-concept study designed as a non-commercial, international, multi-centre, single-blind, parallel-group randomised controlled trial to be carried out at four clinical sites in the United Kingdom, Germany, Greece and Belgium. The study is comprised of three stages: internal pilot, phase I (diagnosis) and stage II (management). For this purpose, 200 patients presenting with persistent dizziness (>3 months' duration) to primary care services will be randomised to either the intervention group (diagnostic assessment with the DSS) or a control group (diagnostic assessment without the DSS). Patients allocated to the intervention group will be assessed by a doctor with the support of the EMBalance DSS, while patients allocated to the control group will receive a visit as per standard practice. Ultimately, all patients' diagnoses and management plans will be certified by a consultant in neuro-otology. EMBalance is the first trial to test the accuracy of a DSS in both the diagnosis of and the management plan for vestibular disorders across the healthcare systems of four different countries. The EMBalance study is the result of a combined effort of engineers and physicians to develop an accurate tool to support non-specialist doctors, with no risk for the patient. This trial will provide reliable information about the benefits of implementing DSSs in primary care while supporting the feasibility of testing the EMBalance algorithms in further research. ClinicalTrials.gov NCT02704819 . Registered 29 February 2016.

Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P).

PubMed

Langley, R G; Papp, K; Gooderham, M; Zhang, L; Mallinckrodt, C; Agada, N; Blauvelt, A; Foley, P; Polzer, P

2018-06-01

Ixekizumab is an interleukin-17A antagonist approved for treatment of moderate-to-severe plaque psoriasis with a recommended 160-mg starting dose, then 80 mg every 2 weeks (Q2W) to week 12, and every 4 weeks (Q4W) thereafter. To evaluate continuous Q2W dosing over 52 weeks. In this phase III, multicentre, double-blinded, parallel-group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at week 52 in patients with moderate-to-severe plaque psoriasis randomized at a 2 : 1 : 1 ratio to continuous Q2W (n = 611), continuous Q4W (n = 310) or dose adjustment per protocol (Q4W/Q2W, n = 306), each with a 160-mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23?5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression. Co-primary end points were met at week 52: Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85·9% and 79·0%, respectively (P = 0·006), and static patient global assessment 0/1 responses for Q2W and Q4W dose groups were 78·6% and 70·6%, respectively (P = 0·005). Treatment-emergent and serious adverse events were comparable across dose groups. Ixekizumab Q2W had higher efficacy at week 52 than ixekizumab Q4W, with no increase in safety events. © 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

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

PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with pain from traumatic injuries: randomised trial.

PubMed

Smith, Jason E; Rockett, Mark; S, Siobhan Creanor; Squire, Rosalyn; Hayward, Chris; Ewings, Paul; Barton, Andy; Pritchard, Colin; Eyre, Victoria; Cocking, Laura; Benger, Jonathan

2015-06-21

To determine whether patient controlled analgesia (PCA) is better than routine care in patients presenting to emergency departments with moderate to severe pain from traumatic injuries. Pragmatic, multicentre, parallel group, randomised controlled trial. Five English hospitals. 200 adults (71% (n = 142) male), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe pain from traumatic injuries and were expected to be admitted to hospital for at least 12 hours. PCA (n = 99) or nurse titrated analgesia (treatment as usual; n = 101). The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate/severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management. 200 participants were included in the primary analyses. Mean total pain experienced was 47.2 (SD 21.9) for the treatment as usual group and 44.0 (24.0) for the PCA group. Adjusted analyses indicated slightly (but not statistically significantly) lower total pain experienced in the PCA group than in the routine care group (mean difference 2.7, 95% confidence interval -2.4 to 7.8). Participants allocated to PCA used more morphine in total than did participants in the treatment as usual group (mean 44.3 (23.2) v 27.2 (18.2) mg; mean difference 17.0, 11.3 to 22.7). PCA participants spent, on average, less time in moderate/severe pain (36.2% (31.0) v 44.1% (31.6)), but the difference was not statistically significant. A higher proportion of PCA participants reported being perfectly or very satisfied compared with the treatment as usual group (86% (78/91) v 76% (74/98)), but this was also not statistically significant. PCA provided no statistically significant reduction in pain compared with routine care for emergency department patients with traumatic injuries. Trial registration European Clinical Trials Database EudraCT2011-000194-31; Current Controlled Trials ISRCTN25343280. © Smith et al 2015.

The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study.

PubMed

Stanworth, R D; Akhtar, S; Channer, K S; Jones, T H

2014-02-01

The TIMES2 (testosterone replacement in hypogonadal men with either metabolic syndrome or type 2 diabetes) study reported beneficial effects of testosterone replacement therapy (TRT) on insulin resistance and other variables in men with diabetes or metabolic syndrome. The androgen receptor CAG repeat polymorphism (AR CAG) is known to affect stimulated AR activity and has been linked to various clinically relevant variables. To assess the role of AR CAG in the alteration of clinical response to TRT in the TIMES2 study. Subgroup analysis from a multicentre, randomised, double-blind, placebo-controlled and parallel group study. Outpatient study recruiting from secondary and primary care. A total of 139 men with hypogonadism and type 2 diabetes or metabolic syndrome, of which 73 received testosterone during the TIMES2 study. Testosterone 2% transdermal gel vs placebo. Regression coefficient of AR CAG from linear regression models for each variable. AR CAG was independently positively associated with change in fasting insulin, triglycerides and diastolic blood pressure during TRT with a trend to association with HOMA-IR - the primary outcome variable. There was a trend to negative association between AR CAG and change in PSA. There was no association of AR CAG with change in other glycaemic variables, other lipid variables or obesity. AR CAG affected the response of some variables to TRT in the TIMES2 study, although the association with HOMA-IR did not reach significance. Various factors may have limited the power of our study to detect the significant associations between AR CAG, testosterone levels and change in variables with testosterone treatment. Analysis of similar data sets from other clinical trials is warranted.

A mobile application of breast cancer e-support program versus routine Care in the treatment of Chinese women with breast cancer undergoing chemotherapy: study protocol for a randomized controlled trial.

PubMed

Zhu, Jiemin; Ebert, Lyn; Liu, Xiangyu; Chan, Sally Wai-Chi

2017-04-26

Women with breast cancer undergoing chemotherapy suffer from a number of symptoms and report receiving inadequate support from health care professionals. Innovative and easily accessible interventions are lacking. Breast Cancer e-Support is a mobile Application program (App) that provides patients with individually tailored information and a support group of peers and health care professionals. Breast Cancer e-Support aims to promote women's self-efficacy, social support and symptom management, thus improving their quality of life and psychological well-being. A single-blinded, multi-centre, randomised, 6-month, parallel-group superiority design will be used. Based on Bandura's self-efficacy theory and the social exchange theory, Breast Cancer e-Support has four modules: 1) a Learning forum; 2) a Discussion forum; 3) an Ask-the-Expert forum; and 4) a Personal Stories forum. Women with breast cancer (n = 108) who are commencing chemotherapy will be recruited from two university-affiliated hospitals in China. They will be randomly assigned to either control group that receives routine care or intervention group that receives routine care plus access to Breast Cancer e-Support program during their four cycles of chemotherapy. Self-efficacy, social support, symptom distress, quality of life, and anxiety and depression will be measured at baseline, then one week and 12 weeks post-intervention. This is the first study of its kind in China to evaluate the use of a mobile application intervention with a rigorous research design and theoretical framework. This study will contribute to evidence regarding the effectiveness of a theory-based mobile application to support women with breast cancer undergoing chemotherapy. The results should provide a better understanding of the role of self-efficacy and social support in reducing symptom distress and of the credibility of using a theoretical framework to develop internet-based interventions. The results will provide evidence to support the implementation of an innovative and easily accessible intervention that enhances health outcomes. ACTRN: ACTRN12616000639426 , Registered 17 May, 2016.

Positive and cost-effectiveness effect of spa therapy on the resumption of occupational and non-occupational activities in women in breast cancer remission: a French multicentre randomised controlled trial.

PubMed

Mourgues, Charline; Gerbaud, Laurent; Leger, Stéphanie; Auclair, Candy; Peyrol, Fleur; Blanquet, Marie; Kwiatkowski, Fabrice; Leger-Enreille, Anne; Bignon, Yves-Jean

2014-10-01

The main aim was to assess the effects of a spa treatment on the resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. A cost-effectiveness analysis (CEA) was also performed. A multicentre randomised controlled trial was carried out between 2008 and 2010 in the University Hospital of Auvergne and two private hospitals in Clermont-Ferrand, France. Eligible patients were women in complete breast cancer remission without contraindication for physical activities or cognitive disorders and a body mass index between 18.5 and 40 kg/m(2). The intervention group underwent spa treatment combined with consultation with dietician whereas the control underwent consultations with the dietician only. Of the 181 patients randomised, 92 and 89 were included in the intervention and the control groups, respectively. The CEA involved 90 patients, 42 from the intervention group and 48 from the control group. The main results showed a higher rate of resumption of occupational activities in the intervention group (p = 0.0025) and a positive effect of the intervention on the women's ability to perform occupational activities 12 months after the beginning of the study (p = 0.0014), and on their ability to perform family activities (p = 0.033). The stay in a thermal centre was cost-effective at 12 months. Spa treatment is a cost-effective strategy to improve resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prospective evaluation of the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) in a multicentre setting.

PubMed

Castel, V; García-Miguel, P; Cañete, A; Melero, C; Navajas, A; Ruíz-Jiménez, J I; Navarro, S; Badal, M D

1999-04-01

The aim of this study was to classify prospectively a series of neuroblastoma tumours according to the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) and to evaluate the difficulties and pitfalls involved in a multicentre setting. Each hospital provided their data for central review. The surgical procedures and their complications were reported. Kaplan-Meier estimates of survival and event-free survival were calculated according to stage and response to therapy. From June 1992 to December 1996, 194 patients were included in the study, with a mean age of 2 years. Initial studies were performed according to INSS recommendations without major problems. INSS stage was correctly applied to all patients except for 9 (95%). Post-operative complications were observed in 15 patients (8.3%). Response to therapy (INRC) was studied in 63 stage 4 patients, 11 of whom were not classified correctly (17%). Differences in survival according to stage (INSS) and group of response to therapy (INRC) were statistically significant (P < 0.001). In conclusion the INSS was easy to use and separated different prognostic groups. Surgical complications and mortality did not increase in this series because of using the INSS. The feasibility of INRC was evaluated in a small series of stage 4 patients and the designation of response was problematic in a relatively high proportion of cases. The prognostic value of the different responses was highly significant, but less informative than had been hoped for.

Exploiting Symmetry on Parallel Architectures.

NASA Astrophysics Data System (ADS)

Stiller, Lewis Benjamin

1995-01-01

This thesis describes techniques for the design of parallel programs that solve well-structured problems with inherent symmetry. Part I demonstrates the reduction of such problems to generalized matrix multiplication by a group-equivariant matrix. Fast techniques for this multiplication are described, including factorization, orbit decomposition, and Fourier transforms over finite groups. Our algorithms entail interaction between two symmetry groups: one arising at the software level from the problem's symmetry and the other arising at the hardware level from the processors' communication network. Part II illustrates the applicability of our symmetry -exploitation techniques by presenting a series of case studies of the design and implementation of parallel programs. First, a parallel program that solves chess endgames by factorization of an associated dihedral group-equivariant matrix is described. This code runs faster than previous serial programs, and discovered it a number of results. Second, parallel algorithms for Fourier transforms for finite groups are developed, and preliminary parallel implementations for group transforms of dihedral and of symmetric groups are described. Applications in learning, vision, pattern recognition, and statistics are proposed. Third, parallel implementations solving several computational science problems are described, including the direct n-body problem, convolutions arising from molecular biology, and some communication primitives such as broadcast and reduce. Some of our implementations ran orders of magnitude faster than previous techniques, and were used in the investigation of various physical phenomena.

Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial.

PubMed

Fang, Jianqiao; Chen, Lifang; Chen, Luni; Wang, Chao; Keeler, Crystal Lynn; Ma, Ruijie; Xu, Shouyu; Shen, Laihua; Bao, Yehua; Ji, Conghua

2014-12-04

Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture and Chinese herbal medicine. The assessment data will be collected at baseline, 4 and 8 weeks postrandomisation, and then at 12 weeks' follow-up. The primary outcome is measured by the Modified Barthel Index. The secondary outcomes are the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, the mini-mental state examination and Montreal Cognitive, Hamilton's Depression Scale and Self-Rating Depression Scale, and the incidence of adverse events. Ethical approval was obtained from ethics committees of three hospitals. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone, during follow-up calls inquiring on patient's post-study health status. Chinese Clinical Trial Register: ChiCTR-TRC-12001972, http://www.chictr.org/en/proj/show.aspx?proj=2561. 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.

Faecal occult blood testing screening for colorectal cancer and 'missed' interval cancers: are we ignoring the elephant in the room? Results of a multicentre study.

PubMed

George, A T; Aggarwal, S; Dharmavaram, S; Menon, A; Dube, M; Vogler, M; Field, A

2017-05-01

Biennial faecal occult blood testing (FOBT) is used to screen for colorectal cancer throughout the UK. Interval cancers are tumours that develop in patients between screening rounds who have had a negative FOBT. Through a multicentre study, we compared the demographics of patients with interval cancers, FOBT screen detected cancers and cancers that developed in patients who chose not to participate in the screening programme. Five hundred and sixteen colorectal cancers were detected in the screening age group (60-74 years) population in three UK National Health Service hospitals over 2 years. One hundred and twenty seven (25%) were interval cancers, 161 (31%) were screen detected and 228 (44%) were cancers that developed in patients who had declined FOBT. The interval cancer group had a higher incidence of right-sided cancers (38% vs 29% and 24%), a higher proportion of high tumour stages (Dukes C and D) (70% vs 53% and 33%) and a shorter time from diagnosis to death (10 months vs 13 months and 24 months) compared to patients who had declined the FOBT and the FOBT screen detected cancers. Of all the patients studied, those with right-sided interval cancers had the worst outcome. A quarter of the colorectal cancers diagnosed in our study were interval cancers. Patients with right-sided interval cancers had the highest proportion of Dukes C and D tumours coupled with the shortest survival time after diagnosis compared with the other groups. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

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

Effectiveness of two year balance training programme on prevention of fall induced injuries in at risk women aged 75-85 living in community: Ossébo randomised controlled trial.

PubMed

El-Khoury, Fabienne; Cassou, Bernard; Latouche, Aurélien; Aegerter, Philippe; Charles, Marie-Aline; Dargent-Molina, Patricia

2015-07-22

To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75-85 at increased risk of falls and injuries and living in the community. Pragmatic multicentre, two arm, parallel group, randomised controlled trial. 20 study sites in 16 medium to large cities throughout France. 706 women aged 75-85, living in their own home, and with diminished balance and gait capacities, randomly allocated to the experimental intervention group (exercise programme, n=352) or the control group (no intervention, n=354). Weekly supervised group sessions of progressive balance training offered in community based premises for two years, supplemented by individually prescribed home exercises. A geriatrician blinded to group assignment classified falls into one of three categories (no consequence, moderate, severe) based on physical damage and medical care. The primary outcome was the rate of injurious falls (moderate and severe). The two groups were compared for rates of injurious falls with a "shared frailty" model. Other outcomes included the rates of all falls, physical functional capacities (balance and motor function test results), fear of falling (FES-I), physical activity level, and perceived health related quality of life (SF-36). Analysis was by intention to treat. There were 305 injurious falls in the intervention group and 397 in the control group (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). The difference in severe injuries (68 in intervention group v 87 in control group) was of the same order of magnitude (0.83, 0.60 to 1.16). At two years, women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group. Among women who started the intervention (n=294), the median number of group sessions attended was 53 (interquartile range 16-71). Five injurious falls related to the intervention were recorded. A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75-85 at risk of falling.Trial registration ClinicalTrials.gov (NCT00545350). © El-Khoury et al 2015.

Effectiveness of two year balance training programme on prevention of fall induced injuries in at risk women aged 75-85 living in community: Ossébo randomised controlled trial

PubMed Central

El-Khoury, Fabienne; Cassou, Bernard; Latouche, Aurélien; Aegerter, Philippe; Charles, Marie-Aline

2015-01-01

Objective To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75-85 at increased risk of falls and injuries and living in the community. Design Pragmatic multicentre, two arm, parallel group, randomised controlled trial. Setting 20 study sites in 16 medium to large cities throughout France. Participants 706 women aged 75-85, living in their own home, and with diminished balance and gait capacities, randomly allocated to the experimental intervention group (exercise programme, n=352) or the control group (no intervention, n=354). Intervention Weekly supervised group sessions of progressive balance training offered in community based premises for two years, supplemented by individually prescribed home exercises. Outcome measures A geriatrician blinded to group assignment classified falls into one of three categories (no consequence, moderate, severe) based on physical damage and medical care. The primary outcome was the rate of injurious falls (moderate and severe). The two groups were compared for rates of injurious falls with a “shared frailty” model. Other outcomes included the rates of all falls, physical functional capacities (balance and motor function test results), fear of falling (FES-I), physical activity level, and perceived health related quality of life (SF-36). Analysis was by intention to treat. Results There were 305 injurious falls in the intervention group and 397 in the control group (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). The difference in severe injuries (68 in intervention group v 87 in control group) was of the same order of magnitude (0.83, 0.60 to 1.16). At two years, women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group. Among women who started the intervention (n=294), the median number of group sessions attended was 53 (interquartile range 16-71). Five injurious falls related to the intervention were recorded. Conclusion A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75-85 at risk of falling. Trial registration ClinicalTrials.gov (NCT00545350). PMID:26201510

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.

Efficacy and safety of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus uncontrolled on metformin monotherapy: Results of a Phase IV open-label randomized controlled study (the SMART study).

PubMed

Du, Jin; Liang, Li; Fang, Hui; Xu, Fengmei; Li, Wei; Shen, Liya; Wang, Xueying; Xu, Chun; Bian, Fang; Mu, Yiming

2017-11-01

To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. SMART was a 24-week, multicentre, randomized, parallel-group, open-label Phase IV study conducted at 35 sites in China (September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events (GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication. Four-hundred and eighty-eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre- and ≥1 post-baseline efficacy values recorded. Saxagliptin was non-inferior to acarbose for glycaemic control [Week 24 HbA1c change: -0.82% and -0.78%, respectively; difference (95% confidence interval): -0.04 (-0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose. Both therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice. NCT02243176, clinicaltrials.gov. © 2017 John Wiley & Sons Ltd.

A multicentre randomised controlled trial to evaluate the efficacy, morbidity and functional outcome of endoscopic transanal proctectomy versus laparoscopic proctectomy for low-lying rectal cancer (ETAP-GRECCAR 11 TRIAL): rationale and design.

PubMed

Lelong, Bernard; de Chaisemartin, Cécile; Meillat, Helene; Cournier, Sandra; Boher, Jean Marie; Genre, Dominique; Karoui, Mehdi; Tuech, Jean Jacques; Delpero, Jean Robert

2017-04-11

Total mesorectal excision is the standard surgical treatment for mid- and low-rectal cancer. Laparoscopy represents a clear leap forward in the management of rectal cancer patients, offering significant improvements in post-operative measures such as pain, first bowel movement, and hospital length of stay. However, there are still some limits to its applications, especially in difficult cases. Such cases may entail either conversion to an open procedure or positive resection margins. Transanal endoscopic proctectomy (ETAP) was recently described and could address the difficulties of approaching the lower third of the rectum. Early series and case-control studies have shown favourable short-term results, such as a low conversion rate, reduced hospital length of stay and oncological outcomes comparable to laparoscopic surgery. The aim of the proposed study is to compare the rate of positive resection margins (R1 resection) with ETAP versus laparoscopic proctectomy (LAP), with patients randomly assigned to each arm. The proposed study is a multicentre randomised trial using two parallel groups to compare ETAP and LAP. Patients with T3 lower-third rectal adenocarcinomas for whom conservative surgery with manual coloanal anastomosis is planned will be recruited. Randomisation will be performed immediately prior to surgery after ensuring that the patient meets the inclusion criteria and completing the baseline functional and quality of life tests. The study is designed as a non-inferiority trial with a main criterion of R0/R1 resection. Secondary endpoints will include the conversion rate, the minimal invasiveness of the abdominal approach, postoperative morbidity, the length of hospital stay, mesorectal macroscopic assessment, functional urologic and sexual results, faecal continence, global quality of life, stoma-free survival, and disease-free survival at 3 years. The inclusion period will be 3 years, and every patient will be followed for 3 years. The number of patients needed is 226. There is a strong need for optimal evaluation of the ETAP because of substancial changes in the operative technique. Assessment of oncological safety and septic risk, as well as digestive and urological functional results, is particularily mandatory. Moreover, benefits of the ETAP technique could be demonstrated  in post-operative outcome. ClinicalTrial.gov: NCT02584985 . Date and version identifier: Version n°2 - 2015 July 6.

Dose escalation study to evaluate safety, tolerability and efficacy of intravenous etoposide phosphate administration in 27 dogs with multicentric lymphoma

PubMed Central

Hordeaux, Juliette; Bouchaert, Emmanuel; Gomes, Bruno

2017-01-01

Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies. This work was part of a comparative oncology project assessing a new, clinical-stage topoisomerase II inhibitor and comparing it with etoposide in dogs with spontaneous lymphoma with the objective to translate findings from dogs to humans. Etoposide is a topoisomerase II inhibitor widely used in various humans’ solid and hematopoietic cancer, but little data is available concerning its potential antitumor efficacy in dogs. Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous etoposide phosphate in dogs with multicentric lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric lymphoma were enrolled and treated with three cycles of etoposide phosphate IV injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no hypersensitivity reaction were reported at this dose level. Beyond the characterization of etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human lymphomas. PMID:28505195

Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study.

PubMed

Ebner, Thomas; Montag, Markus; Montag, M; Van der Ven, K; Van der Ven, H; Ebner, T; Shebl, O; Oppelt, P; Hirchenhain, J; Krüssel, J; Maxrath, B; Gnoth, C; Friol, K; Tigges, J; Wünsch, E; Luckhaus, J; Beerkotte, A; Weiss, D; Grunwald, K; Struller, D; Etien, C

2015-04-01

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles (P < 0.001). Further splitting of the historical control group into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed that all groups significantly benefitted (P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Randomised controlled study in the primary healthcare sector to investigate the effectiveness and safety of auriculotherapy for the treatment of uncomplicated chronic rachialgia: a study protocol.

PubMed

Vas, Jorge; Aguilar, Inmaculada; Campos, M Angeles; Méndez, Camila; Perea-Milla, Emilio; Modesto, Manuela; Caro, Paloma; Martos, Francisco; García-Ruiz, Antonio J

2008-07-06

Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course. The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis. This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia. Current Controlled Trials ISRCTN01897462.

Randomised controlled study in the primary healthcare sector to investigate the effectiveness and safety of auriculotherapy for the treatment of uncomplicated chronic rachialgia: a study protocol

PubMed Central

Vas, Jorge; Aguilar, Inmaculada; Campos, M Ángeles; Méndez, Camila; Perea-Milla, Emilio; Modesto, Manuela; Caro, Paloma; Martos, Francisco; García-Ruiz, Antonio J

2008-01-01

Background Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course. Methods/Design The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis. Discussion This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia. Trial registration Current Controlled Trials ISRCTN01897462. PMID:18601750

Long-term safety and efficacy of tofogliflozin as add-on to insulin in patients with type 2 diabetes: Results from a 52-week, multicentre, randomized, double-blind, open-label extension, Phase 4 study in Japan (J-STEP/INS).

PubMed

Terauchi, Yasuo; Tamura, Masahiro; Senda, Masayuki; Gunji, Ryoji; Kaku, Kohei

2018-05-01

To evaluate the long-term safety and efficacy of tofogliflozin as an add-on treatment to insulin over 52 weeks. This 52-week, multicentre, Phase 4 study consisted of a 16-week, randomized, double-blind, placebo-controlled phase and a 36-week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%-10.5%) receiving insulin monotherapy (basal-bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase-4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the 'tofo-tofo group' and patients who received placebo and tofogliflozin (36 weeks) were referred to as the 'pla-tofo group'. A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment-emergent adverse event (AE) (42.9% in the tofo-tofo group and 29.4% in the pla-tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo-tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla-tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo-tofo and pla-tofo groups were 8.53% (-0.76% ± 0.077) and 8.40% (-0.73% ± 0.102); 68.84 kg (-1.52 kg ± 0.207) and 72.24 kg (-2.13 kg ± 0.313), respectively. This study demonstrates the safety and efficacy of tofogliflozin as add-on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

PubMed

Shaw, E; Miró, J M; Puig-Asensio, M; Pigrau, C; Barcenilla, F; Murillas, J; Garcia-Pardo, G; Espejo, E; Padilla, B; Garcia-Reyne, A; Pasquau, J; Rodriguez-Baño, J; López-Contreras, J; Montero, M; de la Calle, C; Pintado, V; Calbo, E; Gasch, O; Montejo, M; Salavert, M; Garcia-Pais, M J; Carratalà, J; Pujol, M

2015-03-11

Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. NCT01898338. 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.

The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial.

PubMed

White, David; Waugh, Norman; Elliott, Jackie; Lawton, Julia; Barnard, Katharine; Campbell, Michael J; Dixon, Simon; Heller, Simon

2014-09-03

People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education. A multicentre, parallel group, cluster randomised controlled trial among 280 adults with T1DM. All participants attended the week-long dose adjustment for normal eating (DAFNE) structured education course, and receive either multiple daily injections or pump therapy for 2 years. The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis. The primary outcome will be the change in glycosylated haemoglobin (HbA1c) at 24 months in those participants whose baseline HbA1c is at or above 7.5% (58 mmol/mol). The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5% (58 mmol/mol) or less at 24 months. The protocol was approved by the Research Ethics Committee North West, Liverpool East and received Medicines and Healthcare products Regulatory Agency (MHRA) clinical trials authorisation. Each participating centre gave National Health Service R&D approval. We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations, including lay user groups. ISRCTN 61215213. 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.

Parent-Child Parallel-Group Intervention for Childhood Aggression in Hong Kong

ERIC Educational Resources Information Center

Fung, Annis L. C.; Tsang, Sandra H. K. M.

2006-01-01

This article reports the original evidence-based outcome study on parent-child parallel group-designed Anger Coping Training (ACT) program for children aged 8-10 with reactive aggression and their parents in Hong Kong. This research program involved experimental and control groups with pre- and post-comparison. Quantitative data collection…

Reference intervals: current status, recent developments and future considerations.

PubMed

Ozarda, Yesim

2016-01-01

Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term 'RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area. 
The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs.

Reference intervals: current status, recent developments and future considerations

PubMed Central

Ozarda, Yesim

2016-01-01

Reliable and accurate reference intervals (RIs) for laboratory analyses are an integral part of the process of correct interpretation of clinical laboratory test results. RIs given in laboratory reports have an important role in aiding the clinician in interpreting test results in reference to values for healthy populations. Since the 1980s, the International Federation of Clinical Chemistry (IFCC) has been proactive in establishing recommendations to clarify the true significance of the term ‘RIs, to select the appropriate reference population and statistically analyse the data. The C28-A3 guideline published by the Clinical and Laboratory Standards Institute (CLSI) and IFCC is still the most widely-used source of reference in this area. In recent years, protocols additional to the Guideline have been published by the IFCC, Committee on Reference Intervals and Decision Limits (C-RIDL), including all details of multicenter studies on RIs to meet the requirements in this area. Multicentric RIs studies are the most important development in the area of RIs. Recently, the C-RIDL has performed many multicentric studies to obtain common RIs. Confusion of RIs and clinical decision limits (CDLs) remains an issue and pediatric and geriatric age groups are a significant problem. For future studies of RIs, the genetic effect would seem to be the most challenging area.
The aim of the review is to present the current theory and practice of RIs, with special emphasis given to multicenter RIs studies, RIs studies for pediatric and geriatric age groups, clinical decision limits and partitioning by genetic effects on RIs. PMID:26981015

Randomized controlled trial of an intervention to improve drug appropriateness in community-dwelling polymedicated elderly people.

PubMed

Campins, Lluís; Serra-Prat, Mateu; Gózalo, Inés; López, David; Palomera, Elisabet; Agustí, Clara; Cabré, Mateu

2017-02-01

Polypharmacy is frequent in the elderly population and is associated with potentially drug inappropriateness and drug-related problems. To assess the effectiveness and safety of a medication evaluation programme for community-dwelling polymedicated elderly people. Randomized, open-label, multicentre, parallel-arm clinical trial with 1-year follow-up. Primary care centres. Polymedicated (≥8 drugs) elderly people (≥70 years). Pharmacist review of all medication according to the Good Palliative-Geriatric Practice algorithm and the Screening Tool of Older Person's Prescriptions-Screening Tool to Alert Doctors to the Right Treatment criteria and recommendations to the patient's physician. Routine clinical practice. Recommendations and changes implemented, number of prescribed drugs, restarted drugs, primary care and emergency department consultations, hospitalizations and death. About 503 (252 intervention and 251 control) patients were recruited and 2709 drugs were evaluated. About 26.5% of prescriptions were rated as potentially inappropriate and 21.5% were changed (9.1% discontinuation, 6.9% dose adjustment, 3.2% substitution and 2.2% new prescription). About 2.62 recommendations per patient were made and at least one recommendation was made for 95.6% of patients. The mean number of prescriptions per patient was significantly lower in the intervention group at 3- and 6-month follow-up. Discontinuations, dose adjustments and substitutions were significantly higher than in the control group at 3, 6 and 12 months. No differences were observed in the number of emergency visits, hospitalizations and deaths. The study intervention was safe, reduced potentially inappropriate medication, but did not reduce emergency visits and hospitalizations in polymedicated elderly people. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Bridging the age gap in breast cancer: evaluation of decision support interventions for older women with operable breast cancer: protocol for a cluster randomised controlled trial.

PubMed

Collins, Karen; Reed, Malcolm; Lifford, Kate; Burton, Maria; Edwards, Adrian; Ring, Alistair; Brain, Katherine; Harder, Helena; Robinson, Thompson; Cheung, Kwok Leung; Morgan, Jenna; Audisio, Riccardo; Ward, Susan; Richards, Paul; Martin, Charlene; Chater, Tim; Pemberton, Kirsty; Nettleship, Anthony; Murray, Christopher; Walters, Stephen; Bortolami, Oscar; Armitage, Fiona; Leonard, Robert; Gath, Jacqui; Revell, Deirdre; Green, Tracy; Wyld, Lynda

2017-07-31

While breast cancer outcomes are improving steadily in younger women due to advances in screening and improved therapies, there has been little change in outcomes among the older age group. It is inevitable that comorbidities/frailty rates are higher, which may increase the risks of some breast cancer treatments such as surgery and chemotherapy, many older women are healthy and may benefit from their use. Adjusting treatment regimens appropriately for age/comorbidity/frailty is variable and largely non-evidence based, specifically with regard to rates of surgery for operable oestrogen receptor-positive disease and rates of chemotherapy for high-risk disease. This multicentre, parallel group, pragmatic cluster randomised controlled trial (RCT) (2015-18) reported here is nested within a larger ongoing 'Age Gap Cohort Study' (2012-18RP-PG-1209-10071), aims to evaluate the effectiveness of a complex intervention of decision support interventions to assist in the treatment decision making for early breast cancer in older women. The interventions include two patient decision aids (primary endocrine therapy vs surgery/antioestrogen therapy and chemotherapy vs no chemotherapy) and a clinical treatment outcomes algorithm for clinicians. National and local ethics committee approval was obtained for all UK participating sites. Results from the trial will be submitted for publication in international peer-reviewed scientific journals. 115550. European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2015-004220-61;Pre-results. Sponsor's Protocol Code Number Sheffield Teaching Hospitals STH17086. ISRCTN 32447*. © 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 Multi-centric, Double-blind, Placebo-controlled, Randomized, Prospective Study to Evaluate the Efficacy and Safety of Carica papaya Leaf Extract, as Empirical Therapy for Thrombocytopenia associated with Dengue Fever.

PubMed

Kasture, Prabhu Nagnathappa; Nagabhushan, K H; Kumar, Arun

2016-06-01

Dengue is a rapidly expanding global health problem. Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. The management of dengue virus infection is essentially supportive and symptomatic and no specific treatment is available for increasing the fallen platelets, which have a significant role in causing the mortality of dengue patient.This study was conducted to evaluate the platelet increasing efficacy of Carica papaya leaf extract (CPLE) in patients with dengue fever (DF). The administration of Carica papaya leaf extract should significantly increase the platelet count in cases of thrombocytopenia associated with dengue, preventing the patient to go in DHF or DSS conditions. A Multi-centric, Double blind, Placebo controlled, Randomized, prospective study was conducted in 300 patients across 5 centres', to evaluate the Efficacy and Safety of Carica Papaya Leaf Extract, as empirical therapy for thrombocytopenia associated with dengue fever. The subjects were randomized into two groups, as control and intervention group. Both the groups were managed by the standard management guidelines for dengue except steroid administration. In addition to this, the intervention group received CPLE tablet three times daily for five days. All of them were followed daily with platelet monitoring. This study has been registered in the clinical trial registry-India (CTRI Registration number: CTRI/2015/05/005806). The results indicate that CPLE had significant increase(p< 0.01) in the platelet count over the therapy duration, in dengue fever patients, confirming CPLE accelerates the increase in platelet count compared to the control group. There were few adverse events related to GI disturbance like nausea and vomiting which were similar in both groups. Thus this study concluded that Carica papaya leaf extract (CPLE) does significantly increase the platelet count in patients with thrombocytopenia associated with dengue with fewer side effects and good tolerability.

A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years.

PubMed

Kon, Elizaveta; Filardo, Giuseppe; Brittberg, Mats; Busacca, Maurizio; Condello, Vincenzo; Engebretsen, Lars; Marlovits, Stefan; Niemeyer, Philipp; Platzer, Patrik; Posthumus, Michael; Verdonk, Peter; Verdonk, Renè; Victor, Jan; van der Merwe, Willem; Widuchowski, Wojciech; Zorzi, Claudio; Marcacci, Maurilio

2017-09-14

The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions. I.

[Combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome: a multi-central randomized controlled trial].

PubMed

Jang, Zhen-Ya; Li, Chang-Du; Qiu, Ling; Guo, Jun-Hua; He, Ling-Na; Yue, Yang; Li, Fang-Ze; Qin, Wen-Yi

2010-04-01

To evaluate the clinical effect of combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome. By using multi-central randomized controlled method, 186 cases were randomly divided into an acupuncture combined with cupping and western medicine group (group A), an acupuncture combined with cupping group (group B) and a western medicine group (group C) and treated continuously for 4 weeks. The treatment of acupuncture combined with cupping was produced by acupuncture at five mental points and moving cupping on the Hechelu of the back, once evrey other day, thrice each week, and the western medicine therapy by oral administration of Amitriptyline, once each day. The scores of McGill Pain Questionnaire (MPQ), the amount of tenderness point and the time of producing effect were compared and the therapeutic effects were assessed with the Hamilton Depression Scale (HAMD). The cured and markedly effective rate was 65.0% (39/60) in the group A, which was superior to 15.9% (10/63) in the group B and 16.1% (9/56) in the group C (both P < 0.001). After treatment, the scores of MPQ and HAMD and the amount of tenderness point all decreased in the three groups, group A being significantly better than group B and group C, and the time of producing effect in the group A was more earlier than those in the group B and the group C. The therapeutic effect of combination of acupuncture, cupping and medicine on fibromyalgia syndrome is superior to that of the simple acupuncture combined with cupping or the simple medicine.

[Local approval procedures act as a brake on RCTs].

PubMed

van der Stok, E P; Huiskens, J; Hemmes, B; Grünhagen, D J; van Gulik, T M; Verhoef, C; Punt, C J A

2016-01-01

Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. Retrospective, descriptive. All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from € 0-€ 1750, and amounted to € 8575 for all procedures combined. No costs were charged by the majority of the centres. The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context.

The specificity of learned parallelism in dual-memory retrieval.

PubMed

Strobach, Tilo; Schubert, Torsten; Pashler, Harold; Rickard, Timothy

2014-05-01

Retrieval of two responses from one visually presented cue occurs sequentially at the outset of dual-retrieval practice. Exclusively for subjects who adopt a mode of grouping (i.e., synchronizing) their response execution, however, reaction times after dual-retrieval practice indicate a shift to learned retrieval parallelism (e.g., Nino & Rickard, in Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 373-388, 2003). In the present study, we investigated how this learned parallelism is achieved and why it appears to occur only for subjects who group their responses. Two main accounts were considered: a task-level versus a cue-level account. The task-level account assumes that learned retrieval parallelism occurs at the level of the task as a whole and is not limited to practiced cues. Grouping response execution may thus promote a general shift to parallel retrieval following practice. The cue-level account states that learned retrieval parallelism is specific to practiced cues. This type of parallelism may result from cue-specific response chunking that occurs uniquely as a consequence of grouped response execution. The results of two experiments favored the second account and were best interpreted in terms of a structural bottleneck model.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].

PubMed

Al-Chalabi, Ammar; Shaw, Pamela J; Young, Carolyn A; Morrison, Karen E; Murphy, Caroline; Thornhill, Marie; Kelly, Joanna; Steen, I Nicholas; Leigh, P Nigel

2011-09-21

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Current controlled trials ISRCTN83178718.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease.

PubMed

Lawlor, Brian; Kennelly, Sean; O'Dwyer, Sarah; Cregg, Fiona; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Howard, Robert; Murphy, Caroline; Adams, Jessica; Daly, Leslie; Segurado, Ricardo; Gaynor, Siobhan; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Wallin, Anders; Borjesson, Anne; Molloy, William; Tsolaki, Magda; Olde Rikkert, Marcel

2014-10-09

This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. EUDRACT Reference Number: 2012-002764-27. 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.

Exploring threats to generalisability in a large international rehabilitation trial (AVERT).

PubMed

Bernhardt, Julie; Raffelt, Audrey; Churilov, Leonid; Lindley, Richard I; Speare, Sally; Ancliffe, Jacqueline; Katijjahbe, Md Ali; Hameed, Shahul; Lennon, Sheila; McRae, Anna; Tan, Dawn; Quiney, Jan; Williamson, Hannah C; Collier, Janice; Dewey, Helen M; Donnan, Geoffrey A; Langhorne, Peter; Thrift, Amanda G

2015-08-17

The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Acute stroke units at 44 hospitals in 8 countries. The first 20,000 patients screened for AVERT, of whom 1158 were recruited and randomised. We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). 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.

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care.

PubMed

Kai, Joe; Middleton, Lee; Daniels, Jane; Pattison, Helen; Tryposkiadis, Konstantinos; Gupta, Janesh

2016-12-01

Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. In total, 571 women aged 25-50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen-progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = -0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery. © British Journal of General Practice 2016.

Recurrence rates and patient assessed outcomes of 0.5% 5-fluorouracil in combination with salicylic acid treating actinic keratoses.

PubMed

Stockfleth, Eggert; Zwingers, Thomas; Willers, Christoph

2012-01-01

Actinic keratoses (AK) have been classified as early in situ squamous cell carcinomas and should be treated. To evaluate the clinical benefit of 5-fluorouracil 0.5%/salicylic acid 10.0% (5-FU/SA) versus 3% diclofenac/hyaluronic acid (HA) for the treatment of AK and report patients' assessments of efficacy, tolerability and practicability. Randomised, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical 0.5% 5-FU/SA once daily, its vehicle or diclofenac/HA twice daily for maximum of 12 weeks. Lesion recurrence rates were evaluated at 6 and 12 months after end of treatment (EOT). Patients' assessments were evaluated at 6 weeks, EOT, post-treatment (PT) visit, 6 and 12 months. At 12 months 85.8% of lesions did not recur in the 5-FU/SA group compared to 79.8% (p=0.04419) in the vehicle and 81.0% (p=0.02476) in the diclofenac/HA groups. At PT visit 93.2% patients (n=163/175) in the 5-FU/SA group rated clinical improvement as "very good" or "good" compared to vehicle (66.7%, n=62/93, p<0.0001) and diclofenac/HA (81.6%, n=142/174, p<0.0001). Local side effects (inflammation and burning) were more common with 0.5% FU/SA but in general did not lead to discontinuation of therapy. Overall, patients were satisfied with the therapy. At 12 months, there were no differences in practicability and handling between treatments. Topical 0.5% 5-FU/SA demonstrated superior sustained clinical efficacy versus diclofenac/HA with acceptable tolerability. Patient satisfaction was high.

Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study.

PubMed

Wallace, Daniel J; Kalunian, Kenneth; Petri, Michelle A; Strand, Vibeke; Houssiau, Frederic A; Pike, Marilyn; Kilgallen, Brian; Bongardt, Sabine; Barry, Anna; Kelley, Lexy; Gordon, Caroline

2014-01-01

To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37-39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing.

Simulation-based team training for multi-professional obstetric care teams to improve patient outcome: a multicentre, cluster randomised controlled trial.

PubMed

Fransen, A F; van de Ven, J; Schuit, E; van Tetering, Aac; Mol, B W; Oei, S G

2017-03-01

To investigate whether simulation-based obstetric team training in a simulation centre improves patient outcome. Multicentre, open, cluster randomised controlled trial. Obstetric units in the Netherlands. Women with a singleton pregnancy beyond 24 weeks of gestation. Random allocation of obstetric units to a 1-day, multi-professional, simulation-based team training focusing on crew resource management (CRM) in a simulation centre or to no such team training. Intention-to-treat analyses were performed at the cluster level, including a measurement 1 year prior to the intervention. Primary outcome was a composite outcome of obstetric complications during the first year post-intervention, including low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischaemic encephalopathy. Maternal and perinatal mortality were also registered. Each study group included 12 units with a median unit size of 1224 women, combining for a total of 28 657 women. In total, 471 medical professionals received the training course. The composite outcome of obstetric complications did not differ between study groups [odds ratio (OR) 1.0, 95% confidence interval (CI) 0.80-1.3]. Team training reduced trauma due to shoulder dystocia (OR 0.50, 95% CI 0.25-0.99) and increased invasive treatment for severe postpartum haemorrhage (OR 2.2, 95% CI 1.2-3.9) compared with no intervention. Other outcomes did not differ between study groups. A 1-day, off-site, simulation-based team training, focusing on teamwork skills, did not reduce a composite of obstetric complications. 1-day, off-site, simulation-based team training did not reduce a composite of obstetric complications. © 2016 Royal College of Obstetricians and Gynaecologists.

Risk-adapted approach for fever and neutropenia in paediatric cancer patients--a national multicentre study.

PubMed

Miedema, Karin G E; Tissing, Wim J E; Abbink, Floor C H; Ball, Lynne M; Michiels, Erna M C; van Vliet, Michel J; de Vries, Wilma Y; Kamps, Willem A; Norbruis, Obbe F; Fiocco, Marta; de Groot-Kruseman, Hester A; van de Wetering, Marianne D; de Bont, Eveline S J M

2016-01-01

In this national multicentre study, we examined the safety of reducing antibiotics in selected paediatric cancer patients with febrile neutropenia. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk and received antibiotic therapy. Remaining patients were allocated to low- or medium risk, depending on their interleukin-8 level. Low-risk patients did not receive any antibiotics and were discharged from the hospital after having been afebrile for 12 h. Medium-risk patients were re-evaluated after 72 h of antibiotic treatment and, in selected patients, antibiotics were stopped. Two hundred thirty-three febrile neutropenic episodes in 141 paediatric cancer patients were included in the study. Sixty-four episodes were classified high risk (28%), 122 medium risk (52%), and 47 (20%) low risk. In the medium-risk group, antibiotics were stopped after 72 h in 50 in 122 episodes (41%). Median duration of antibiotic treatment and hospital admission was significantly lower in low- and medium-risk episodes with early discharge. No failures were observed in the medium-risk group with early discharge. In the low-risk group, six failures were observed (12.8%), due to coagulase-negative staphylococci-positive blood cultures and recurrent fever. We showed that it is safe to shorten antibiotic treatment to 72 h in selected medium-risk patients with febrile neutropenia, regardless of the neutrophil count. The safety of withholding antibiotics in selected low-risk paediatric cancer patients with febrile neutropenia requires further investigation, using more suitable definitions for safety. Reduction in hospital admissions allows children with cancer more time at home and consequently improves their quality of life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measurement of HbA1c in multicentre diabetes trials - should blood samples be tested locally or sent to a central laboratory: an agreement analysis.

PubMed

Arch, Barbara N; Blair, Joanne; McKay, Andrew; Gregory, John W; Newland, Paul; Gamble, Carrol

2016-10-24

Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For multicentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a central laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up data collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes. HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and 12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of agreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of error between measurements was subjectively set as ±10 % for HbA1c. The percentage of pairs of measurements that were classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within centres. Treatment group was not considered. Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four follow-up time points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD = 4.5, 95 % CI -0.2 to 0.5) higher than central. The 95 % limits of agreement were -8.6 to 9.0 mmol/mol (local minus central). Eighty percent of local measurements were within ±10 % of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias. Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected and standard deviations were similar. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements. We recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting. Eudract No. 2010-023792-25 , registered on 4 November 2010.

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.

The effect of prandial glucose regulation with repaglinide on treatment satisfaction, wellbeing and health status in patients with pharmacotherapy naïve Type 2 diabetes: a placebo-controlled, multicentre study.

PubMed

Bech, Per; Moses, Robert; Gomis, Ramón

2003-06-01

This prospective, 16-week, randomised, double-blind, parallel-group study assessed the differential impact of the prandial glucose regulating oral hypoglycaemic drug, repaglinide, and placebo upon perceptions of quality of life (QoL) and treatment satisfaction in pharmacotherapy-naive patients with Type 2 diabetes. In addition, the study assessed whether these outcomes were influenced by the patients' level of glycaemic control. A total of 253 patients were randomised in a 2:1 ratio of repaglinide: placebo, with doses taken flexibly with main meals (2-4 per day), whenever they were eaten. Repaglinide was initiated at 0.5 mg per meal, increased to 1 mg after 4 weeks if fasting plasma glucose exceeded 7.8 mmol/l. QoL and treatment satisfaction outcomes were compared using generic and disease-specific self-assessment measures, previously applied in diabetes: the WHO Wellbeing Questionnaire (WHO-WBQ), WHO Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ) and EuroQoL EQ-5D. Over the trial period, repaglinide-treated patients reported a significant 9% improvement in (WHO-DTSQ) treatment satisfaction score (p < 0.05). No significant increase was associated with placebo. The correlation between decrease in glycated haemoglobin (HbA1c) and increase in treatment satisfaction (WHO-DTSQ) was -0.22 (p < 0.01). Scores obtained with the other measures did not change significantly during the trial in either group, but the cohort exhibited only a slight reduction in wellbeing (WHO-WBQ) and health status (EQ-5D) at baseline compared with the background population. In conclusion, flexible mealtime dosing with oral medication appears to be well accepted by pharmacotherapy-naïve patients with Type 2 diabetes. The results suggest that repaglinide provides a higher level of treatment satisfaction than placebo, and this may in part relate to improved glycaemic control.

Randomised controlled trial of a 12 week yoga intervention on negative affective states, cardiovascular and cognitive function in post-cardiac rehabilitation patients.

PubMed

Yeung, Alan; Kiat, Hosen; Denniss, A Robert; Cheema, Birinder S; Bensoussan, Alan; Machliss, Bianca; Colagiuri, Ben; Chang, Dennis

2014-10-24

Negative affective states such as anxiety, depression and stress are significant risk factors for cardiovascular disease, particularly in cardiac and post-cardiac rehabilitation populations.Yoga is a balanced practice of physical exercise, breathing control and meditation that can reduce psychosocial symptoms as well as improve cardiovascular and cognitive function. It has the potential to positively affect multiple disease pathways and may prove to be a practical adjunct to cardiac rehabilitation in further reducing cardiac risk factors as well as improving self-efficacy and post-cardiac rehabilitation adherence to healthy lifestyle behaviours. This is a parallel arm, multi-centre, randomised controlled trial that will assess the outcomes of post- phase 2 cardiac rehabilitation patients assigned to a yoga intervention in comparison to a no-treatment wait-list control group. Participants randomised to the yoga group will engage in a 12 week yoga program comprising of two group based sessions and one self-administered home session each week. Group based sessions will be led by an experienced yoga instructor. This will involve teaching beginner students a hatha yoga sequence that incorporates asana (poses and postures), pranayama (breathing control) and meditation. The primary outcomes of this study are negative affective states of anxiety, depression and stress assessed using the Depression Anxiety Stress Scale. Secondary outcomes include measures of quality of life, and cardiovascular and cognitive function. The cardiovascular outcomes will include blood pressure, heart rate, heart rate variability, pulse wave velocity, carotid intima media thickness measurements, lipid/glucose profiles and C-reactive protein assays. Assessments will be conducted prior to (week 0), mid-way through (week 6) and following the intervention period (week 12) as well as at a four week follow-up (week 16). This study will determine the effect of yoga practice on negative affective states, cardiovascular and cognitive function in post-phase 2 cardiac rehabilitation patients. The findings may provide evidence to incorporate yoga into standardised cardiac rehabilitation programs as a practical adjunct to improve the management of psychosocial symptoms associated with cardiovascular events in addition to improving patients' cognitive and cardiovascular functions. ACTRN12612000358842.

Multicentric GISCoR Study "intensive clinical follow-up versus surgical radicalization after complete endoscopic polypectomy of a malignant adenoma" (SEC-GISCoR).

PubMed

Andreoni, Bruno; Camellini, Lorenzo; Sonzogni, Angelica; Crosta, Cristiano; Pirola, Maria Elena; Corbellini, Carlo

2011-09-01

Colorectal cancer screening programs result in an early diagnosis of the disease. In 2007, 250 malignant polyps were identified in Lombardy, out of 1,329 screen-detected colorectal carcinomas. The Italian Group for Colorectal Cancer (GISCoR) promoted the multicentric study "Endoscopic Follow-up versus Surgical Radicalization of Malignant Polyps after Complete Endoscopic Polypectomy" (SEC-GISCoR). The protocol was a multicentric, prospective, observational, non-randomized study. It included patients diagnosed a colorectal malignant adenoma, after complete endoscopic removal. From November 2005 to September 2009, three participating centers enrolled 120 patients with malignant polyps after "complete" endoscopic polypectomy; malignant polyps were classified as "low risk" or "high risk". The study had two arms: "Intensive follow-up" (42 patients: 32 with low-risk and 10 with high-risk polyps) and "Surgical radicalization" (78 patients: 5 with low-risk and 73 with high-risk polyps). Data were collected using an online CRF. Overall, 37/120 polyps (30.8%) were low risk and 83/120 (69.2%) were high risk. 42 out of 120 patients (35%) were enrolled in the "clinical follow-up" arm, while 78/120 (65%) entered the surgery arm. In 15 cases, patients were not enrolled in the correct arm, according to the criteria agreed upon before starting the study. There still is a high incidence (11.5%) of pathological mismatches. No clinical event was reported in 2.9 years of follow-up. In conclusion, some differences emerged in the management of patients with malignant polyps among participating centers (p < 0.001), mismatches can be explained by high surgical risk or patient's choice. Only in 5 cases (4.2%), did data analysis not allow to exactly determine the reason for a choice different from protocol criteria. The availability of new risk factors and the evidence of pathological mismatches confirmed the need for future studies on this issue.

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

PubMed Central

Vallance, Abigail E; Young, Alastair L; Macutkiewicz, Christian; Roberts, Keith J; Smith, Andrew M

2015-01-01

Background A post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality. Method An electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool. Results Six eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50). Conclusion These scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed. PMID:26456948

Posterior chamber phakic intraocular lens implantation: comparative, multicentre study in 351 eyes with low-to-moderate or high myopia.

PubMed

Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kitazawa, Yoshihiro; Kojima, Takashi; Nakamura, Tomoaki; Oka, Yoshitaka; Matsumoto, Rei

2018-02-01

To compare the clinical outcomes of posterior chamber phakic intraocular lens implantation with a central hole (Hole Implantable Collamer Lens (ICL), STAAR Surgical) for low-to-moderate myopia and for high myopia. This multicentre retrospective case series comprised 351 eyes of 351 consecutive patients undergoing ICL implantation. Eyes were divided into groups based on preoperative degree of myopia: group 1; 57 eyes, manifest spherical equivalent less than -6 dioptres (D), and group 2; 294 eyes, -6 D or more. Safety, efficacy, predictability, stability and adverse events were compared preoperatively; and at 1 day, 1 week and 1, 3, 6 and 12 months postoperatively, RESULTS: Uncorrected and corrected visual acuities were -0.17±0.14 and -0.21±0.10 logMAR in group 1, and -0.16±0.09 and -0.21±0.08 logMAR in group 2, 1 year postoperatively. In groups 1 and 2, 98% and 99% of eyes were within 1.0 D of the targeted correction. Manifest refraction changes of -0.12±0.34 D (group 1) and -0.18±0.43 D (group 2) occurred from 1 day to 1 year. ICL exchanges were necessary in two eyes (0.7%) in group 2. No vision-threatening complications occurred at any time. The ICL performed well for the correction of both low-to-moderate myopia and high myopia throughout the 1-year observation period. The clinical outcomes of ICL implantation for low-to-moderate myopia are essentially equivalent to those for high myopia. © 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.

Influence of de qi on the immediate analgesic effect of SP6 acupuncture in patients with primary dysmenorrhoea and cold and dampness stagnation: a multicentre randomised controlled trial.

PubMed

Zhao, Min-Yi; Zhang, Peng; Li, Jing; Wang, Lin-Peng; Zhou, Wei; Wang, Yan-Xia; She, Yan-Fen; Ma, Liang-Xiao; Wang, Pei; Hu, Ni-Juan; Lin, Chi; Hu, Shang-Qin; Wu, Gui-Wen; Wang, Ya-Feng; Sun, Jun-Jun; Jiang, Si-Zhu; Zhu, Jiang

2017-10-01

The aim of this multicentre randomised controlled trial was to investigate the contribution of de qi to the immediate analgesic effect of acupuncture in patients with primary dysmenorrhoea and the specific traditional Chinese medicine diagnosis cold and dampness stagnation . Eighty-eight patients with primary dysmenorrhoea and cold and dampness stagnation were randomly assigned to de qi (n=43) or no de qi (n=45) groups and underwent 30 min of SP6 acupuncture. The de qi group received deep needling at SP6 with manipulation using thick needles; the no de qi group received shallow needling with no manipulation using thin needles. In both groups the pain scores and actual de qi sensation were evaluated using a visual analogue scale for pain (VAS-P) and the acupuncture de qi clinical assessment scale (ADCAS), respectively. Both groups showed reductions in VAS-P, with no signficant differences between groups. ADCAS scores showed 43/43 and 25/45 patients in de qi and no de qi groups, respectively, actually experienced de qi sensation. Independent of original group allocation, VAS-P reductions associated with actual de qi (n=68) were greater than those without (28.4±18.19 mm vs 14.6±12.28 mm, p=0.008). This study showed no significant difference in VAS-P scores in patients with primary dysmenorrhoea and cold and dampness stagnation immediately after SP6 acupuncture designed to induce or avoid de qi sensation. Both treatments significantly reduced VAS-P relative to baseline. Irrespective of group allocation, patients experiencing actual de qi sensation demonstrated larger reductions in pain score relative to those without, suggesting greater analgesic effects. Chinese Clinical Trial Registry (ChiCTR-TRC-13003086); 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.

Mitral valve surgery in emergency for severe acute regurgitation: analysis of postoperative results from a multicentre study.

PubMed

Lorusso, Roberto; Gelsomino, Sandro; De Cicco, Giuseppe; Beghi, Cesare; Russo, Claudio; De Bonis, Michele; Colli, Andrea; Sala, Andrea

2008-04-01

To evaluate postoperative outcome of emergency surgery for acute severe mitral regurgitation (ASMR) from a multicentre experience. In six centres, 279 patients (mean age 62+/-14 years, 62% female) undergoing emergency surgery for ASMR from December 1986 to March 2007 were analysed and followed up. Aetiology included acute myocardial infarction (AMI) in 126 patients (group 1, 45%), degenerative mitral valve disease in 74 (group 2, 26%), and acute endocarditis (AE) in 79 (group 3, 28%). Preoperatively, all patients were in haemodynamic instability, with 185 patients in cardiogenic shock (66%), 184 (66%) intubated, and 61 (22%) on IABP, respectively. Valve repair was performed in 76 (27%), whereas 203 (73%) underwent valve replacement. Median follow-up (98% complete) was 70.8 months (inter-quartile range 59.8-86.66 months). Overall 30-day mortality was 22.5% (63/279). Early death was significantly lower in group 2 (p<0.001 and p=0.005 vs group 1 and 3, respectively) whereas no difference was detected between group 1 and 3. At logistic regression analysis AMI, AE, shock, left ventricular dysfunction, and coronary artery disease were predictors of early death. Overall 15-year survival was 67+/-10%. Survival was lower in group 1 (39+/-11%) than in group 2 (75+/-9%) and group 3 (77+/-10%). Cox regression found AMI, and associated coronary artery disease to be predictors of late death. Overall 15-year actuarial and actual freedom from cardiac-related events were 44+/-9% and 28+/-10%, respectively, with the worst outcome in the presence of AE. Associated coronary artery disease, AE, AMI, preoperative atrial fibrillation, and chronic renal failure were independent predictors of cardiac-related events. Emergency surgery for ASMR remains a surgical challenge for high incidence of early and late cardiac-related events, particularly in patients with associated coronary artery disease and acute endocarditis. Apparently, type of mitral valve surgical approaches (repair or replacement) did not provide any influence on postoperative outcome.

A 6-month randomized controlled trial to test the efficacy of a lifestyle intervention for weight gain management in schizophrenia

PubMed Central

2013-01-01

Background Patients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease, lifestyle and the use of medications, which are related to weight gain. Methods A multicentric, randomized, controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program (LWP). The program consists of a one-hour weekly session to discuss topics like dietary choices, lifestyle, physical activity and self-esteem with patients and their relatives. Patients were randomized into two groups: standard care (SC) and standard care plus intervention (LWP). Primary outcome was defined as the weight and body mass index (BMI). Results 160 patients participated in the study (81 in the intervention group and 79 in the SC group). On an intent to treat analysis, after three months the patients in the intervention group presented a decrease of 0.48 kg (CI 95% -0.65 to 1.13) while the standard care group showed an increase of 0.48 kg (CI 95% 0.13 to 0.83; p=0.055). At six-month follow-up, there was a significant weight decrease of −1.15 kg, (CI 95% -2.11 to 0.19) in the intervention group compared to a weight increase in the standard care group (+0.5 kg, CI 95% -0.42–1.42, p=0.017). Conclusion In conclusion, this was a multicentric randomized clinical trial with a lifestyle intervention for individuals with schizophrenia, where the intervention group maintained weight and presented a tendency to decrease weight after 6 months. It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight. Clinicaltrials.gov identifier NCT01368406 PMID:23418863

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

PubMed

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

2016-10-01

Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO 2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

ParallABEL: an R library for generalized parallelization of genome-wide association studies.

PubMed

Sangket, Unitsa; Mahasirimongkol, Surakameth; Chantratita, Wasun; Tandayya, Pichaya; Aulchenko, Yurii S

2010-04-29

Genome-Wide Association (GWA) analysis is a powerful method for identifying loci associated with complex traits and drug response. Parts of GWA analyses, especially those involving thousands of individuals and consuming hours to months, will benefit from parallel computation. It is arduous acquiring the necessary programming skills to correctly partition and distribute data, control and monitor tasks on clustered computers, and merge output files. Most components of GWA analysis can be divided into four groups based on the types of input data and statistical outputs. The first group contains statistics computed for a particular Single Nucleotide Polymorphism (SNP), or trait, such as SNP characterization statistics or association test statistics. The input data of this group includes the SNPs/traits. The second group concerns statistics characterizing an individual in a study, for example, the summary statistics of genotype quality for each sample. The input data of this group includes individuals. The third group consists of pair-wise statistics derived from analyses between each pair of individuals in the study, for example genome-wide identity-by-state or genomic kinship analyses. The input data of this group includes pairs of SNPs/traits. The final group concerns pair-wise statistics derived for pairs of SNPs, such as the linkage disequilibrium characterisation. The input data of this group includes pairs of individuals. We developed the ParallABEL library, which utilizes the Rmpi library, to parallelize these four types of computations. ParallABEL library is not only aimed at GenABEL, but may also be employed to parallelize various GWA packages in R. The data set from the North American Rheumatoid Arthritis Consortium (NARAC) includes 2,062 individuals with 545,080, SNPs' genotyping, was used to measure ParallABEL performance. Almost perfect speed-up was achieved for many types of analyses. For example, the computing time for the identity-by-state matrix was linearly reduced from approximately eight hours to one hour when ParallABEL employed eight processors. Executing genome-wide association analysis using the ParallABEL library on a computer cluster is an effective way to boost performance, and simplify the parallelization of GWA studies. ParallABEL is a user-friendly parallelization of GenABEL.

Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure.

PubMed

McConnell, E E; Axten, C; Hesterberg, T W; Chevalier, J; Miiller, W C; Everitt, J; Oberdörster, G; Chase, G R; Thevenaz, P; Kotin, P

1999-09-01

Fiberglass (FG) is the largest category of man-made mineral fibers (MMVFs). Many types of FG are manufactured for specific uses building insulation, air handling, filtration, and sound absorption. In the United States, > 95% of FG produced is for building insulation. Several inhalation studies in rodents of FG building insulation have shown no indication of pulmonary fibrosis or carcinogenic activity. However, because of increasing use and potential for widespread human exposure, a chronic toxicity/carcinogenicity inhalation study of a typical building insulation FG (MMVF 10a) was conducted in hamsters, which were shown to be highly sensitive to the induction of mesotheliomas with another MMVF. A special-application FG (MMVF 33) and amosite asbestos were used for comparative purposes. Groups of 140 weanling male Syrian golden hamsters were exposed via nose-only inhalation for 6 h/day, 5 days/wk for 78 wk to either filtered air (chamber controls) or MMVF 10a, MMVF 33, or amosite asbestos at 250-300 WHO fibers/cm(3) with two additional amosite asbestos groups at 25 and 125 WHO fibers/cm(3). They were then held unexposed for 6 wk until approximately 10-20% survival. After 13, 26, 52, and 78 wk, various pulmonary parameters and lung fiber burdens were evaluated. Groups hamsters were removed from exposure at 13 and 52 wk and were held until 78 wk (recovery groups). Initial lung deposition of long fibers (>20 microm in length) after a single 6-h exposure was similar for all 3 fibers exposed to 250-300 fibers/cm(3). MMVF 10a lungs showed inflammation (which regressed in recovery hamsters) but no pulmonary or pleural fibrosis or neoplasms. MMVF 33 induced more severe inflammation and mild interstitial and pleural fibrosis by 26 wk that progressed in severity until 52 wk, after which it plateaued. While the inflammatory lesions regressed in the recovery animals, pulmonary or pleural fibrosis did not. A single multicentric mesothelioma was observed at 32 wk. No neoplasms were found in the remainder of the study. Amosite asbestos produced dose-related inflammation and pulmonary and pleural fibrosis as early as 13 wk in all 3 exposure levels. The lesions progressed during the course of the study, and at 78 wk severe pulmonary fibrosis with large areas of consolidation was observed in the highest 2 exposure groups. Progressive pleural fibrosis with mesothelial hypertrophy and hyperplasia was present in the thoracic wall and diaphragm in most animals and increased with time in the recovery hamsters. While no pulmonary neoplasms were observed in the amosite exposed hamsters, a large number of mesotheliomas were found; 25 fibers/cm(3), 3.6%; 125 fibers/cm(3), 25.9%; and 250 fibers/cm(3), 19.5%. For the 3 fiber types, the severity of the lung and pleural lesions generally paralleled the cumulative fiber burden, especially those >20 microm length, in the lung, thoracic wall, and diaphragm. They also inversely paralleled the in vitro dissolution rates; that is, the faster the dissolution, the lower were the cumulative lung burdens and the less severe the effects.

Rationale and design of the SOluble guanylate Cyclase stimulatoR in heArT failurE Studies (SOCRATES).

PubMed

Pieske, Burkert; Butler, Javed; Filippatos, Gerasimos; Lam, Carolyn; Maggioni, Aldo Pietro; Ponikowski, Piotr; Shah, Sanjiv; Solomon, Scott; Kraigher-Krainer, Elisabeth; Samano, Eliana Tibana; Scalise, Andrea Viviana; Müller, Katharina; Roessig, Lothar; Gheorghiade, Mihai

2014-09-01

The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement. The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel-group, placebo-controlled, double-blind, multicentre studies, SOCRATES-REDUCED (in patients with LVEF <45%) and SOCRATES-PRESERVED (in those with LVEF ≥ 45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once-daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES-REDUCED is change in NT-proBNP at 12 weeks. The primary endpoints in SOCRATES-PRESERVED are change in NT-proBNP and left atrial volume at 12 weeks. SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event-driven clinical outcome trials with sGC stimulators in this patient population. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

A classification prognostic score to predict OS in stage IV well-differentiated neuroendocrine tumors

PubMed Central

Pusceddu, Sara; Barretta, Francesco; Trama, Annalisa; Botta, Laura; Milione, Massimo; Buzzoni, Roberto; De Braud, Filippo; Mazzaferro, Vincenzo; Pastorino, Ugo; Seregni, Ettore; Mariani, Luigi; Gatta, Gemma; Di Bartolomeo, Maria; Femia, Daniela; Prinzi, Natalie; Coppa, Jorgelina; Panzuto, Francesco; Antonuzzo, Lorenzo; Bajetta, Emilio; Brizzi, Maria Pia; Campana, Davide; Catena, Laura; Comber, Harry; Dwane, Fiona; Fazio, Nicola; Faggiano, Antongiulio; Giuffrida, Dario; Henau, Kris; Ibrahim, Toni; Marconcini, Riccardo; Massironi, Sara; Žakelj, Maja Primic; Spada, Francesca; Tafuto, Salvatore; Van Eycken, Elizabeth; Van der Zwan, Jan Maaten; Žagar, Tina; Giacomelli, Luca; Miceli, Rosalba; Aroldi, Francesca; Bongiovanni, Alberto; Berardi, Rossana; Brighi, Nicole; Cingarlini, Sara; Cauchi, Carolina; Cavalcoli, Federica; Carnaghi, Carlo; Corti, Francesca; Duro, Marilina; Davì, Maria Vittoria; De Divitiis, Chiara; Ermacora, Paola; La Salvia, Anna; Luppi, Gabriele; Lo Russo, Giuseppe; Nichetti, Federico; Raimondi, Alessandra; Perfetti, Vittorio; Razzore, Paola; Rinzivillo, Maria; Siesling, Sabine; Torchio, Martina; Van Dijk, Boukje; Visser, Otto; Vernieri, Claudio

2018-01-01

No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three ‘field-practice’ cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses. PMID:29559553

A randomised controlled multicentre trial of women's and men's satisfaction with two models of antenatal education.

PubMed

Bergström, Malin; Kieler, Helle; Waldenström, Ulla

2011-12-01

To study women's and men's satisfaction with two models of antenatal education: natural childbirth preparation with psychoprophylaxis, and standard antenatal education including preparation for childbirth and parenthood but no psychoprophylaxis. Randomised controlled multicentre trial. 15 Antenatal clinics in Sweden between January 2006 and May 2007. 1087 Nulliparous women and 1064 of their partners. Both models had four two-hour sessions during pregnancy and one session post partum. The natural model was manual-based and focused on childbirth preparation, including psychoprophylaxis. In the standard care model, the group leader was free to choose her teaching approach, with an equal amount of time allocated to preparation for childbirth and for parenthood. Women's and men's evaluation of antenatal education at three months post partum. The proportion of women and men in each model that expressed satisfaction with the education were compared using χ(2) test. More women and men in the natural groups were satisfied with the education compared with the standard care groups: women 76% versus 68% (p = 0.03) and men 73% versus 65% (p = 0.03). The figures were similar for satisfaction with the childbirth preparation component: 78% and 62% in women (p < 0.001), and 79% and 67% in men (p < 0.001) in the natural and standard care groups, respectively. Fewer participants were satisfied with the parenthood preparation component, but the proportions were higher in the standard care groups: women 37% versus 32% (p < 0.001) and men 23% versus 20% (p < 0.001). A structured manual-based model of antenatal education which focuses on childbirth preparation with psychoprophylaxis may better meet expectant parents' expectations than standard antenatal education in Sweden. Copyright © 2010 Elsevier Ltd. All rights reserved.

Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS–NSTEMI randomized trial

PubMed Central

Layland, Jamie; Oldroyd, Keith G.; Curzen, Nick; Sood, Arvind; Balachandran, Kanarath; Das, Raj; Junejo, Shahid; Ahmed, Nadeem; Lee, Matthew M.Y.; Shaukat, Aadil; O'Donnell, Anna; Nam, Julian; Briggs, Andrew; Henderson, Robert; McConnachie, Alex; Berry, Colin; Hannah, Andrew; Stewart, Andrew; Metcalfe, Malcolm; Norrie, John; Chowdhary, Saqib; Clark, Andrew; Henderson, Robert; Balachandran, Kanarath; Berry, Colin; Baird, Gordon; O'Donnell, Anna; Sood, Arvind; Curzen, Nick; Das, Raj; Ford, Ian; Layland, Jamie; Junejo, Shahid; Oldroyd, Keith

2015-01-01

Aim We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. Methods and results We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. Conclusion In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness. PMID:25179764

Effect of family nursing therapeutic conversations on health-related quality of life, self-care and depression among outpatients with heart failure: A randomized multi-centre trial.

PubMed

Østergaard, Birte; Mahrer-Imhof, Romy; Wagner, Lis; Barington, Torben; Videbæk, Lars; Lauridsen, Jørgen

2018-03-07

To evaluate the short-term (3 months) effects of family nursing therapeutic conversations (FNTC) on health-related quality of life, self-care and depression in outpatients with Heart failure (HF). A randomised multi-centre trial was conducted in three Danish HF clinics. The control group (n = 167) received usual care, and the intervention group (n = 180) received FNTCs as supplement to usual care. Primary outcome was clinically significant changes (6 points) in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score between groups. Secondary outcomes were changes in self-care behaviour and depression scores. Data were assessed before first consultation and repeated after three months. No statistically significant difference was found in the change of KCCQ, self-care and depression scores between the groups. KCCQ scores of patients in the FNTC group changed clinically significant in seven domains, compared to one domain in the control group, with the highest improvement in self-efficacy, social limitation and symptom burden. FNTC was not superior to standard care of patients with HF regarding health-related quality of life, self-care and depression. Addressing the impact of the disease on the family, might improve self-efficacy, social limitation and symptom burden in patients with heart failure. Copyright © 2018 Elsevier B.V. All rights reserved.

EVIDENT 3 Study: A randomized, controlled clinical trial to reduce inactivity and caloric intake in sedentary and overweight or obese people using a smartphone application

PubMed Central

Recio-Rodriguez, José I.; Gómez-Marcos, Manuel A.; Agudo-Conde, Cristina; Ramirez, Ignasi; Gonzalez-Viejo, Natividad; Gomez-Arranz, Amparo; Salcedo-Aguilar, Fernando; Rodriguez-Sanchez, Emiliano; Alonso-Domínguez, Rosario; Sánchez-Aguadero, Natalia; Gonzalez-Sanchez, Jesus; Garcia-Ortiz, Luis

2018-01-01

Abstract Introduction: Mobile technology, when included within multicomponent interventions, could contribute to more effective weight loss. The objective of this project is to assess the impact of adding the use of the EVIDENT 3 application, designed to promote healthy living habits, to traditional modification strategies employed for weight loss. Other targeted behaviors (walking, caloric-intake, sitting time) and outcomes (quality of life, inflammatory markers, measurements of arterial aging) will also be evaluated. Methods: Randomized, multicentre clinical trial with 2 parallel groups. The study will be conducted in the primary care setting and will include 700 subjects 20 to 65 years, with a body mass index (27.5–40 kg/m2), who are clinically classified as sedentary. The primary outcome will be weight loss. Secondary outcomes will include change in walking (steps/d), sitting time (min/wk), caloric intake (kcal/d), quality of life, arterial aging (augmentation index), and pro-inflammatory marker levels. Outcomes will be measured at baseline, after 3 months, and after 1 year. Participants will be randomly assigned to either the intervention group (IG) or the control group (CG). Both groups will receive the traditional primary care lifestyle counseling prior to randomization. The subjects in the IG will be lent a smartphone and a smartband for a 3-month period, corresponding to the length of the intervention. The EVIDENT 3 application integrates the information collected by the smartband on physical activity and the self-reported information by participants on daily food intake. Using this information, the application generates recommendations and personalized goals for weight loss. Discussion: There is a great diversity in the applications used obtaining different results on lifestyle improvement and weight loss. The populations studied are not homogeneous and generate different results. The results of this study will help our understanding of the efficacy of new technologies, combined with traditional counseling, towards reducing obesity and enabling healthier lifestyles. Ethics and dissemination: The study was approved by the Clinical Research Ethics Committee of the Health Area of Salamanca (“CREC of Health Area of Salamanca”) on April 2016. A SPIRIT checklist is available for this protocol. The trial was registered in ClinicalTrials.gov provided by the US National Library of Medicine-number NCT03175614. PMID:29480874

Rationale of the BREAst cancer e-healTH [BREATH] multicentre randomised controlled trial: An Internet-based self-management intervention to foster adjustment after curative breast cancer by decreasing distress and increasing empowerment

PubMed Central

2012-01-01

Background After completion of curative breast cancer treatment, patients go through a transition from patient to survivor. During this re-entry phase, patients are faced with a broad range of re-entry topics, concerning physical and emotional recovery, returning to work and fear of recurrence. Standard and easy-accessible care to facilitate this transition is lacking. In order to facilitate adjustment for all breast cancer patients after primary treatment, the BREATH intervention is aimed at 1) decreasing psychological distress, and 2) increasing empowerment, defined as patients’ intra- and interpersonal strengths. Methods/design The non-guided Internet-based self-management intervention is based on cognitive behavioural therapy techniques and covers four phases of recovery after breast cancer (Looking back; Emotional processing; Strengthening; Looking ahead). Each phase of the fully automated intervention has a fixed structure that targets consecutively psychoeducation, problems in everyday life, social environment, and empowerment. Working ingredients include Information (25 scripts), Assignment (48 tasks), Assessment (10 tests) and Video (39 clips extracted from recorded interviews). A non-blinded, multicentre randomised controlled, parallel-group, superiority trial will be conducted to evaluate the effectiveness of the BREATH intervention. In six hospitals in the Netherlands, a consecutive sample of 170 will be recruited of women who completed primary curative treatment for breast cancer within 4 months. Participants will be randomly allocated to receive either usual care or usual care plus access to the online BREATH intervention (1:1). Changes in self-report questionnaires from baseline to 4 (post-intervention), 6 and 10 months will be measured. Discussion The BREATH intervention provides a psychological self-management approach to the disease management of breast cancer survivors. Innovative is the use of patients’ own strengths as an explicit intervention target, which is hypothesized to serve as a buffer to prevent psychological distress in long-term survivorship. In case of proven (cost) effectiveness, the BREATH intervention can serve as a low-cost and easy-accessible intervention to facilitate emotional, physical and social recovery of all breast cancer survivors. Trial registration This study is registered at the Netherlands Trial Register (NTR2935) PMID:22958799

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

PubMed Central

Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

2011-01-01

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

Ultrasound in polycystic ovary syndrome--the measuring of ovarian stroma and relationship with circulating androgens: results of a multicentric study.

PubMed

Fulghesu, A M; Angioni, S; Frau, E; Belosi, C; Apa, R; Mioni, R; Xamin, N; Capobianco, G P; Dessole, S; Fruzzetti, F; Lazzarini, V; Minerba, L; Melis, G B; Lanzone, A

2007-09-01

The introduction of transvaginal approach in ultrasound (US) has enabled the accurate evaluation of the structure of the ovary and stroma. Stroma represents an acknowledged US marker for polycystic ovary syndrome (PCOS). The proportion revealed between the stroma and the ovary surface in the median section (S/A ratio) had been indicated as a reliable marker for hyperandrogenism. In order to verify the feasibility of this determination in routine use and to confirm the efficacy of S/A ratio in predicting hyperandrogenism in PCOS, a multicentric study was performed in association with five Italian research groups. A total of 418 subjects of fertile age presenting oligomenorrhoea or secondary amenorrhoea, enlarged ovaries measuring >10 cm(3) and/or >12 follicles measuring 2-9 mm in diameter took part in the study. Clinical, US and hormonal evaluations were performed in the early follicular phase or on random days in amenorrhoeic subjects. US assessment included ovarian volume, follicle number, ovarian and stroma area in median section. The hormonal study included a baseline plasma determination of LH, FSH, estradiol (E(2)), androstenedione (A), testosterone (T), dehydroepiandrosteronesulphate, 17-hydroxy-progesterone, sex hormone-binding globulin and prolactin. Correlations and receiver operator curves were used in statistical analysis of data. S/A was found to be the best significant predictor of elevated A and T levels. In order to ascertain significant cut-off values in relation to A and T levels Youden indexes were calculated and indicated 0.32 as the best cut-off for the S/A ratio. This work underlines the importance of stroma measure in improving US diagnosis of PCOS and suggest that this parameter may be used in routine clinical practice. In fact, multicentre study demonstrated the easy feasibility of such procedure without need of sophisticated machines or intensive training for operators.

DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytren's contracture.

PubMed

Räisänen, Mikko P; Karjalainen, Teemu; Göransson, Harry; Reito, Aleksi; Kautiainen, Hannu; Malmivaara, Antti; Leppänen, Olli V

2018-03-28

Dupuytren's contracture (DC) is a chronic fibroproliferative disorder of the palmar fascia which leads to flexion contracture in one or more fingers. There is no definitive cure for DC, and treatment aims at relieving symptoms by releasing the contracture using percutaneous or operative techniques. We planned a prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of (1) collagenase clostridium histolyticum injection followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and (3) primary limited fasciectomy during short-term and long-term follow-up for Tubiana I-III stages DC. We will recruit participants from seven national centres in Finland. Primary outcome is the rate of success in the treatment arm at 5 years after recruitment. Success is a composite outcome comprising (1) at least 50% contracture release from the date of recruitment and (2) participants in a patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of contracture, (2) quick disabilities of the arm, a shoulder and hand outcome measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major adverse events, (6) patient's trust of the treatment, (7) global rating, (8) rate of PASS, (9) rate of minimal clinically important improvement, (10) expenses, (11) progression of disease, (12) progression-free survival, (13) favoured treatment modality, (14) patients achieving full contracture release and >50% improvement and (15) patient satisfaction with the treatment effect. Predictive factors for achieving the PASS will also be analysed. The protocol was approved by the Tampere University Hospital Institutional Review Board and Finnish Medicine Agency. The study will be performed according to the principles of good clinical practice. The results of the trial will be disseminated as published articles in peer-reviewed journals. NCT03192020; 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.

Are power calculations useful? A multicentre neuroimaging study

PubMed Central

Suckling, John; Henty, Julian; Ecker, Christine; Deoni, Sean C; Lombardo, Michael V; Baron-Cohen, Simon; Jezzard, Peter; Barnes, Anna; Chakrabarti, Bhismadev; Ooi, Cinly; Lai, Meng-Chuan; Williams, Steven C; Murphy, Declan GM; Bullmore, Edward

2014-01-01

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources. PMID:24644267

A randomized controlled trial of the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea.

PubMed

Moses, R G; Kalra, S; Brook, D; Sockler, J; Monyak, J; Visvanathan, J; Montanaro, M; Fisher, S A

2014-05-01

To evaluate the efficacy and safety of saxagliptin as add-on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea. In this 24-week, multicentre, randomized, parallel-group, double-blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m(2) and inadequate glycaemic control, received saxagliptin 5 mg or placebo once-daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight. A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between-group difference in adjusted mean change from baseline, -0.66%; 95% confidence interval (CI), -0.86 to -0.47 (7 mmol/mol, -9.4 to -5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and -0.6 kg for placebo (p = 0.0272). Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated. © 2013 John Wiley & Sons Ltd.

A randomized controlled trial into the effects of neurofeedback, methylphenidate, and physical activity on EEG power spectra in children with ADHD.

PubMed

Janssen, Tieme W P; Bink, Marleen; Geladé, Katleen; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

2016-05-01

The clinical and neurophysiological effects of neurofeedback (NF) as treatment for children with ADHD are still unclear. This randomized controlled trial (RCT) examined electroencephalogram (EEG) power spectra before and after NF compared to methylphenidate (MPH) treatment and physical activity (PA) - as semi-active control group - during resting and active (effortful) task conditions to determine whether NF can induce sustained alterations in brain function. Using a multicentre three-way parallel group RCT design, 112 children with a DSM-IV diagnosis of ADHD, aged between 7 and 13 years, were initially included. NF training consisted of 30 sessions of theta/beta training at Cz over a 10-week period. PA training was a semi-active control group, matched in frequency and duration. Methylphenidate was titrated using a double-blind placebo controlled procedure in 6 weeks, followed by a stable dose for 4 weeks. EEG power spectra measures during eyes open (EO), eyes closed (EC) and task (effortful) conditions were available for 81 children at pre- and postintervention (n = 29 NF, n = 25 MPH, n = 27 PA). Train Your Brain? Exercise and Neurofeedback Intervention for ADHD, https://clinicaltrials.gov/show/;NCT01363544, Ref. No. NCT01363544. Both NF and MPH resulted in comparable reductions in theta power from pre- to postintervention during the EO condition compared to PA (ηp (2)  = .08 and .12). For NF, greater reductions in theta were related to greater reductions in ADHD symptoms. During the task condition, only MPH showed reductions in theta and alpha power compared to PA (ηp (2)  = .10 and .12). This study provides evidence for specific neurophysiological effects after theta/beta NF and MPH treatment in children with ADHD. However, for NF these effects did not generalize to an active task condition, potentially explaining reduced behavioural effects of NF in the classroom. © 2016 Association for Child and Adolescent Mental Health.

Comparative effect of two Mediterranean diets versus a low-fat diet on glycaemic control in individuals with type 2 diabetes.

PubMed

Lasa, A; Miranda, J; Bulló, M; Casas, R; Salas-Salvadó, J; Larretxi, I; Estruch, R; Ruiz-Gutiérrez, V; Portillo, M P

2014-07-01

Although benefits have been attributed to the Mediterranean diet, its effect on glycaemic control has not been totally elucidated. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects. A multicentric parallel trial was conducted on 191 participants (77 men and 114 women) of the PREDIMED study in order to compare three dietary interventions: two Mediterranean diets supplemented with virgin olive oil (n=67; body mass index (BMI)=29.4±2.9) or mixed nuts (n=74; BMI=30.1±3.1) and a low-fat diet (n=50; BMI=29.8±2.8). There were no drop-outs. Changes in body weight and waist circumference were determined. Insulin resistance was measured by HOMA-IR index, adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up. Increased values of adiponectin/leptin ratio (P=0.043, P=0.001 and P<0.001 for low-fat, olive oil and nut diets, respectively) and adiponectin/HOMA-IR ratio (P=0.061, P=0.027 and P=0.069 for low-fat, olive oil and nut diets, respectively) and decreased values of waist circumference (P=0.003, P=0.001 and P=0.001 for low-fat, olive oil and nut diets, respectively) were observed in the three groups. In both Mediterranean diet groups, but not in the low-fat diet group, this was associated with a significant reduction in body weight (P=0.347, P=0.003 and P=0.021 for low-fat, olive oil and nut diets, respectively). Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet.

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

PubMed

Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

2009-09-19

Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. ZonMw.

Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients. Multicentre Study Group.

PubMed

Presterl, E; Graninger, W

1994-04-01

In a non-comparative multicentre trial 51 patients aged 24 days to 17 years received treatment with intravenous or oral fluconazole for suspected systemic fungal infections. Twenty-seven patients had confirmed infections, 26 being confirmed mycologically and 1 histologically. All isolates were Candida species. Of the 43 clinically assessed patients, 30 were considered cured, 7 improved and 6 experienced failure of therapy. Of 27 patients with confirmed fungal infections, 25 were assessed mycologically and all but one were considered cured. Of the six patients experiencing clinical failure, two had a confirmed infection and only one of these experienced mycological failure. This patient had a primary diagnosis of candidemia with persistence of Candida albicans and Candida parapsilosis. All 51 patients were evaluable for safety. No treatment-related adverse events required termination of treatment. Treatment-related side effects (diarrhea, vomiting, deafness) were reported by three of 51 patients, three patients had laboratory test abnormalities possibly related to fluconazole treatment, including elevation of liver enzyme levels and of the eosinophil count. Results of this study confirm the efficacy and safety of fluconazole in the treatment of pediatric patients with severe fungal infection.

24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial.

PubMed

Soininen, Hilkka; Solomon, Alina; Visser, Pieter Jelle; Hendrix, Suzanne B; Blennow, Kaj; Kivipelto, Miia; Hartmann, Tobias

2017-12-01

Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial. LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1:1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705. Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0·028 (SD 0·453) in the active group and -0·108 (0·528) in the control group; estimated mean treatment difference was 0·098 (95% CI -0·041 to 0·237; p=0·166). The decline in the control group was less than the prestudy estimate of -0·4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0·487), none of which were regarded as related to the study intervention. The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. European Commission 7th Framework Programme. Copyright © 2017 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.

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/.

Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

PubMed

Stott, David J; Gussekloo, Jacobijn; Kearney, Patricia M; Rodondi, Nicolas; Westendorp, Rudi G J; Mooijaart, Simon; Kean, Sharon; Quinn, Terence J; Sattar, Naveed; Hendry, Kirsty; Du Puy, Robert; Den Elzen, Wendy P J; Poortvliet, Rosalinde K E; Smit, Jan W A; Jukema, J Wouter; Dekkers, Olaf M; Blum, Manuel; Collet, Tinh-Hai; McCarthy, Vera; Hurley, Caroline; Byrne, Stephen; Browne, John; Watt, Torquil; Bauer, Douglas; Ford, Ian

2017-02-03

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.

Texting to Reduce Alcohol Misuse (TRAM): main findings from a randomized controlled trial of a text message intervention to reduce binge drinking among disadvantaged men.

PubMed

Crombie, Iain K; Irvine, Linda; Williams, Brian; Sniehotta, Falko F; Petrie, Dennis; Jones, Claire; Norrie, John; Evans, Josie M M; Emslie, Carol; Rice, Peter M; Slane, Peter W; Humphris, Gerry; Ricketts, Ian W; Melson, Ambrose J; Donnan, Peter T; Hapca, Simona M; McKenzie, Andrew; Achison, Marcus

2018-06-01

To test the effectiveness of a theoretically based text-message intervention to reduce binge drinking among socially disadvantaged men. A multi-centre parallel group, pragmatic, individually randomized controlled trial. Community-based study conducted in four regions of Scotland. A total of 825 men aged 25-44 years recruited from socially disadvantaged areas who had two or more episodes of binge drinking (> 8 UK units on a single occasion) in the preceding 28 days: 411 men were randomized to the intervention and 414 to the control. A series of 112 interactive text messages was delivered by mobile phone during a 12-week period. The intervention was structured around the Health Action Process Approach, a comprehensive model which allows integration of a range of evidence-based behaviour change techniques. The control group received 89 texts on general health, with no mention of alcohol or use of behaviour change techniques. The primary outcome measure was the proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) at 12 months post-intervention. The proportion of men consuming > 8 units on three or more occasions (in the previous 28 days) was 41.5% in the intervention group and 47.8% in the control group. Formal analysis showed that there was no evidence that the intervention was effective [odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.57-1.08; absolute reduction 5.7%, 95% CI = -13.3 to 1.9]. The Bayes factor for this outcome was 1.3, confirming that the results were inconclusive. The retention was high and similar in intervention (84.9%) and control (86.5%) groups. Most men in the intervention group engaged with the text messages: almost all (92%) replied to text messages and 67% replied more than 10 times. A theoretically based text-messaging intervention aimed at reducing binge drinking in disadvantaged men was not found to reduce prevalence of binge drinking at 12-month follow-up. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

A comparison between orthogonal and parallel plating methods for distal humerus fractures: a prospective randomized trial.

PubMed

Lee, Sang Ki; Kim, Kap Jung; Park, Kyung Hoon; Choy, Won Sik

2014-10-01

With the continuing improvements in implants for distal humerus fractures, it is expected that newer types of plates, which are anatomically precontoured, thinner and less irritating to soft tissue, would have comparable outcomes when used in a clinical study. The purpose of this study was to compare the clinical and radiographic outcomes in patients with distal humerus fractures who were treated with orthogonal and parallel plating methods using precontoured distal humerus plates. Sixty-seven patients with a mean age of 55.4 years (range 22-90 years) were included in this prospective study. The subjects were randomly assigned to receive 1 of 2 treatments: orthogonal or parallel plating. The following results were assessed: operating time, time to fracture union, presence of a step or gap at the articular margin, varus-valgus angulation, functional recovery, and complications. No intergroup differences were observed based on radiological and clinical results between the groups. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes, mean operation time, union time, or complication rates. There were no cases of fracture nonunion in either group; heterotrophic ossification was found 3 patients in orthogonal plating group and 2 patients in parallel plating group. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes or complication rates. However, orthogonal plating method may be preferred in cases of coronal shear fractures, where posterior to anterior fixation may provide additional stability to the intraarticular fractures. Additionally, parallel plating method may be the preferred technique used for fractures that occur at the most distal end of the humerus.

Uptake and efficacy of a systematic intensive smoking cessation intervention using motivational interviewing for smokers hospitalised for an acute coronary syndrome: a multicentre before-after study with parallel group comparisons.

PubMed

Auer, Reto; Gencer, Baris; Tango, Rodrigo; Nanchen, David; Matter, Christian M; Lüscher, Thomas Felix; Windecker, Stephan; Mach, François; Cornuz, Jacques; Humair, Jean-Paul; Rodondi, Nicolas

2016-09-20

To compare the efficacy of a proactive approach with a reactive approach to offer intensive smoking cessation intervention using motivational interviewing (MI). Before-after comparison in 2 academic hospitals with parallel comparisons in 2 control hospitals. Academic hospitals in Switzerland. Smokers hospitalised for an acute coronary syndrome (ACS). In the intervention hospitals during the intervention phase, a resident physician trained in MI systematically offered counselling to all smokers admitted for ACS, followed by 4 telephone counselling sessions over 2 months by a nurse trained in MI. In the observation phase, the in-hospital intervention was offered only to patients whose clinicians requested a smoking cessation intervention. In the control hospitals, no intensive smoking cessation intervention was offered. The primary outcome was 1 week smoking abstinence (point prevalence) at 12 months. Secondary outcomes were the number of smokers who received the in-hospital smoking cessation intervention and the duration of the intervention. In the intervention centres during the intervention phase, 87% of smokers (N=193/225) received a smoking cessation intervention compared to 22% in the observational phase (p<0.001). Median duration of counselling was 50 min. During the intervention phase, 78% received a phone follow-up for a median total duration of 42 min in 4 sessions. Prescription of nicotine replacement therapy at discharge increased from 18% to 58% in the intervention phase (risk ratio (RR): 3.3 (95% CI 2.4 to 4.3; p≤0.001). Smoking cessation at 12-month increased from 43% to 51% comparing the observation and intervention phases (RR=1.20, 95% CI 0.98 to 1.46; p=0.08; 97% with outcome assessment). In the control hospitals, the RR for quitting was 1.02 (95% CI 0.84 to 1.25; p=0.8, 92% with outcome assessment). A proactive strategy offering intensive smoking cessation intervention based on MI to all smokers hospitalised for ACS significantly increases the uptake of smoking cessation counselling and might increase smoking abstinence at 12 months. 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/

Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D™ trial.

PubMed

Groop, Per-Henrik; Cooper, Mark E; Perkovic, Vlado; Sharma, Kumar; Schernthaner, Guntram; Haneda, Masakazu; Hocher, Berthold; Gordat, Maud; Cescutti, Jessica; Woerle, Hans-Juergen; von Eynatten, Maximilian

2015-11-01

Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D™), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5 mg or placebo in addition to their stable glucose-lowering background therapy for 24 weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24 weeks with α = 0.05. MARLINA-T2D™ is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease. © The Author(s) 2015.

Diphtheria, tetanus and poliovirus antibody persistence 5 years after vaccination of pre-schoolers with two different diphtheria, tetanus and inactivated poliomyelitis vaccines (Td-IPV or DT-IPV) and immune responses to a booster dose of DTaP-IPV.

PubMed

Gajdos, Vincent; Vidor, Emmanuel; Richard, Patrick; Tran, Clément; Sadorge, Christine

2015-07-31

This follow-up study assessed the 5-year persistence of vaccine-induced antibodies (Td-IPV or DT-IPV) and the immune response to a booster dose of DTaP-IPV. This was an open-label, parallel-group (two arms), multicentre trial performed at 44 study sites in France. Children aged 11-13 years, of either sex, who received Td-IPV (Revaxis(®)) and DT-IPV (DT Polio(®)) vaccines at 6 years of age in one previous open-label trial with no further vaccination against diphtheria, tetanus, pertussis or poliomyelitis, were enrolled. All participants received a single intramuscular booster dose (0.5mL) of DTaP-IPV vaccine (Tetravac-Acellulaire(®)). Study endpoints were based on antibody persistence and post-booster immune responses. Safety was monitored throughout the study. Descriptive statistics were used for all analyses. Of the 758 children included in the previous study, 274 were included in this follow-up study; 129 had previously been vaccinated with Td-IPV, and 145 had previously received DT-IPV. At least 96.5% of participants in both groups presented an anti-diphtheria and anti-tetanus concentration ≥0.01IU/mL, and anti-poliovirus types 1-3 titres≥8 (1/dilution). Following vaccination with DTaP-IPV, anti-diphtheria and anti-tetanus antibody concentrations ≥0.1IU/mL and anti-poliovirus types 1-3 antibody titres ≥8 (1/dilution) were achieved in all participants. DTaP-IPV was well tolerated in this study. There were no serious adverse events during the study, and no participant withdrew because of adverse events. The present study confirmed the long-term immunity conferred by Td-IPV when given as a booster dose, and supports the use of Td-IPV as a second booster at 6 years of age in children previously vaccinated against diphtheria, tetanus and poliomyelitis types 1-3. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of XenX™, the latest ureteric occlusion device with guide wire utility: results from a prospective multicentric comparative study.

PubMed

Sanguedolce, Francesco; Montanari, Emanuele; Alvarez-Maestro, Mario; Macchione, Nicola; Hruby, Stephan; Papatsoris, Athanasios; Kallidonis, Panagiotis; Villa, Luca; Honeck, Patrick; Traxer, Olivier; Greco, Francesco

2016-11-01

This is a prospective multicentric comparative study evaluating the performance of XenX-a new dual-purpose device for the prevention of stone fragments migration during ureteroscopic lithotripsy (URS). Between March 2014 and January 2015, 41 patients undertaking URS + XenX were matched with 41 patients undergoing standard URS. Patients included had unilateral ureteric stone(s) of 0.5-1.5 cm in maximum size. Demographics, complication rates and surgical outcomes were recorded for comparison. A Likert-like 5-grade scoring system was used for surgeons' evaluation of XenX properties. Cost analysis was performed by comparing weighted mean costs of the relevant procedures. Patients' characteristics between the two groups were comparable. Lasering time was longer for XenX group (13.59 vs. 5.17 min; p = 0.0001) whilst use of basket and need of JJ stent insertion was more frequent in control group (19.5 vs. 97.6 %; p = 0.0001 and 22 vs. 35 %; p = 0.001, respectively). Intra-operative SFR was significantly higher for XenX group (100 vs. 85.4 %; p = 0.0001), but not at 4-week follow-up, after ancillary procedures were needed in 17.1 % of the control group. Surgeons' evaluations for XenX were suboptimal for "Ease of Basketing" (2/5) and "Advancement of double J stent" (3/5). The use of XenX increased costs of procedures, but spared the costs associated to ancillary procedures and stent removals. XenX confirmed to be a safe and effective device especially for the treatment of upper ureteric tract stones; moreover, XenX may reduce the risk for the need of auxiliary procedures and for the insertion of a JJ stent.

A parallel form of the Gudjonsson Suggestibility Scale.

PubMed

Gudjonsson, G H

1987-09-01

The purpose of this study is twofold: (1) to present a parallel form of the Gudjonsson Suggestibility Scale (GSS, Form 1); (2) to study test-retest reliabilities of interrogative suggestibility. Three groups of subjects were administered the two suggestibility scales in a counterbalanced order. Group 1 (28 normal subjects) and Group 2 (32 'forensic' patients) completed both scales within the same testing session, whereas Group 3 (30 'forensic' patients) completed the two scales between one week and eight months apart. All the correlations were highly significant, giving support for high 'temporal consistency' of interrogative suggestibility.

The prevalence and specific characteristics of hospitalised pressure ulcer patients: A multicentre cross-sectional study.

PubMed

Zhou, Qing; Yu, Ting; Liu, Yuan; Shi, Ruifen; Tian, Suping; Yang, Chaoxia; Gan, Huaxiu; Zhu, Yanying; Liang, Xia; Wang, Ling; Wu, Zhenhua; Huang, Jinping; Hu, Ailing

2018-02-01

To ascertain the pressure ulcer prevalence in secondary and tertiary general hospitals in different areas of Guangdong Province in China and explore the possible risk factors that are related to pressure ulcers. Few multicentre studies have been conducted on pressure ulcer prevalence in Chinese hospitals. A cross-sectional study design was used. Data from a total of 25,264 patients were included in the analysis at 25 hospitals in China. The investigators were divided into two groups. The investigators in group 1 examined the patients' skin. When a pressure ulcer was found, a pressure ulcer assessment form was completed. The investigators in group 2 provided guidance to the nurses, who assessed all patients and completed another questionnaire. A multivariate logistic regression analysis was used to analyse the relationship between the possible risk factors and pressure ulcer. The overall prevalence rate of pressure ulcers in the 25 hospitals ranged from 0%-3.49%, with a mean of 1.26%. The most common stage of the pressure ulcers was stage II (41.4%); most common anatomical locations were sacrum (39.5%) and the feet (16.4%). Braden score (p < .001), expected length of stay (p < .001), incontinence (p < .001), care group (p = .011), hospital location (p < .001), type of hospitals (p = .004), ages of patients (p < .001) were associations of pressure ulcers from the multivariate logistic regression analysis. The overall prevalence rate of pressure ulcers in Chinese hospitals was lower than that reported in previous investigations. Specific characteristics of pressure ulcer patients were as follows: low Braden score, longer expected length of stay, double incontinence, an ICU and a medical ward, hospital location in the Pearl River Delta, a university hospital and an older patient. The survey could make managers know their prevalence level of pressure ulcers and provide priorities for clinical nurses. © 2017 John Wiley & Sons Ltd.

Glucocorticoids predict 10-year fragility fracture risk in a population-based ambulatory cohort of men and women: Canadian Multicentre Osteoporosis Study (CaMos)

PubMed Central

Pallan, Shelley; Papaioannou, Alexandra; Mulgund, Manisha; Rios, Lorena; Ma, Jinhui; Thabane, Lehana; Davison, Kenneth S.; Josse, Robert G.; Kovacs, Christopher S.; Kreiger, Nancy; Olszynski, Wojciech P.; Prior, Jerilynn C.; Towheed, Tanveer; Adachi, Jonathan D.

2016-01-01

Summary We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. Purpose Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. Methods We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. Results In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR=1.5, 95 % confidence interval [CI]=1.1, 2.0), hip (HR=2.1, 95 % CI=1.1, 4.0), and any fracture (HR=1.4, 95 % CI=1.0, 1.8) compared with never GC treatment. Conclusions GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions. PMID:24577853

Issues in conducting cross-cultural research: implementation of an agreed international protocol [corrected] designed by the WHOQOL Group for the conduct of focus groups eliciting the quality of life of older adults.

PubMed

Hawthorne, Graeme; Davidson, Natasha; Quinn, Kathryn; McCrate, Farah; Winkler, Ines; Lucas, Ramona; Kilian, Reinhold; Molzahn, Anita

2006-09-01

Multi-centre and cross-cultural research require the use of common protocols if the results are to be either pooled or compared. All too often adherence to protocols is not discussed in reports and where it is reported poor adherence is frequently noted. This paper discusses the use of international guidelines developed by WHOQOL Field Centres to conduct and report focus groups aimed at eliciting key concepts of quality of life among older adults. This was the first step in the development of the WHOQOL-OLD instrument. Although there was overall adherence to the agreed guidelines, there were some differences in the level of reporting, even after participating Field Centres had the opportunity to explain their reports. The reasons for these discrepancies are reported. It is concluded that because of local situations, it is difficult to achieve identical implementation of multi-centre cross-cultural protocols and that the highest standards of auditing are required if findings are to be compared. Suggestions for how such protocols can be improved are given.

Magnetic Resonance Enterography to Assess Multifocal and Multicentric Bowel Endometriosis.

PubMed

Nyangoh Timoh, Krystel; Stewart, Zelda; Benjoar, Mikhael; Beldjord, Selma; Ballester, Marcos; Bazot, Marc; Thomassin-Naggara, Isabelle; Darai, Emile

To prospectively determine the accuracy of magnetic resonance enterography (MRE) compared with conventional magnetic resonance imaging (MRI) for multifocal (i.e., multiple lesions affecting the same digestive segment) and multicentric (i.e., multiple lesions affecting several digestive segments) bowel endometriosis. A prospective study (Canadian Task Force classification II-2). Tenon University Hospital, Paris, France. Patients with MRI-suspected colorectal endometriosis scheduled for colorectal resection from April 2014 to February 2016 were included. Patients underwent both 1.5-Tesla MRI and MRE as well as laparoscopically assisted and open colorectal resections. The diagnostic performance of MRI and MRE was evaluated for sensitivity, specificity, positive and negative predictive values, accuracy, and positive and negative likelihood ratios (LRs). The interobserver variability of the experienced and junior radiologists was quantified using weighted statistics. Forty-seven patients were included. Twenty-two (46.8%) patients had unifocal lesions, 14 (30%) had multifocal lesions, and 11 (23.4%) had multicentric lesions. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multifocal lesions were 0.29 (6/21), 1.00 (23/24), 15.36, and 0.71 for MRI and 0.57 (12/21), 0.89 (23/25), 4.95, and 0.58 for MRE. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multicentric lesions were 0.18 (1/11), 1.00 (1/1), 15, and 0.80 for MRI and 0.46 (5/11), 0.92 (33/36), 5.45, and 0.60 for MRE. Lower accuracies for MRI compared with MRE to diagnose multicentric (p = .01) and multifocal lesions (p = .004) were noted. The interobserver agreement for MRE was good for both multifocality (κ = 0.80) and multicentricity (κ = 0.61). MRE has better accuracy for diagnosing multifocal and multicentric bowel endometriosis than conventional MRI. Copyright © 2018. Published by Elsevier Inc.

Oxidative Stress Induced in Nurses by Exposure to Preparation and Handling of Antineoplastic Drugs in Mexican Hospitals: A Multicentric Study

PubMed Central

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; SanJuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses. PMID:24719678

Oxidative stress induced in nurses by exposure to preparation and handling of antineoplastic drugs in Mexican hospitals: a multicentric study.

PubMed

Gómez-Oliván, Leobardo Manuel; Miranda-Mendoza, Gerardo Daniel; Cabrera-Galeana, Paula Anel; Galar-Martínez, Marcela; Islas-Flores, Hariz; Sanjuan-Reyes, Nely; Neri-Cruz, Nadia; García-Medina, Sandra

2014-01-01

The impact of involuntary exposure to antineoplastic drugs (AD) was studied in a group of nurses in diverse hospitals in Mexico. The results were compared with a group of unexposed nurses. Anthropometric characteristics and the biochemical analysis were analyzed in both groups. Also, lipid peroxidation level (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were evaluated in blood of study participants as oxidative stress (OS) biomarkers. The group of occupationally exposed (OE) nurses consisted of 30 individuals ranging in age from 25 to 35 years. The control group included 30 nurses who were not occupationally exposed to the preparation and handling of AD and whose anthropometric and biochemical characteristics were similar to those of the OE group. All biomarkers evaluated were significantly increased (P < 0.5) in OE nurses compared to the control group. Results show that the assessment of OS biomarkers is advisable in order to evaluate exposure to AD in nurses.

The benefits and tolerance of exercise in myasthenia gravis (MGEX): study protocol for a randomised controlled trial.

PubMed

Birnbaum, Simone; Hogrel, Jean-Yves; Porcher, Raphael; Portero, Pierre; Clair, Bernard; Eymard, Bruno; Demeret, Sophie; Bassez, Guillaume; Gargiulo, Marcela; Louët, Estelle; Berrih-Aknin, Sonia; Jobic, Asmaa; Aegerter, Philippe; Thoumie, Philippe; Sharshar, Tarek

2018-01-18

Research exploring the effects of physical exercise in auto-immune myasthenia gravis (MG) is scarce. The few existing studies present methodological shortcomings limiting the conclusions and generalisability of results. It is hypothesised that exercise could have positive physical, psychological as well as immunomodulatory effects and may be a beneficial addition to current pharmacological management of this chronic disease. The aim of this study is to evaluate the benefits on perceived quality of life (QOL) and physical fitness of a home-based physical exercise program compared to usual care, for patients with stabilised, generalised auto-immune MG. MGEX is a multi-centre, interventional, randomised, single-blind, two-arm parallel group, controlled trial. Forty-two patients will be recruited, aged 18-70 years. Following a three-month observation period, patients will be randomised into a control or experimental group. The experimental group will undertake a 40-min home-based physical exercise program using a rowing machine, three times a week for three months, as an add-on to usual care. The control group will receive usual care with no additional treatment. All patients will be followed up for a further three months. The primary outcome is the mean change in MGQOL-15-F score between three and six months (i.e. pre-intervention and immediately post-intervention periods). The MGQOL-15-F is an MG-specific patient-reported QOL questionnaire. Secondary outcomes include the evaluation of deficits and functional limitations via MG-specific clinical scores (Myasthenia Muscle Score and MG-Activities of Daily Living scale), muscle force and fatigue, respiratory function, free-living physical activity as well as evaluations of anxiety, depression, self-esteem and overall QOL with the WHO-QOL BREF questionnaire. Exercise workload will be assessed as well as multiple safety measures (ECG, biological markers, medication type and dosage and any disease exacerbation or crisis). This is the largest randomised controlled trial to date evaluating the benefits and tolerance of physical exercise in this patient population. The comprehensive evaluations using standardised outcome measures should provide much awaited information for both patients and the scientific community. This study is ongoing. ClinicalTrials.gov, NCT02066519 . Registered on 13 January 2014.

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study

PubMed Central

Koek, Mayke BG; Buskens, Erik; Steegmans, Paul HA; van Weelden, Huib; Bruijnzeel-Koomen, Carla AFM; Sigurdsson, Vigfús

2006-01-01

Background Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). Methods We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. Discussion In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. Trial registration Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930 PMID:16882343

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study.

PubMed

Koek, Mayke B G; Buskens, Erik; Steegmans, Paul H A; van Weelden, Huib; Bruijnzeel-Koomen, Carla A F M; Sigurdsson, Vigfús

2006-08-01

Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT00150930.

Why did an effective Dutch complex psycho-social intervention for people with dementia not work in the German healthcare context? Lessons learnt from a process evaluation alongside a multicentre RCT.

PubMed

Voigt-Radloff, Sebastian; Graff, Maud; Leonhart, Rainer; Hüll, Michael; Rikkert, Marcel Olde; Vernooij-Dassen, Myrra

2011-08-09

Background The positive effects of the Dutch Community Occupational Therapy in Dementia programme on patients' daily functioning were not found in a multicentre randomised controlled trial (RCT) in Germany. Objectives To evaluate possible effect modification on the primary outcome within the German RCT with regard to (1) participant characteristics, (2) treatment performance and (3) healthcare service utilisation; and (4) to compare the design and primary outcome between the German and the original Dutch study. Methods (1) The impact of participant baseline data on the primary outcome was analysed in exploratory ANCOVA and regression analyses. (2) Therapists completed questionnaires on context and performance problems. The main problems were identified by a qualitative content analysis and focus-group discussion. Associations of the primary outcome with scores of participant adherence and treatment performance were evaluated by regression analysis. (3) Utilisation rates of healthcare services were controlled for significant group differences. (4) Differences in the Dutch and German study design were identified, and the primary outcome was contrasted at the item level. Results (1) Participant characteristics could not explain more than 5% of outcome variance. (2) The treatment performance of some active intervention components was poor but not significantly associated with the primary outcome. (3) There were no significant group differences in the utilisation of healthcare resources. (4) In contrast to the Dutch waiting-control group, the active intervention in the German control group may have reduced group differences in the current RCT. The German patients demonstrated a higher independence at baseline and less improvement in instrumental activities of daily living. Conclusion The differences in outcome may be explained by a more active control treatment, partially poor experimental treatment and less room for improvement in the German sample. Future cross-national transfers should be prepared by pilot studies assessing the applicability of the intervention and patient needs specific to the target country. Trial registration International Clinical Trials Registry Platform, DRKS00000053.

Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial.

PubMed

Griffin, Damian; Parsons, Nick; Shaw, Ewart; Kulikov, Yuri; Hutchinson, Charles; Thorogood, Margaret; Lamb, Sarah E

2014-07-24

To investigate whether surgery by open reduction and internal fixation provides benefit compared with non-operative treatment for displaced, intra-articular calcaneal fractures. Pragmatic, multicentre, two arm, parallel group, assessor blinded randomised controlled trial (UK Heel Fracture Trial). 22 tertiary referral hospitals, United Kingdom. 151 patients with acute displaced intra-articular calcaneal fractures randomly allocated to operative (n=73) or non-operative (n=78) treatment. The primary outcome measure was patient reported Kerr-Atkins score for pain and function (scale 0-100, 100 being the best possible score) at two years after injury. Secondary outcomes were complications; hindfoot pain and function (American Orthopaedic Foot and Ankle Society score); general health (SF-36); quality of life (EQ-5D); clinical examination; walking speed; and gait symmetry. Analysis was by intention to treat. 95% follow-up was achieved for the primary outcome (69 in operative group and 74 in non-operative group), and a complete set of secondary outcomes were available for 75% of participants. There was no significant difference in the primary outcome (mean Kerr-Atkins score 69.8 in operative group v 65.7 in non-operative group; adjusted 95% confidence interval of difference -7.1 to 7.0) or in any of the secondary outcomes between treatment groups. Complications and reoperations were more common in those who received operative care (estimated odds ratio 7.5, 95% confidence interval 2.0 to 41.8). Operative treatment compared with non-operative care showed no symptomatic or functional advantage after two years in patients with typical displaced intra-articular fractures of the calcaneus, and the risk of complications was higher after surgery. Based on these findings, operative treatment by open reduction and internal fixation is not recommended for these fractures.Trial registration Current Controlled Trials ISRCTN37188541. © Griffin et al 2014.

Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy.

PubMed

Chronowski, G M; Ha, C S; Wilder, R B; Cabanillas, F; Manning, J; Cox, J D

2001-08-01

Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Copyright 2001 American Cancer Society.

Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial

PubMed Central

Lundell, L; Attwood, S; Ell, C; Fiocca, R; Galmiche, J-P; Hatlebakk, J; Lind, T; Junghard, O

2008-01-01

Background: With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported. Methods: LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan–Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol. Results: 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS. Conclusions: Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD. PMID:18469091

IntAct: Intraoperative Fluorescence Angiography (IFA) to Prevent Anastomotic Leak in Rectal Cancer Surgery: A Randomised Controlled Trial.

PubMed

Armstrong, G; Croft, J; Corrigan, N; Brown, J M; Goh, V; Quirke, P; Hulme, C; Tolan, D; Kirby, A; Cahill, R; O'Connell, R; Miskovic, D; Coleman, M; Jayne, D G

2018-05-11

Anastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, rates of AL have remained static at around 10-15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (Indocyanine Green) and near-infrared laparoscopy can minimise the rate of anastomotic leak as compared to conventional white light laparoscopy. Two mechanistic sub-studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies. IntAct is a prospective, unblinded, parallel group, multicentre, European, randomised controlled trial comparing surgery with intraoperative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end-point is rate of clinical anastomotic leak at 90-days following surgery. Secondary endpoints include all AL (clinical and radiological), change in planned anastomosis, complications and re-interventions, use of stoma, cost effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over three years, 880 patients from 25 European centres will be recruited and followed up for 90 days. IntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Randomised sham-controlled double-blind multicentre clinical trial to ascertain the effect of percutaneous radiofrequency treatment for lumbar facet joint pain.

PubMed

van Tilburg, C W J; Stronks, D L; Groeneweg, J G; Huygen, F J P M

2016-11-01

The aim of this study was to compare the effect of a percutaneous radiofrequency heat lesion at the medial branch of the primary dorsal ramus with a sham procedure, for the treatment of lumbar facet joint pain. A randomised sham-controlled double blind multicentre trial was carried out at the multidisciplinary pain centres of two hospitals. A total of 60 patients aged > 18 years with a history and physical examination suggestive of facet joint pain and a decrease of ≥ 2 on a numerical rating scale (NRS 0 to 10) after a diagnostic facet joint test block were included. In the treatment group, a percutaneous radiofrequency heat lesion (80 o C during 60 seconds per level) was applied to the medial branch of the primary dorsal ramus. In the sham group, the same procedure was undertaken without for the radiofrequency lesion. Both groups also received a graded activity physiotherapy programme. The primary outcome measure was decrease in pain. A secondary outcome measure was the Global Perceived Effect scale (GPE). There was a statistically significant effect on the level of pain in the factor Period (T0-T1). However, there was no statistically significant difference with the passage of time between the groups (Group × Period) or in the factor Group. In the crossover group, 11 of 19 patients had a decrease in NRS of ≥ 2 at one month crossover (p = 0.65). There was no statistically significant difference in satisfaction with the passage of time between the groups (Group × Period). The independent factors Group and Period also showed no statistically significant difference. There was no statistically significant Group × Period effect for recovery, neither an effect of Group or of Period. The null hypothesis of no difference in the decrease in pain and in GPE between the treatment and sham groups cannot be rejected. Post hoc analysis revealed that the age of the patients and the severity of the initial pain significantly predicted a positive outcome. Cite this article: Bone Joint J 2016;98-B:1526-33. ©2016 The British Editorial Society of Bone & Joint Surgery.

Design and rationale of the MR-INFORM study: stress perfusion cardiovascular magnetic resonance imaging to guide the management of patients with stable coronary artery disease.

PubMed

Hussain, Shazia T; Paul, Matthias; Plein, Sven; McCann, Gerry P; Shah, Ajay M; Marber, Michael S; Chiribiri, Amedeo; Morton, Geraint; Redwood, Simon; MacCarthy, Philip; Schuster, Andreas; Ishida, Masaki; Westwood, Mark A; Perera, Divaka; Nagel, Eike

2012-09-19

In patients with stable coronary artery disease (CAD), decisions regarding revascularisation are primarily driven by the severity and extent of coronary luminal stenoses as determined by invasive coronary angiography. More recently, revascularisation decisions based on invasive fractional flow reserve (FFR) have shown improved event free survival. Cardiovascular magnetic resonance (CMR) perfusion imaging has been shown to be non-inferior to nuclear perfusion imaging in a multi-centre setting and superior in a single centre trial. In addition, it is similar to invasively determined FFR and therefore has the potential to become the non-invasive test of choice to determine need for revascularisation. The MR-INFORM study is a prospective, multi-centre, randomised controlled non-inferiority, outcome trial. The objective is to compare the efficacy of two investigative strategies for the management of patients with suspected CAD. Patients presenting with stable angina are randomised into two groups: 1) The FFR-INFORMED group has subsequent management decisions guided by coronary angiography and fractional flow reserve measurements. 2) The MR-INFORMED group has decisions guided by stress perfusion CMR. The primary end-point will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at one year. Clinical trials.gov identifier NCT01236807. MR INFORM will assess whether an initial strategy of CMR perfusion is non-inferior to invasive angiography supplemented by FFR measurements to guide the management of patients with stable coronary artery disease. Non-inferiority of CMR perfusion imaging to the current invasive reference standard (FFR) would establish CMR perfusion imaging as an attractive non-invasive alternative to current diagnostic pathways.

Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol

PubMed Central

García‐Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin‐Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García‐Gutiérrez, Susana

2017-01-01

Abstract Aims Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. Methods We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. Conclusions The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. PMID:29154427

A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

PubMed Central

Uhl, W; Buchler, M; Malfertheiner, P; Beger, H; Adler, G; Gaus, W; the, G

1999-01-01

BACKGROUND—The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis.
AIM—To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial.
METHODS—302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 µg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis.
RESULTS—The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences.
CONCLUSIONS—This trial shows no benefit of octreotide in the treatment of acute pancreatitis.


Keywords: acute pancreatitis; somatostatin; octreotide; randomised controlled multicentre trial PMID:10369711

Penicillin sensitivity of gonococci isolated in Australia, 1981-6. Australian Gonococcal Surveillance Programme.

PubMed

1988-06-01

The sensitivity to penicillin of about 25,000 gonococcal isolates tested in Australia during the five years to 30 June 1986 was assessed in a collaborative multicentric study. Increasing resistance to the penicillin group of antibiotics was observed during the course of this study and was manifested both as increased levels of chromosomally mediated intrinsic resistance and by an increasing incidence of penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Pronounced regional differences in the levels of intrinsic resistance, the incidence of infections with PPNG, and the endemic spread of PPNG strains were observed.

Multicentric myelolipoma in a dog.

PubMed

Kamiie, Junichi; Fueki, Keisuke; Amagai, Harumi; Ichikawa, Youichiro; Shirota, Kinji

2009-03-01

We report herein a case of multicentric myelolipoma in an 11-year-old beagle dog that presented with vomiting. Laparotomy demonstrated the presence of a large mass adherent to the greater omentum and multiple small white maculae in the spleen. Cytological and histological examinations revealed that the mass and maculae comprised mature adipocytes and hematopoietic elements including granulocytic, erythrocytic and megakaryocytic series in several phases of maturation and macrophages containing hemosiderin deposits, resembling bone marrow. Multicentric myelolipoma was diagnosed. This is first report of multicentric myelolipoma in a dog.

Long‐term safety and efficacy of tofogliflozin as add‐on to insulin in patients with type 2 diabetes: Results from a 52‐week, multicentre, randomized, double‐blind, open‐label extension, Phase 4 study in Japan (J‐STEP/INS)

PubMed Central

Tamura, Masahiro; Senda, Masayuki; Gunji, Ryoji; Kaku, Kohei

2018-01-01

Aims To evaluate the long‐term safety and efficacy of tofogliflozin as an add‐on treatment to insulin over 52 weeks. Materials and methods This 52‐week, multicentre, Phase 4 study consisted of a 16‐week, randomized, double‐blind, placebo‐controlled phase and a 36‐week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%‐10.5%) receiving insulin monotherapy (basal‐bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase‐4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the ‘tofo‐tofo group’ and patients who received placebo and tofogliflozin (36 weeks) were referred to as the ‘pla‐tofo group’. Results A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment‐emergent adverse event (AE) (42.9% in the tofo‐tofo group and 29.4% in the pla‐tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo‐tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla‐tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes ± standard error from baseline to Week 52) in the tofo‐tofo and pla‐tofo groups were 8.53% (−0.76% ± 0.077) and 8.40% (−0.73% ± 0.102); 68.84 kg (−1.52 kg ± 0.207) and 72.24 kg (−2.13 kg ± 0.313), respectively. Conclusions This study demonstrates the safety and efficacy of tofogliflozin as add‐on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management. PMID:29316236

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

PubMed

Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

2015-06-27

The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Meta analysis of parallel versus perpendicular double plating for distal humerus fracture of type C in adults].

PubMed

Li, B B; Lin, F; Cai, L H; Chen, Y; Lin, Z J

2017-08-01

Objective: To evaluate the effects of parallel versus perpendicular double plating for distal humerus fracture of type C. Methods: A standardized comprehensive literature search was performed by PubMed, Embase, Cochrane library, CMB, CNKI and Medline datebase.Randomized controlled studies on comparison between parallel versus perpendicular double plating for distal humerus fracture of type C before December 2015 were enrolled in the study.All date were analyzed by the RevMan 5.2 software. Results: Six studies, including 284 patients, met the inclusion criteria.There were 155 patients in perpendicular double plating group, 129 patients in parallel double plating group.The results of Meta-analysis indicated that there were statistically significant difference between the two groups in complications ( OR =2.59, 95% CI : 1.03 to 6.53, P =0.04). There was no significant difference between the two groups in surgical duration ( MD =-1.84, 95% CI : -9.06 to 5.39, P =0.62), bone union time ( MD =0.09, 95% CI : -0.06 to 0.24, P =0.22), Mayo Elbow Performance Score ( MD =0.09, 95% CI : -0.06 to 0.24, P =0.22), Range of Motions ( MD =-0.92, 95% CI : -4.65 to 2.81, P =0.63) and the rate of excellent and good results ( OR =0.64, 95% CI : 0.27 to 1.52, P =0.31). Conclusion: Both perpendicular and parallel double plating are effective in distal humerus fracture of type C, parallel double plating has less complications.

Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycaemic control comparable to rosiglitazone/metformin tablet.

PubMed

Raskin, P; Lewin, A; Reinhardt, R; Lyness, W

2009-09-01

To assess the use of a new repaglinide/metformin fixed-dose combination (FDC) tablet for the treatment of type 2 diabetes. In this 26-week, multicentre, open-label, parallel-group trial, subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to receive a repaglinide/metformin FDC tablet either two times daily (BID) or three times daily (TID) or a rosiglitazone/metformin FDC tablet BID. The primary objective comprised two hypotheses tested in a hierarchical order: (i) that treatment with the repaglinide/metformin FDC BID is non-inferior to that of a rosiglitazone/metformin FDC tablet BID as measured by changes in haemoglobin A1c (HbA1c) (results presented here) and (ii) if true, that treatment with the repaglinide/metformin FDC BID was non-inferior to that of the repaglinide/metformin FDC TID as measured by changes in HbA1c (results presented in a companion paper). Additional efficacy and safety end-points were also assessed. Of the 561 subjects randomized, 383 completed the study. Reductions in HbA1c values became apparent at earlier times for repaglinide/metformin FDC BID treatment than rosiglitazone/metformin FDC BID, and final changes in HbA1c were not significantly different between treatment arms (p = 0.8186); thus, the predefined statistical criterion for non-inferiority was met. Overall adverse event profiles were comparable between treatment groups, and no major hypoglycaemic episodes were reported during the study. The repaglinide/metformin FDC BID regimen showed efficacy that was non-inferior to that of the rosiglitazone/metformin FDC BID regimen currently in clinical use and a more rapid reduction of HbA1c values. Thus, repaglinide/metformin FDC BID is a clinically feasible alternative to rosiglitazone/metformin FDC BID.

A multicentre randomised, 1-year comparative effectiveness, parallel-group trial protocol of a physical therapy approach compared to corticosteroid injections

PubMed Central

Deyle, Gail D; Gill, Norman W; Rhon, Daniel I; Allen, Chris S; Allison, Stephen C; Hando, Ben R; Petersen, Evan J; Dusenberry, Douglas I; Bellamy, Nicholas

2016-01-01

Introduction Corticosteroid injections (CSIs) are commonly used as an initial or a primary intervention for knee osteoarthritis (OA). Consistent evidence indicates CSIs offer symptom relief with conflicting reports regarding long-term efficacy. Physical therapy (PT) offers a non-invasive alternative. There is moderate evidence suggesting short-term and long-term symptom relief and functional improvement with PT interventions. Patients with knee OA are more commonly prescribed CSI than PT prior to total joint replacement. UnitedHealthcare and Military Health System data show substantially more total knee replacement patients receive preoperative CSI than PT. There are no studies comparing CSI to a PT approach in individuals with knee OA. The primary objective of this study is to compare the effectiveness of CSI to PT in individuals with knee OA at 1, 2 and 12 months. Methods and analysis We plan to recruit 156 participants meeting established knee OA criteria. Following informed consent, participants will be randomised to receive either CSI or PT. All participants will receive instruction on recommended exercise and weight control strategies plus usual medical care. The CSI intervention consisting of 3 injections and the PT intervention consisting of 8–12 sessions will be spaced over 12 months. Measures of the dependent variables (DVs) will occur at baseline, 4 weeks, 8 weeks, 6 months and 12 months post enrolment. This pragmatic, randomised clinical trial will be a mixed-model 2×5 factorial design. The independent variables are treatment (CSI and PT) and time with five levels from baseline to 1 year. The primary DV is the Western Ontario & McMaster Universities Arthritis Index (WOMAC). We will also compare healthcare utilisation between the 2 groups. Ethics and Dissemination The protocol was approved by the Madigan Army Medical Center Institutional Review Board. The authors intend to publish the results in a peer-reviewed source. Trial Registration Number NCT01427153. PMID:27033961

MRI of the wrist in juvenile idiopathic arthritis: proposal of a paediatric synovitis score by a consensus of an international working group. Results of a multicentre reliability study.

PubMed

Damasio, Maria Beatrice; Malattia, Clara; Tanturri de Horatio, Laura; Mattiuz, Chiara; Pistorio, Angela; Bracaglia, Claudia; Barbuti, Domenico; Boavida, Peter; Juhan, Karen Lambot; Ording, Lil Sophie Mueller; Rosendahl, Karen; Martini, Alberto; Magnano, GianMichele; Tomà, Paolo

2012-09-01

MRI is a sensitive tool for the evaluation of synovitis in juvenile idiopathic arthritis (JIA). The purpose of this study was to introduce a novel MRI-based score for synovitis in children and to examine its inter- and intraobserver variability in a multi-centre study. Wrist MRI was performed in 76 children with JIA. On postcontrast 3-D spoiled gradient-echo and fat-suppressed T2-weighted spin-echo images, joint recesses were scored for the degree of synovial enhancement, effusion and overall inflammation independently by two paediatric radiologists. Total-enhancement and inflammation-synovitis scores were calculated. Interobserver agreement was poor to moderate for enhancement and inflammation in all recesses, except in the radioulnar and radiocarpal joints. Intraobserver agreement was good to excellent. For enhancement and inflammation scores, mean differences (95 % CI) between observers were -1.18 (-4.79 to 2.42) and -2.11 (-6.06 to 1.83). Intraobserver variability (reader 1) was 0 (-1.65 to 1.65) and 0.02 (-1.39 to 1.44). Intraobserver agreement was good. Except for the radioulnar and radiocarpal joints, interobserver agreement was not acceptable. Therefore, the proposed scoring system requires further refinement.

Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes.

PubMed

Ritzel, R; Roussel, R; Bolli, G B; Vinet, L; Brulle-Wohlhueter, C; Glezer, S; Yki-Järvinen, H

2015-09-01

To conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. The EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). No significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference -0.28 kg (95% CI -0.55 to -0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events. Gla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

A multicentre cohort study assessing day of week effect and outcome from emergency appendicectomy.

PubMed

Ferguson, Henry J M; Hall, Nigel J; Bhangu, Aneel

2014-09-01

There is evidence to suggest that patients undergoing treatment at weekends may be subject to different care processes and outcomes compared with weekdays. This study aimed to determine whether clinical outcomes from weekend appendicectomy are different from those performed on weekdays. Multicentre cohort study during May-June 2012 from 95 centres (89 within the UK). The primary outcome was the 30-day adverse event rate. Multilevel modelling was used to account for clustering within hospitals while adjusting for case mix to produce adjusted ORs and 95% CIs. When compared with Monday, there were no significant differences for other days of the week considering 30-day adverse events in adjusted models. On Sunday, rates of simple appendicitis were highest, and rates of normal (OR 0.62, 95% CI 0.42 to 0.90) and complex appendicitis (OR 0.65, 95% CI 0.46 to 0.93) lowest. This was accompanied by a 43% lower likelihood in use of laparoscopy on Sunday (OR 0.47, 95% CI 0.32 to 0.69), accompanied by the lowest level of consultant presence for the week. When pooling weekends and weekdays, laparoscopy use remained less likely at the weekend (OR 0.68, 95% CI 0.55 to 0.83), with no significant difference for 30-day adverse event rate (OR 1.01, 95% CI 0.80 to 1.29). This study found that weekend appendicectomy was not associated with increased 30-day adverse events. It cannot rule out smaller increases that may be shown by larger studies. It further illustrated that patients operated on at weekends were subject to different care processes, which may expose them to risk. 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 sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

Role of Obesity Variables in Detecting Hypertension in an Iranian Population.

PubMed

Khashayar, Patricia; Aghaei Meybodi, Hamidreza; Rezaei Hemami, Mohsen; Larijani, Bagher

2017-09-01

As the high incidence of hypertension has been in conjunction with dramatic increase in the prevalence of obesity, many studies have suggested obesity as its underlying cause in diverse race and ethnic groups. The present study was designed to quantify the relationship between obesity variables and hypertension in Iranian population. A ROC curve analysis was also used to determine an optimal BMI cutoff for obesity with the aim of representing elevated incidence of hypertension in this population. The study population comprised of apparently healthy men and women who participated in the Iranian Multi-centric Osteoporosis Studies (IMOS), a multi-centric cross-sectional study carried out in urban areas of five great cities (Tehran, Tabriz, Mashhad, Shiraz and Bushehr). The anthropometric (weight, height, waist and hip circumferences) and blood pressure measures were reported in some 5724 subjects. The influence of these factors on systolic and diastolic blood pressure was assessed based on a list-wise method. There was a significant difference in the studied subjects anthropometric (weight classes (BMI), WC and HC, and WHR) and blood pressure variables; age, gender and weight, however, were the only factors significantly influencing SBP and DBP. Furthermore, BMI showed a significant impact on the overall risk of developing hypertension. General obesity rather than abdominal obesity is directly linked with higher blood pressure levels in Iranian population.

Introducing a simplified approach to insulin therapy in type 2 diabetes: a comparison of two single-dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs.

PubMed

Lankisch, M R; Ferlinz, K C; Leahy, J L; Scherbaum, W A

2008-12-01

To investigate whether the addition of a single bolus of insulin glulisine (glulisine), administered at either breakfast or main mealtime, in combination with basal insulin glargine (glargine) and oral antidiabetic drugs (OADs), provides equivalent glycaemic control in patients with type 2 diabetes, irrespective of the time of glulisine injection. A national, multicentre, randomized, open-label, parallel-group study of 393 patients with type 2 diabetes who were suboptimally controlled [haemoglobin A(1c) (HbA(1c)) > 6.5-9.0% and fasting blood glucose (BG) 7.0% at baseline and who reached HbA(1c)

NEURAPRO-E study protocol: a multicentre randomized controlled trial of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders.

PubMed

Markulev, Connie; McGorry, Patrick D; Nelson, Barnaby; Yuen, Hok Pan; Schaefer, Miriam; Yung, Alison R; Thompson, Andrew; Berger, Gregor; Mossaheb, Nilufar; Schlögelhofer, Monika; Smesny, Stefan; de Haan, Lieuwe; Riecher-Rössler, Anita; Nordentoft, Merete; Chen, Eric Yu Hai; Verma, Swapna; Hickie, Ian; Amminger, G Paul

2017-10-01

Recent research has indicated that preventative intervention is likely to benefit patients 'at-risk' for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs), coupled with the falling transition rate in ultra high-risk (UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group. This trial is a 6-month, double-blind, randomized placebo-controlled trial of 1.4 g day -1 omega-3 PUFAs in UHR patients aged between 13 and 40 years. The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive-behavioural case management (CBCM) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM. Secondary outcomes will examine symptomatic and functional changes, as well as examine if candidate risk factors predict response to omega-3 PUFA treatment in the UHR group. This is the protocol of the NeuraproE study. Utilizing a large sample, results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders, which may be the strongest avenue for reducing the burden, stigmatization, disability and economic consequences of these disorders. © 2015 Wiley Publishing Asia Pty Ltd.

A youth-led social marketing intervention to encourage healthy lifestyles, the EYTO (European Youth Tackling Obesity) project: a cluster randomised controlled0 trial in Catalonia, Spain.

PubMed

Llauradó, Elisabet; Aceves-Martins, Magaly; Tarro, Lucia; Papell-Garcia, Ignasi; Puiggròs, Francesc; Arola, Lluís; Prades-Tena, Jordi; Montagut, Marta; Moragas-Fernández, Carlota M; Solà, Rosa; Giralt, Montse

2015-07-03

The encouragement of healthy lifestyles for obesity prevention in young people is a public health priority. The European Youth Tackling Obesity (EYTO) project is a multicentric intervention project with participation from the United Kingdom, Portugal, the Czech Republic and Spain. The general aim of the EYTO project is to improve lifestyles, including nutritional habits and physical activity practice, and to prevent obesity in socioeconomically disadvantaged and vulnerable adolescents. The EYTO project works through a peer-led social marketing intervention that is designed and implemented by the adolescents of each participating country. Each country involved in the project acts independently. This paper describes the "Som la Pera" intervention Spanish study that is part of the EYTO project. In Spain, the research team performed a cluster randomised controlled intervention over 2 academic years (2013-2015) in which 2 high-schools were designated as the control group and 2 high-schools were designated as the intervention group, with a minimum of 121 schoolchildren per group. From the intervention group, 5 adolescents with leadership characteristics, called "Adolescent Challenge Creators" (ACCs), were recruited. These 5 ACCs received an initial 4 h training session about social marketing principles and healthy lifestyle theory, followed by 24 sessions (1.30 h/session) divided in two academic years to design and implement activities presented as challenges to encourage healthy lifestyles among their peers, the approximately 180-200 high-school students in the intervention group. During the design of the intervention, it was essential that the ACCs used the 8 social marketing criteria (customer orientation, behaviour, theory, insight, exchange, competition, segmentation and methods mix). The expected primary outcomes from the Spanish intervention will be as follows: increases in the consumption of fruits and vegetables and physical activity practice along with reductions in TV/computer/game console use. The secondary outcomes will be as follows: increased breakfast consumption, engagement with local recreation and reduced obesity prevalence. The outcomes will be measured by the Health Behaviour in School-aged Children Study (HBSC) survey at baseline and at the end of the intervention. In the control group, no intervention was implemented, but the outcome measurements were collected in parallel with the intervention group. This study described a new methodology to improve lifestyles and to address adolescent obesity. ClinicalTrials.gov: NCT02157402. Registered 03 June 2014.

The micronutrient intake profile of a multicentre cohort of Australian LAGB patients.

PubMed

McGrice, Melanie A; Porter, Judi A

2014-03-01

Patients who have undergone bariatric surgery have increased risks of developing micronutrient deficiencies. Translational research investigating the actual micronutrient intake of bariatric patients is limited. We examined the micronutrient intake of a multicentre cohort of laparoscopic adjustable gastric banding patients 1 year post-surgery. These data were compared to micronutrient recommendations for the general population. Consecutive patients from three bariatric surgery facilities in Melbourne, Australia, were invited to participate 12 months post-operatively. A validated food frequency questionnaire was posted to 215 prospective participants. Of the 52 participants, micronutrient intakes from food and fluids alone were below population recommendations for calcium, folate, magnesium, potassium, retinol equivalents, thiamin and vitamin E. Males did not meet the recommended intakes for zinc, and iron intakes in pre-menopausal women were insufficient. Intakes lower than recommended levels for these micronutrients suggest inadequate intake of foods from vegetable, dairy, lean meat (or alternatives) and wholegrains. Micronutrient intakes below recommended levels in this patient group can be further explained by their macronutrient intakes that suggested diets of poor nutrient density. Recommendations for supplementation in this group have wide variations, usually having been developed through the presence of clinical and biochemical deficiencies. Nutritional supplementation should be more extensive in scope and dosage than is currently recommended by some professional guidelines. Further long-term studies are needed to explore both macro- and micronutrient intakes on the morbidity and mortality of this patient population.

Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.

PubMed

Theron, Grant; Zijenah, Lynn; Chanda, Duncan; Clowes, Petra; Rachow, Andrea; Lesosky, Maia; Bara, Wilbert; Mungofa, Stanley; Pai, Madhukar; Hoelscher, Michael; Dowdy, David; Pym, Alex; Mwaba, Peter; Mason, Peter; Peter, Jonny; Dheda, Keertan

2014-02-01

The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384. Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specificity (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408). Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients. European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Employing Nested OpenMP for the Parallelization of Multi-Zone Computational Fluid Dynamics Applications

NASA Technical Reports Server (NTRS)

Ayguade, Eduard; Gonzalez, Marc; Martorell, Xavier; Jost, Gabriele

2004-01-01

In this paper we describe the parallelization of the multi-zone code versions of the NAS Parallel Benchmarks employing multi-level OpenMP parallelism. For our study we use the NanosCompiler, which supports nesting of OpenMP directives and provides clauses to control the grouping of threads, load balancing, and synchronization. We report the benchmark results, compare the timings with those of different hybrid parallelization paradigms and discuss OpenMP implementation issues which effect the performance of multi-level parallel applications.

Effectiveness of a Hospital-Based Work Support Intervention for Female Cancer Patients – A Multi-Centre Randomised Controlled Trial

PubMed Central

Tamminga, Sietske J.; Verbeek, Jos H. A. M.; Bos, Monique M. E. M.; Fons, Guus; Kitzen, Jos J. E. M.; Plaisier, Peter W.; Frings-Dresen, Monique H. W.; de Boer, Angela G. E. M.

2013-01-01

Objective One key aspect of cancer survivorship is return-to-work. Unfortunately, many cancer survivors face problems upon their return-to-work. For that reason, we developed a hospital-based work support intervention aimed at enhancing return-to-work. We studied effectiveness of the intervention compared to usual care for female cancer patients in a multi-centre randomised controlled trial. Methods Breast and gynaecological cancer patients who were treated with curative intent and had paid work were randomised to the intervention group (n = 65) or control group (n = 68). The intervention involved patient education and support at the hospital and improvement of communication between treating and occupational physicians. In addition, we asked patient's occupational physician to organise a meeting with the patient and the supervisor to make a concrete gradual return-to-work plan. Outcomes at 12 months of follow-up included rate and time until return-to-work (full or partial), quality of life, work ability, work functioning, and lost productivity costs. Time until return-to-work was analyzed with Kaplan-Meier survival analysis. Results Return-to-work rates were 86% and 83% (p = 0.6) for the intervention group and control group when excluding 8 patients who died or with a life expectancy of months at follow-up. Median time from initial sick leave to partial return-to-work was 194 days (range 14–435) versus 192 days (range 82–465) (p = 0.90) with a hazard ratio of 1.03 (95% CI 0.64–1.6). Quality of life and work ability improved statistically over time but did not differ statistically between groups. Work functioning and costs did not differ statistically between groups. Conclusion The intervention was easily implemented into usual psycho-oncological care and showed high return-to-work rates. We failed to show any differences between groups on return-to-work outcomes and quality of life scores. Further research is needed to study which aspects of the intervention are useful and which elements need improvement. Trial Registration Nederlands Trial Register (NTR) 1658 PMID:23717406

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

PubMed

Luger, T; Van Leent, E J; Graeber, M; Hedgecock, S; Thurston, M; Kandra, A; Berth-Jones, J; Bjerke, J; Christophers, E; Knop, J; Knulst, A C; Morren, M; Morris, A; Reitamo, S; Roed-Petersen, J; Schoepf, E; Thestrup-Pedersen, K; Van Der Valk, P G; Bos, J D

2001-04-01

SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

A community-based physical activity intervention to prevent mobility-related disability for retired older people (REtirement in ACTion (REACT)): study protocol for a randomised controlled trial.

PubMed

Stathi, Afroditi; Withall, Janet; Greaves, Colin J; Thompson, Janice L; Taylor, Gordon; Medina-Lara, Antonieta; Green, Colin; Bilzon, James; Gray, Selena; Johansen-Berg, Heidi; Sexton, Claire E; Western, Max J; de Koning, Jolanthe L; Bollen, Jessica C; Moorlock, Sarah J; Demnitz, Naiara; Seager, Poppy; Guralnik, Jack M; Jack Rejeski, W; Fox, Ken R

2018-04-17

The REtirement in ACTion (REACT) study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial (RCT) with an internal pilot phase. It aims to test the effectiveness and cost-effectiveness of a community, group-based physical activity intervention for reducing, or reversing, the progression of functional limitations in older people who are at high risk of mobility-related disability. A sample of 768 sedentary, community-dwelling, older people aged 65 years and over with functional limitations, but who are still ambulatory (scores between 4 and 9 out of 12 in the Short Physical Performance Battery test (SPPB)) will be randomised to receive either the REACT intervention, delivered over a period of 12 months by trained facilitators, or a minimal control intervention. The REACT study incorporates comprehensive process and economic evaluation and a nested sub-study which will test the hypothesis that the REACT intervention will slow the rate of brain atrophy and of decline in cognitive function assessed using magnetic resonance imaging (MRI). Outcome data will be collected at baseline, 6, 12 and 24 months for the main study, with MRI sub-study data collected at baseline, 6 and 12 months. The primary outcome analysis (SPPB score at 24 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. REACT represents the first large-scale, pragmatic, community-based trial in the UK to target the non-disabled but high-risk segment of the older population with an intervention to reduce mobility-related disability. A programme that can successfully engage this population in sufficient activity to improve strength, aerobic capacity, coordination and balance would have a major impact on sustaining health and independence. REACT is also the first study of its kind to conduct a full economic and comprehensive process evaluation alongside the RCT. If effective and cost-effective, the REACT intervention has strong potential to be implemented widely in the UK and elsewhere. ISRCTN, ID: ISRCTN45627165 . Retrospectively registered on 13 June 2016. Trial sponsor: University of Bath. Protocol Version 1.5.

Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

PubMed

Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina

2018-03-01

Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants. Copyright © 2018.

Evaluation of postoperative recovery in day surgery patients using a mobile phone application: a multicentre randomized trial.

PubMed

Jaensson, M; Dahlberg, K; Eriksson, M; Nilsson, U

2017-11-01

Many patients undergoing anaesthesia and surgery experience postoperative complications. Our aim was to investigate whether a systematic follow-up smartphone-based assessment, using recovery assessment by phone points (RAPP) compared with standard care, had a positive effect on day surgery patients' postoperative recovery. We also investigated whether there were differences in women and men's recovery and recovery scores. The study was a single-blind, multicentre randomized controlled trial. A total of 997 patients were randomly allocated to either RAPP or standard care. The Swedish web version of a quality of recovery (SwQoR) questionnaire was used to evaluate the patients' postoperative recovery, either on paper or using an application (RAPP) on postoperative days seven and 14. On postoperative day seven the RAPP group reported significantly better values in seven out of 24 items of the SwQoR: sleeping difficulties; not having a general feeling of wellbeing; having difficulty feeling relaxed/comfortable; and dizziness; headache; pain in the surgical wound; and a swollen surgical wound compared with the control group, implying a good postoperative recovery. Both men and women in the RAPP group reported significantly better values (and, hence good postoperative recovery) compared with the control group in the items sleeping difficulties; not having a general feeling of wellbeing and pain in the surgical wound. Measurement of patient-reported outcomes using a smartphone-based application was associated with decreased discomfort from several postoperative symptoms. Systematic e-assessment can thereby increase patients' quality of recovery and identify key areas for improvement in perioperative care. NCT02492191. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

A randomized multicentre trial to compare revascularization with optimal medical therapy for the treatment of chronic total coronary occlusions.

PubMed

Werner, Gerald S; Martin-Yuste, Victoria; Hildick-Smith, David; Boudou, Nicolas; Sianos, Georgios; Gelev, Valery; Rumoroso, Jose Ramon; Erglis, Andrejs; Christiansen, Evald Høj; Escaned, Javier; di Mario, Carlo; Hovasse, Thomas; Teruel, Luis; Bufe, Alexander; Lauer, Bernward; Bogaerts, Kris; Goicolea, Javier; Spratt, James C; Gershlick, Anthony H; Galassi, Alfredo R; Louvard, Yves

2018-05-02

The clinical value of percutaneous coronary intervention (PCI) for chronic coronary total occlusions (CTOs) is not established by randomized trials. This study should compare the benefit of PCI vs. optimal medical therapy (OMT) on the health status in patients with at least one CTO. Three hundred and ninety-six patients were enrolled in a prospective randomized, multicentre, open-label, and controlled clinical trial to compare the treatment by PCI with OMT with a 2:1 randomization ratio. The primary endpoint was the change in health status assessed by the Seattle angina questionnaire (SAQ) between baseline and 12 months follow-up. Fifty-two percent of patients have multi-vessel disease in whom all significant non-occlusive lesions were treated before randomization. An intention-to-treat analysis was performed including 13.4% failed procedures in the PCI group and 7.3% cross-overs in the OMT group. At 12 months, a greater improvement of SAQ subscales was observed with PCI as compared with OMT for angina frequency [5.23, 95% confidence interval (CI) 1.75; 8.71; P = 0.003], and quality of life (6.62, 95% CI 1.78-11.46; P = 0.007), reaching the prespecified significance level of 0.01 for the primary endpoint. Physical limitation (P = 0.02) was also improved in the PCI group. Complete freedom from angina was more frequent with PCI 71.6% than OMT 57.8% (P = 0.008). There was no periprocedural death or myocardial infarction. At 12 months, major adverse cardiac events were comparable between the two groups. Percutaneous coronary intervention leads to a significant improvement of the health status in patients with stable angina and a CTO as compared with OMT alone. NCT01760083.

ParallABEL: an R library for generalized parallelization of genome-wide association studies

PubMed Central

2010-01-01

Background Genome-Wide Association (GWA) analysis is a powerful method for identifying loci associated with complex traits and drug response. Parts of GWA analyses, especially those involving thousands of individuals and consuming hours to months, will benefit from parallel computation. It is arduous acquiring the necessary programming skills to correctly partition and distribute data, control and monitor tasks on clustered computers, and merge output files. Results Most components of GWA analysis can be divided into four groups based on the types of input data and statistical outputs. The first group contains statistics computed for a particular Single Nucleotide Polymorphism (SNP), or trait, such as SNP characterization statistics or association test statistics. The input data of this group includes the SNPs/traits. The second group concerns statistics characterizing an individual in a study, for example, the summary statistics of genotype quality for each sample. The input data of this group includes individuals. The third group consists of pair-wise statistics derived from analyses between each pair of individuals in the study, for example genome-wide identity-by-state or genomic kinship analyses. The input data of this group includes pairs of SNPs/traits. The final group concerns pair-wise statistics derived for pairs of SNPs, such as the linkage disequilibrium characterisation. The input data of this group includes pairs of individuals. We developed the ParallABEL library, which utilizes the Rmpi library, to parallelize these four types of computations. ParallABEL library is not only aimed at GenABEL, but may also be employed to parallelize various GWA packages in R. The data set from the North American Rheumatoid Arthritis Consortium (NARAC) includes 2,062 individuals with 545,080, SNPs' genotyping, was used to measure ParallABEL performance. Almost perfect speed-up was achieved for many types of analyses. For example, the computing time for the identity-by-state matrix was linearly reduced from approximately eight hours to one hour when ParallABEL employed eight processors. Conclusions Executing genome-wide association analysis using the ParallABEL library on a computer cluster is an effective way to boost performance, and simplify the parallelization of GWA studies. ParallABEL is a user-friendly parallelization of GenABEL. PMID:20429914

A randomised trial of high and low pressure level settings on an adjustable ventriculoperitoneal shunt valve for idiopathic normal pressure hydrocephalus: results of the Dutch evaluation programme Strata shunt (DEPSS) trial.

PubMed

Delwel, Ernst J; de Jong, Dirk A; Dammers, Ruben; Kurt, Erkan; van den Brink, Wimar; Dirven, Clemens M F

2013-07-01

In treating idiopathic normal pressure hydrocephalus (INPH) with a shunt there is always a risk of underdrainage or overdrainage. The hypothesis is tested whether patients treated using an adjustable valve preset at the highest opening pressure leads to comparable good clinical results with less subdural effusions than in a control group with an opening pressure preset at a low pressure level. A multicentre prospective randomised trial was performed on a total of 58 patients suspected of INPH. Thirty patients were assigned to (control) group 1 and received a Strata shunt (Medtronic, Goleta, USA) with the valve preset at a performance level (PL) of 1.0, while 28 patients were assigned to group 2 and received a Strata shunt with the valve preset at PL 2.5. In this group the PL was allowed to be lowered until improvement or radiological signs of overdrainage were met. Significantly more subdural effusions were observed in the improved patients of group 1. There was no statistically significant difference in improvement between both groups overall. On the basis of this multicentre prospective randomised trial it is to be recommended to treat patients with INPH with a shunt with an adjustable valve, preset at the highest opening pressure and lowered until clinical improvement or radiological signs of overdrainage occur although slower improvement and more shunt adjustments might be the consequence.

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Multicentre randomised controlled trial examining the cost-effectiveness of contrast-enhanced high field magnetic resonance imaging in women with primary breast cancer scheduled for wide local excision (COMICE).

PubMed

Turnbull, L W; Brown, S R; Olivier, C; Harvey, I; Brown, J; Drew, P; Hanby, A; Manca, A; Napp, V; Sculpher, M; Walker, L G; Walker, S

2010-01-01

To determine whether the addition of magnetic resonance imaging (MRI) to current patient evaluation by triple assessment would aid tumour localisation within the breast and thus reduce the reoperation rate in women with primary breast tumours who are scheduled for wide local excision (WLE), and to assess whether the addition of MRI would be cost-effective for the UK NHS. A multicentre, randomised controlled, open, parallel group trial with equal randomisation. The main design was supplemented with a qualitative study to assess patients' experiences of the treatment process and care pathway, and involved the development of a non-scheduled standardised interview (NSSI). The study took place at 45 hospitals throughout the UK. Women aged 18 years or over with biopsy-proven primary breast cancer who had undergone triple assessment, were scheduled for WLE, and were capable of providing written informed consent. Patients were randomised to receive MRI or no MR1. Randomisation was performed using minimisation, incorporating a random element. All MRI was performed at 1.5 T or 1.0 T with a dedicated bilateral breast coil. The primary end point of the trial was the reoperation rate. Secondary outcome measures included discrepancies between imaging and histopathology, and the effectiveness of using both procedures; change in clinical management after using MRI; the clinical significance of MRI-only-detected lesions; the rate of interventions; the ipsilateral tumour recurrence rate; patient quality of life (QoL); and cost-effectiveness. From a total of 1623 patients, 816 were randomised to MRI and 807 to no MRI. No differences in reoperation rates were found between the two groups of patients [MRI patients 18.75%, no MRI 19.33%, difference 0.58%, 95% confidence interval (CI) -3.24 to 4.40]. Therefore, the addition of MRI to conventional triple assessment was not found to be statistically significantly associated with a reduced reoperation rate (odds ratio = 0.96, 95% CI 0.75-1.24, p = 0.7691). The best agreement between all imaging modalities and histopathology with regard to tumour size and extent of disease was found in patients over 50 years old with ductal tumours NST and who were node negative. In the imaging arm, mastectomy was found to be pathologically avoidable for 16 (27.6%) out of 58 patients who underwent the procedure. There were no significant differences between the groups regarding the proportion of patients receiving chemotherapy, radiotherapy or additional adjuvant therapies, as well as for local recurrence-free interval rates and QoL. An acceptable NSSI was developed for use in this population of patients. Economic analysis found no difference in outcomes between the two trial arms. The addition of MRI to triple assessment did not result in a reduction in operation rates, and the use of MRI would thus consume extra resource with few or no benefits in terms of cost-effectiveness or HRQoL. However, MRI showed potential to improve tumour localisation, and preoperative biopsy of MRI-only-detected lesions is likely to minimise the incidence of inappropriate mastectomy. Current Controlled Trials ISRCTN57474502.

Multicentre experience with the BridgePoint devices to facilitate recanalisation of chronic total coronary occlusions through controlled subintimal re-entry.

PubMed

Werner, Gerald S; Schofer, Joachim; Sievert, Horst; Kugler, Chad; Reifart, Nicolaus J

2011-06-01

The major challenge for the interventional treatment of chronic total coronary occlusion (CTO) is a low primary success rate. A common problem is the passage of the recanalisation wire into a subintimal position. New devices, which were evaluated in the first multicentre study in CTOs resistant to a conventional wire approach, may help to facilitate a controlled re-entry into the true lumen. The aim of this study was to assess the safety and efficacy of this approach, with successful true lumen distal wire passage as the primary endpoint. Forty-two patients were enrolled in four centres with high expertise in PCI for CTOs. All CTOs were of at least three months duration, and were initially attempted with dedicated recanalisation wires. After failure to pass or creation of a subintimal dissection, the BridgePoint devices were applied, consisting of a ball-tipped catheter (CrossBoss) to pass the proximal occlusion cap, and a flat-shaped balloon catheter (Stingray catheter) to be inflated within the subintimal space to guide the re-entry into the true vessel lumen with a special wire (Stingray guidewire). The primary endpoint was met in 67% of all patients. A higher success rate seemed to be possible when all devices were used in sequenced beginning with the CrossBoss, and in the case of a subintimal passage, followed by the Stingray. True lumen re-entry failed because of the loss of distally contrast filling and thus loss of a target for re-entry, and by a failure to advance the Stingray balloon far enough distal and parallel to the distal lumen. There were no severe device related complications. In patients with complex CTOs referred to dedicated centres with high experience in CTOs, these results demonstrate the potential of a guided re-entry from a subintimal wire position by use of the BridgePoint devices.

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale, Multicentre Study

PubMed Central

Zheng, Lei; Yin, Yuepeng; Zou, Zhenzhen; Zhou, Feiguo; Zhou, Weiping; Shen, Feng; Gao, Chunfang

2016-01-01

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population. PMID:27070780

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Efficacy and safety of acarbose chewable tablet in patients with type 2 diabetes: a multicentre, randomized, double-blinded, double-dummy positive controlled trial.

PubMed

Wu, Qian Lin; Liu, Yu Ping; Lu, Ju Ming; Wang, Chang Jiang; Yang, Tao; Dong, Ji Xiang; Li, Cheng Jiang; Ma, Jian Hua; Xue, Yao Ming; Sun, Rui Hua; Wei, Dong; Tian, Hao Ming

2012-08-01

To evaluate the effect and safety of HbA1c and glycemic control of acarbose chewable tablets in patients with type 2 diabetic. A multicentre, randomized, double-blinded, double-dummy, positive controlled clinical trial was conducted. Two hundred thirty-four Chinese patients with type 2 diabetic were enrolled in eight clinical centres, who were divided randomly into the acarbose chewable tablet group (experimental group, n = 116) and the acarbose treatment group (control group, n = 118). Two hundred seven patients (88.5%) took part in the 12-week trial. At the beginning and end of the clinical trial, HbA1c and blood glucose as well as safety indexes were measured. After the treatment, the level of finger two-hour postprandial blood glucose (PPBG) was decreased 4.15 mmol/L (26.82%) and 3.54 mmol/L (22.77%), respectively, in the experiment group and the control group. The levels of venous two-hour PPBG in the experiment group and the control group were decreased 4.04 mmol/L (25.38%) and 2.75 mmol/L (17.26%), respectively, with the means of HbA1c lowering 11.67% and 12.44%, respectively. Fasting blood glucose (FBG) also was reduced significantly in both groups. Patients in both groups showed obvious weight reduction (P < 0.0001). There were no significant differences in the incidence of adverse events between the two groups. In summary, acarbose chewable tablets have a definite curative effect in treating type 2 diabetic patients as HbA1c and blood glucose levels decreased significantly after the 12-week treatment. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

The importance of dietary change for men diagnosed with and at risk of prostate cancer: a multi-centre interview study with men, their partners and health professionals.

PubMed

Avery, Kerry N L; Donovan, Jenny L; Horwood, Jeremy; Neal, David E; Hamdy, Freddie C; Parker, Chris; Wade, Julia; Lane, Athene

2014-05-03

The diagnosis of prostate cancer (PC) can provide a trigger for dietary change, and there is evidence that healthier diets may improve quality of life and clinical outcomes. However, men's views about dietary change in PC survivorship are largely unknown. This multi-centre qualitative interview study explored men's views about dietary change in PC survivorship, to better understand motivations for, and barriers to, achieving desired changes. The role of radical and active surveillance treatments on dietary change and the influence of men's partners were examined. Focus groups also evaluated stakeholder opinion, including healthcare professionals, about the provision of dietary advice to PC patients. A multi-centre interview study explored views about diet and motivations for, and barriers to, dietary change in men at elevated risk or diagnosed with PC following prostate specific antigen (PSA) testing. 58 men and 11 partners were interviewed. Interviews and focus groups were undertaken with 11 healthcare professionals, 5 patients and 4 partners to evaluate stakeholders' opinions about the feasibility and acceptability of providing dietary advice to PC patients. Data were analysed using methods of constant comparison and thematic analysis. Over half of diagnosed men reported making dietary changes, primarily to promote general or prostate health or facilitate coping, despite their uncertainty about diet-PC links. Interest in dietary advice was high. Information needs varied depending on treatment received, with men on active surveillance more frequently modifying their diet and regarding this as an adjunct therapy. Men considered their partners integral to implementing changes. Provision of dietary advice to men diagnosed with PC was considered by healthcare professionals and men to be feasible and appropriate in the context of a holistic 'care package'. Many men make positive dietary changes after PC diagnosis, which are perceived by men and their partners to bring psychological and general health benefits and could help future dietary intervention trials. Men and their partners desire more and better dietary information that may support PC survivorship, particularly among those embarking on active surveillance/monitoring programmes. There are opportunities for healthcare professionals to support PC patients both clinically and psychologically by the routine integration of healthy eating advice into survivorship care plans.

"Unplugged": A New European School Programme against Substance Abuse

ERIC Educational Resources Information Center

Kreeft, Peer Van Der; Wiborg, Gudrun; Galanti, Maria Rosaria; Siliquini, Roberta; Bohrn, Karl; Scatigna, Maria; Lindahl, Ann-Marie; Melero, Juan Carlos; Vassara, Maro; Faggiano, Fabrizio

2009-01-01

This paper presents the rationale, development and application of "Unplugged', a new school programme for the prevention of substance abuse, which is based on the comprehensive social influence approach (CSI). The programme was developed, implemented and evaluated by a cross-disciplinary group of experts in the frame of a multi-centre study…

Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.

PubMed

Scholz, Karl Heinrich; Maier, Sebastian K G; Maier, Lars S; Lengenfelder, Björn; Jacobshagen, Claudius; Jung, Jens; Fleischmann, Claus; Werner, Gerald S; Olbrich, Hans G; Ott, Rainer; Mudra, Harald; Seidl, Karlheinz; Schulze, P Christian; Weiss, Christian; Haimerl, Josef; Friede, Tim; Meyer, Thomas

2018-04-01

The aim of this study was to investigate the effect of contact-to-balloon time on mortality in ST-segment elevation myocardial infarction (STEMI) patients with and without haemodynamic instability. Using data from the prospective, multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial, we assessed the prognostic relevance of first medical contact-to-balloon time in n = 12 675 STEMI patients who used emergency medical service transportation and were treated with primary percutaneous coronary intervention (PCI). Patients were stratified by cardiogenic shock (CS) and out-of-hospital cardiac arrest (OHCA). For patients treated within 60 to 180 min from the first medical contact, we found a nearly linear relationship between contact-to-balloon times and mortality in all four STEMI groups. In CS patients with no OHCA, every 10-min treatment delay resulted in 3.31 additional deaths in 100 PCI-treated patients. This treatment delay-related increase in mortality was significantly higher as compared to the two groups of OHCA patients with shock (2.09) and without shock (1.34), as well as to haemodynamically stable patients (0.34, P < 0.0001). In patients with CS, the time elapsing from the first medical contact to primary PCI is a strong predictor of an adverse outcome. This patient group benefitted most from immediate PCI treatment, hence special efforts to shorten contact-to-balloon time should be applied in particular to these high-risk STEMI patients. NCT00794001.

Protocol of a mixed method, randomized controlled study to assess the efficacy of a psychosocial intervention to reduce fatigue in patients with End-Stage Renal Disease (ESRD).

PubMed

van der Borg, Wieke E; Schipper, Karen; Abma, Tineke A

2016-07-08

Patients with end-stage renal disease (ESRD) commonly suffer from severe fatigue, which strongly impacts their quality of life (QoL). Although fatigue is often attributed to disease- and treatment characteristics, research also shows that behavioural, psychological and social factors affect perceived fatigue in dialysis patients. Whereas studies on fatigue in other chronic patient groups suggest that psychological or psychosocial interventions are effective in reducing fatigue, such interventions are not yet available for ESRD patients on dialysis treatment. The objective of this study is to examine the efficacy of a psychosocial intervention for dialysis patients aimed at reducing fatigue (primary outcome) and improving QoL (secondary outcome). The intervention consists of counselling sessions led by a social worker. The implementation process and patients' and social workers' expectations and experiences with the intervention will also be evaluated. This study follows a mixed-methods design in which both quantitative and qualitative data will be collected. A multi-centre, randomised controlled trial (RCT) with repeated measures will be conducted to quantitatively assess the efficacy of the psychosocial intervention in reducing fatigue and improving QoL in ESRD patients. Additional secondary outcomes and medical parameters will be assessed. Outcomes will be compared to patients receiving usual care. A sample of 74 severely fatigued dialysis patients will be recruited from 10 dialysis centres. Patients will be randomly assigned to the intervention or control group. Outcomes will be assessed at baseline, post intervention/16 weeks, and at three and six-month follow-ups. A qualitative process evaluation will be conducted parallel to/following the effectiveness RCT. Interviews and focus groups will be conducted to gain insight into patients' and social workers' perspectives on outcomes and implementation procedures. Implementation fidelity will be assessed by audio-taped and written registrations. Participatory methods ensure the continuous input of experiential knowledge, improving the quality of study procedures and the applicability of outcomes. This is the first mixed method study (including an RCT and qualitative process evaluation) to examine the effect and implementation process of a psychosocial intervention on reducing fatigue and improving QoL in ESRD patients on dialysis treatment. NTR5366 , The Netherlands National Trial Register (NTR), registered August 26, 2015.

The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study.

PubMed

Katsurada, Naoko; Suzuki, Motoi; Aoshima, Masahiro; Yaegashi, Makito; Ishifuji, Tomoko; Asoh, Norichika; Hamashige, Naohisa; Abe, Masahiko; Ariyoshi, Koya; Morimoto, Konosuke

2017-12-06

Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities. This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status. A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53-1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54-7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01-0.70) but not with chronic respiratory disease. These effects were not affected by age group. The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults.

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

Neubert, Antje; Baarslag, Manuel Alberto; Dijk, Monique van; Rosmalen, Joost van; 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

2017-06-21

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. 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. 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. EudraCT: 2014-003582-24; Clinicaltrials.gov: NCT02509273; 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.

Prehospital endotracheal intubation and chest tubing does not prolong the overall resuscitation time of severely injured patients: a retrospective, multicentre study of the Trauma Registry of the German Society of Trauma Surgery.

PubMed

Kulla, Martin; Helm, Matthias; Lefering, Rolf; Walcher, Felix

2012-06-01

The aim of this study was to determine whether prehospital endotracheal intubation (ETI) and chest tube placement is unnecessarily time consuming in severely injured patients. A retrospective, multicentre study including all adult patients (ISS ≥9; 2002-7) of the Trauma Registry of the German Society of Trauma Surgery who were not secondarily transferred to a trauma centre and received a definitive airway and a chest tube. Creating four groups: AA (n=963) receiving ETI and chest tube on scene, AB (n=1547) ETI performed in the prehospital setting but chest tubing later in the emergency department (ED) and BB (n=640) receiving both procedures in the ED. The BA collective (ETI performed in the ED, but chest tubing on scene) was excluded from the study because of the small sample size (n=41). The trauma resuscitation time (TRT), demographic data, injuries, treatment and outcome of the remaining three collectives were compared. The prehospital TRT of the AA collective was longer than the AB and BB subgroups (80±37 min vs 77±44 min 65±46 min; p<0.01). Although the AA and AB subgroups were more severely injured (ISS 35±15 vs 38±15 vs 31±12; p<0.01) and showed poorer vital parameters on scene, the overall TRT (accident until end of ED treatment) were equal for all three groups (152±59 min vs 151±62 min vs 148±68 min; p=0.07). The TRISS adjusted mortality was also equal in all three groups. In a physician-based emergency medical service, prehospital ETI and chest tube placement do not prolong the total TRT of severely injured patients.

Evaluation of the McGrath MAC and Macintosh laryngoscope for tracheal intubation in 2000 patients undergoing general anaesthesia: the randomised multicentre EMMA trial study protocol

PubMed Central

Kriege, Marc; Alflen, Christian; Tzanova, Irene; Schmidtmann, Irene; Piepho, Tim; Noppens, Ruediger R

2017-01-01

Introduction The direct laryngoscopy technique using a Macintosh blade is the first choice globally for most anaesthetists. In case of an unanticipated difficult airway, the complication rate increases with the number of intubation attempts. Recently, McGrath MAC (McGrath) video laryngoscopy has become a widely accepted method for securing an airway by tracheal intubation because it allows the visualisation of the glottis without a direct line of sight. Several studies and case reports have highlighted the benefit of the video laryngoscope in the visualisation of the glottis and found it to be superior in difficult intubation situations. The aim of this study was to compare the first-pass intubation success rate using the (McGrath) video laryngoscope compared with conventional direct laryngoscopy in surgical patients. Methods and analysis The EMMA trial is a multicentre, open-label, patient-blinded, randomised controlled trial. Consecutive patients requiring tracheal intubation are randomly allocated to either the McGrath video laryngoscope or direct laryngoscopy using the Macintosh laryngoscope. The expected rate of successful first-pass intubation is 95% in the McGrath group and 90% in the Macintosh group. Each group must include a total of 1000 patients to achieve 96% power for detecting a difference at the 5% significance level. Successful intubation with the first attempt is the primary endpoint. The secondary endpoints are the time to intubation, attempts for successful intubation, the necessity of alternatives, visualisation of the glottis using the Cormack & Lehane score and percentage of glottic opening score and definite complications. Ethics and dissemination The project was approved by the local ethics committee of the Medical Association of the Rhineland Palatine state and Westphalia-Lippe. The results of this study will be made available in the form of manuscripts for publication and presentations at national and international meetings. Trial registration number ClinicalTrials.gov NCT 02611986; pre-results. PMID:28827261

External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study.

PubMed

Lamain-de Ruiter, Marije; Kwee, Anneke; Naaktgeboren, Christiana A; de Groot, Inge; Evers, Inge M; Groenendaal, Floris; Hering, Yolanda R; Huisjes, Anjoke J M; Kirpestein, Cornel; Monincx, Wilma M; Siljee, Jacqueline E; Van 't Zelfde, Annewil; van Oirschot, Charlotte M; Vankan-Buitelaar, Simone A; Vonk, Mariska A A W; Wiegers, Therese A; Zwart, Joost J; Franx, Arie; Moons, Karel G M; Koster, Maria P H

2016-08-30

 To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy.  External validation of all published prognostic models in large scale, prospective, multicentre cohort study.  31 independent midwifery practices and six hospitals in the Netherlands.  Women recruited in their first trimester (<14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded.  Discrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots.  3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated. The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit.  In this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact. 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.

Differential Item Functioning in the SF-36 Physical Functioning and Mental Health Sub-Scales: A Population-Based Investigation in the Canadian Multicentre Osteoporosis Study.

PubMed

Lix, Lisa M; Wu, Xiuyun; Hopman, Wilma; Mayo, Nancy; Sajobi, Tolulope T; Liu, Juxin; Prior, Jerilynn C; Papaioannou, Alexandra; Josse, Robert G; Towheed, Tanveer E; Davison, K Shawn; Sawatzky, Richard

2016-01-01

Self-reported health status measures, like the Short Form 36-item Health Survey (SF-36), can provide rich information about the overall health of a population and its components, such as physical, mental, and social health. However, differential item functioning (DIF), which arises when population sub-groups with the same underlying (i.e., latent) level of health have different measured item response probabilities, may compromise the comparability of these measures. The purpose of this study was to test for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scale items in a Canadian population-based sample. Study data were from the prospective Canadian Multicentre Osteoporosis Study (CaMos), which collected baseline data in 1996-1997. DIF was tested using a multiple indicators multiple causes (MIMIC) method. Confirmatory factor analysis defined the latent variable measurement model for the item responses and latent variable regression with demographic and health status covariates (i.e., sex, age group, body weight, self-perceived general health) produced estimates of the magnitude of DIF effects. The CaMos cohort consisted of 9423 respondents; 69.4% were female and 51.7% were less than 65 years. Eight of 10 items on the PF sub-scale and four of five items on the MH sub-scale exhibited DIF. Large DIF effects were observed on PF sub-scale items about vigorous and moderate activities, lifting and carrying groceries, walking one block, and bathing or dressing. On the MH sub-scale items, all DIF effects were small or moderate in size. SF-36 PF and MH sub-scale scores were not comparable across population sub-groups defined by demographic and health status variables due to the effects of DIF, although the magnitude of this bias was not large for most items. We recommend testing and adjusting for DIF to ensure comparability of the SF-36 in population-based investigations.

Cost-efficiency of specialist inpatient rehabilitation for working-aged adults with complex neurological disabilities: a multicentre cohort analysis of a national clinical data set.

PubMed

Turner-Stokes, Lynne; Williams, Heather; Bill, Alan; Bassett, Paul; Sephton, Keith

2016-02-24

To evaluate functional outcomes, care needs and cost-efficiency of specialist rehabilitation for a multicentre cohort of inpatients with complex neurological disability, comparing different diagnostic groups across 3 levels of dependency. A multicentre cohort analysis of prospectively collected clinical data from the UK Rehabilitation Outcomes Collaborative (UKROC) national clinical database, 2010-2015. All 62 specialist (levels 1 and 2) rehabilitation services in England. Working-aged adults (16-65 years) with complex neurological disability. all episodes with length of stay (LOS) 8-400 days and complete outcome measures recorded on admission and discharge. Total N=5739: acquired brain injury n=4182 (73%); spinal cord injury n=506 (9%); peripheral neurological conditions n=282 (5%); progressive conditions n=769 (13%). Specialist inpatient multidisciplinary rehabilitation. Dependency and care costs: Northwick Park Dependency Scale/Care Needs Assessment (NPDS/NPCNA). Functional independence: UK Functional Assessment Measure (UK Functional Independence Measure (FIM)+FAM). Cost-efficiency: (1) time taken to offset rehabilitation costs by savings in NPCNA-estimated costs of ongoing care, (2) FIM efficiency (FIM gain/LOS days), (3) FIM+FAM efficiency (FIM+FAM gain/LOS days). Patients were analysed in 3 groups of dependency. Mean LOS 90.1 (SD 66) days. All groups showed significant reduction in dependency between admission and discharge on all measures (paired t tests: p<0.001). Mean reduction in 'weekly care costs' was greatest in the high-dependency group at £760/week (95% CI 726 to 794)), compared with the medium-dependency (£408/week (95% CI 370 to 445)), and low-dependency (£130/week (95% CI 82 to 178)), groups. Despite longer LOS, time taken to offset the cost of rehabilitation was 14.2 (95% CI 9.9 to 18.8) months in the high-dependency group, compared with 22.3 (95% CI 16.9 to 29.2) months (medium dependency), and 27.7 (95% CI 15.9 to 39.7) months (low dependency). FIM efficiency appeared greatest in medium-dependency patients (0.54), compared with the low-dependency (0.37) and high-dependency (0.38) groups. Broadly similar patterns were seen across all 4 diagnostic groups. Specialist rehabilitation can be highly cost-efficient for all neurological conditions, producing substantial savings in ongoing care costs, especially in high-dependency patients. 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/

Induced endometrial trauma (endometrial scratch) in the mid-luteal menstrual cycle phase preceding first cycle IVF/ICSI versus usual IVF/ICSI therapy: study protocol for a randomised controlled trial.

PubMed

Pye, Clare; Chatters, Robin; Cohen, Judith; Brian, Kate; Cheong, Ying C; Laird, Susan; Mohiyiddeen, Lamiya; Skull, Jonathan; Walters, Stephen; Young, Tracey; Metwally, Mostafa

2018-05-20

Endometrial trauma commonly known as endometrial scratch (ES) has been shown to improve pregnancy rates in women with a history of repeated implantation failure undergoing in vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI). However, the procedure has not yet been fully explored in women having IVF/ICSI for the first time. This study aims to examine the effect of performing an ES in the mid-luteal phase prior to a first-time IVF/ICSI cycle on the chances of achieving a clinical pregnancy and live birth. If ES can influence this success rate, there would be a significant cost saving to the National Health Service through decreasing the number of IVF/ICSI cycles necessary to achieve a pregnancy, increase the practice of single embryo transfer and consequently have a large impact on risks and costs associated with multiple pregnancies. This 30-month, UK, multicentre, parallel group, randomised controlled trial includes a 9-month internal pilot and health economic analysis recruiting 1044 women from 16 fertility units. It will follow up participants to identify if IVF/ICSI has been successful and live birth has occurred up to 6 weeks post partum. Primary analysis will be on an intention-to-treat basis. A substudy of endometrial samples obtained during the ES will assess the role of immune factors in embryo implantation. Main trial recruitment commenced on January 2017 and is ongoing.Participants randomised to the intervention group will receive the ES procedure in the mid-luteal phase of the preceding cycle prior to first-time IVF/ICSI treatment versus usual IVF/ICSI treatment in the control group, with 1:1 randomisation. The primary outcome is live birth rate after completed 24 weeks gestation. South Central-Berkshire Research Ethics Committee approved the protocol. Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences. ISRCTN23800982; 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.

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease.

PubMed

Megna, Matteo; Patruno, Cataldo; Balato, Anna; Rongioletti, Franco; Stingeni, Luca; Balato, Nicola

2017-08-01

Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p < 0.05), itch intensity (higher in adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

PubMed

Celis-Morales, Carlos; Livingstone, Katherine M; Marsaux, Cyril F M; Forster, Hannah; O'Donovan, Clare B; Woolhead, Clara; Macready, Anna L; Fallaize, Rosalind; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Kolossa, Silvia; Hartwig, Kai; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Daly, E J; Akujobi, Victor; O'Riordan, Rick; Hoonhout, Jettie; Claassen, Arjan; Hoeller, Ulrich; Gundersen, Thomas E; Kaland, Siv E; Matthews, John N S; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Alfredo Martinez, J; Saris, Wim H M; Daniel, Hannelore; Gibney, Mike; Mathers, John C

2015-01-01

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

Study design and methodology for a multicentre, randomised controlled trial of transcranial direct current stimulation as a treatment for unipolar and bipolar depression.

PubMed

Alonzo, Angelo; Aaronson, Scott; Bikson, Marom; Husain, Mustafa; Lisanby, Sarah; Martin, Donel; McClintock, Shawn M; McDonald, William M; O'Reardon, John; Esmailpoor, Zeinab; Loo, Colleen

2016-11-01

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5mA, 20 sessions of 30min duration over 4weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. Copyright © 2016 Elsevier Inc. All rights reserved.

Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis.

PubMed

Fysh, Edward T H; Thomas, Rajesh; Read, Catherine A; Kwan, Ben C H; Lam, Ben C H; Yap, Elaine; Horwood, Fiona C; Lee, Pyng; Piccolo, Francesco; Shrestha, Ranjan; Garske, Luke A; Lam, David C L; Rosenstengel, Andrew; Bint, Michael; Murray, Kevin; Smith, Nicola A; Lee, Y C Gary

2014-11-06

Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients' remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. Australia New Zealand Clinical Trials Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121. 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.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

PubMed

Roulaud, M; Durand-Zaleski, I; Ingrand, P; Serrie, A; Diallo, B; Peruzzi, P; Hieu, P D; Voirin, J; Raoul, S; Page, P; Fontaine, D; Lantéri-Minet, M; Blond, S; Buisset, N; Cuny, E; Cadenne, M; Caire, F; Ranoux, D; Mertens, P; Naous, H; Simon, E; Emery, E; Gadan, B; Regis, J; Sol, J-C; Béraud, G; Debiais, F; Durand, G; Guetarni Ging, F; Prévost, A; Brandet, C; Monlezun, O; Delmotte, A; d'Houtaud, S; Bataille, B; Rigoard, P

2015-03-01

Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

PubMed

Eastwood, Glenn M; Schneider, Antoine G; Suzuki, Satoshi; Peck, Leah; Young, Helen; Tanaka, Aiko; Mårtensson, Johan; Warrillow, Stephen; McGuinness, Shay; Parke, Rachael; Gilder, Eileen; Mccarthy, Lianne; Galt, Pauline; Taori, Gopal; Eliott, Suzanne; Lamac, Tammy; Bailey, Michael; Harley, Nerina; Barge, Deborah; Hodgson, Carol L; Morganti-Kossmann, Maria Cristina; Pébay, Alice; Conquest, Alison; Archer, John S; Bernard, Stephen; Stub, Dion; Hart, Graeme K; Bellomo, Rinaldo

2016-07-01

In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31). In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment. Copyright © 2016. Published by Elsevier Ireland Ltd.

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.

A guide to multi-centre ethics for surgical research in Australia and New Zealand.

PubMed

Boult, Maggi; Fitzpatrick, Kate; Maddern, Guy; Fitridge, Robert

2011-03-01

This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax.

PubMed

Brown, Simon G A; Ball, Emma L; Perrin, Kyle; Read, Catherine A; Asha, Stephen E; Beasley, Richard; Egerton-Warburton, Diana; Jones, Peter G; Keijzers, Gerben; Kinnear, Frances B; Kwan, Ben C H; Lee, Y C Gary; Smith, Julian A; Summers, Quentin A; Simpson, Graham

2016-09-13

Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP. This multicentre, prospective, randomised, open label, parallel group, non-inferiority study will randomise 342 participants with a first large PSP to conservative or interventional management. To maintain allocation concealment, randomisation will be performed in real time by computer and stratified by study site. Conservative management will involve a period of observation prior to discharge, with intervention for worsening symptoms or physiological instability. Interventional treatment will involve insertion of a small bore drain. If drainage continues after 1 hour, the patient will be admitted. If drainage stops, the drain will be clamped for 4 hours. The patient will be discharged if the lung remains inflated. Otherwise, the patient will be admitted. The primary end point is the proportion of participants with complete lung re-expansion by 8 weeks. Secondary end points are as follows: days in hospital, persistent air leak, predefined complications and adverse events, time to resolution of symptoms, and pneumothorax recurrence during a follow-up period of at least 1 year. The study has 95% power to detect an absolute non-inferiority margin of 9%, assuming 99% successful expansion at 8 weeks in the invasive treatment arm. The primary analysis will be by intention to treat. Local ethics approval has been obtained for all sites. Study findings will be disseminated by publication in a high-impact international journal and presentation at major international Emergency Medicine and Respiratory meetings. ACTRN12611000184976; 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/

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.

Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation.

PubMed

Bourbeau, Jean; Lavoie, Kim L; Sedeno, Maria; De Sousa, Dorothy; Erzen, Damijan; Hamilton, Alan; Maltais, François; Troosters, Thierry; Leidy, Nancy

2016-04-04

Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study. PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies. The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations. NCT02085161. 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 high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

PubMed

Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W

2016-12-01

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ 2 =0.41; p=0.813) or the 16-weeks complete medication period (χ 2 =0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

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.

Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trial.

PubMed

Goldblatt, David; Southern, Jo; Andrews, Nick J; Burbidge, Polly; Partington, Jo; Roalfe, Lucy; Valente Pinto, Marta; Thalasselis, Vasilli; Plested, Emma; Richardson, Hayley; Snape, Matthew D; Miller, Elizabeth

2018-02-01

Infants in the UK were first offered a pneumococcal conjugate vaccine (PCV7) in 2006, given at 2 and 4 months of age and a booster dose at 13 months (2 + 1 schedule). A 13-valent vaccine (PCV13) replaced PCV7 in 2010. We aimed to compare the post-booster antibody response in UK infants given a reduced priming schedule of PCV13 (ie, a 1 + 1 schedule) versus the current 2 + 1 schedule and to assess the potential effect on population protection. In this multicentre, parallel group, randomised controlled trial, we recuited infants due to receive their primary immunisations aged up to 13 weeks on first vaccinations by information booklets mailed out via the NHS Child Health Information Service and the UK National Health Application and Infrastructure Services. Eligible infants were randomly assigned (1:1) to receive PCV13 at 2, 4, and 12 months (2 + 1 schedule) or 3 and 12 months of age (1 + 1 schedule) delivered with other routine vaccinations. Randomisation was done by computer-generated permuted block randomisation, with a block size of six. Participants and clinical trial staff were not masked to treatment allocation. The primary endpoint was serotype-specific immunoglobulin G concentrations values (geometric mean concentrations [GMC] in μg/mL) measured in blood samples collected at 13 months of age. Analysis was by modified intention to treat with all individuals included by randomised group if they had a laboratory result. This trial is registered on the EudraCT clinical trial database, number 2015-000817-32, and ClinicalTrials.gov, number NCT02482636. Between September, 2015, and June, 2016, 376 infants were assessed for eligibility. 81 infants were excluded for not meeting the inclusion criteria (n=50) or for other reasons (n=31). 213 eligible infants were enrolled and randomly allocated to group 1 (n=106; 2 + 1 schedule) or to group 2 (n=107; 1 + 1 schedule). In group 1, 91 serum samples were available for analysis 1 month after booster immunisation versus 86 in group 2. At month 13, post-booster, GMCs were equivalent between schedules for serotypes 3 (0·61 μg/mL in group 1 vs 0·62 μg/mL in group 2), 5 (1·74 μg/mL vs 2·11 μg/mL), 7F (3·98 μg/mL vs 3·36 μg/mL), 9V (2·34 μg/mL vs 2·50 μg/mL), and 19A (8·38 μg/mL vs 8·83 μg/mL). Infants given the 1 + 1 schedule had significantly greater immunogenicity post-booster than those given the 2 + 1 schedule for serotypes 1 (8·92 μg/mL vs 3·07 μg/mL), 4 (3·43 μg/mL vs 2·55 μg/mL), 14 (16·9 μg/mL vs 10·49 μg/mL), and 19F (14·76 μg/mL vs 11·12 μg/mL; adjusted p value range <0·001 to 0·047). The 2 + 1 schedule was superior for serotypes 6A, 6B, 18C and 23F (adjusted p value range <0·0001 to 0·017). In a predefined numerical subset of all of the infants recruited to the study (n=40 [20%]), functional serotype-specific antibody was similar between schedules. 26 serious adverse events were recorded in 21 (10%) infants across the study period; 18 (n=13) were in the 2 + 1 group and eight (n=8) in the 1 + 1 group. Only one serious adverse event, a high temperature and refusal to feed after the first vaccination visit in a child on the 2+1 schedule was considered related to vaccine. Our findings show that for nine of the 13 serotypes in PCV13, post-booster responses in infants primed with a single dose are equivalent or superior to those seen following the standard UK 2 + 1 schedule. Introducing a 1 + 1 schedule in countries with a mature PCV programme and established herd immunity is likely to maintain population control of vaccine-type pneumococcal disease. NIHR and the Bill & Melinda Gates 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.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review.

PubMed

Díaz-Delgado, Josué; Pool, Roy; Hoppes, Sharman; Cerezo, Argine; Quesada-Canales, Óscar; Stoica, George

2017-05-18

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

Multicentre study of fragrance allergy in Hungary. Immediate and late type reactions.

PubMed

Temesvári, Erzsébet; Németh, Ilona; Baló-Banga, Mátyás J; Husz, Sándor; Kohánka, Valéria; Somos, Zsuzsa; Judák, Rita; Remenyik, E V A; Szegedi, Andrea; Nebenführer, László; Mészáros, Csilla; Horváth, Attila

2002-06-01

The authors followed the frequency of fragrance contact sensitization in Hungary in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were tested with fragrance mix (FM), and positive reactions were observed in 294 (8.2%). In 160 FM hypersensitive patients, the study was continued with patch testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol, amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss absolute). Of the patients tested, 70.6% produced positive reactions to the constituents. FM contact sensitization was mainly observed in female patients (74.4%). The incidence of contact urticaria in FM hypersensitive patients was 6.1%. Simultaneous patch test trials of other environmental contact allergens, in both early and late evaluations, mainly confirmed hypersensitivity reactions to balsams. Female dominance of hypersensitivity reactions observed during testing the individual components of the mix was striking (82.4%). In positive skin reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most frequently. We also tested the 104 patients who produced negative reactions to FM with the constituent individual allergens, with 11.9% positive incidence. The clinical symptoms of the patients were above all manifest in the form of contact eczema, located on the hands, face, eyelids and axillae. With this study, the authors, members of the Hungarian Contact Dermatitis Research Group, call attention to one of the most frequent allergens in the environment.

'Away Days' in multi-centre randomised controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment.

PubMed

Jefferson, Laura; Cook, Liz; Keding, Ada; Brealey, Stephen; Handoll, Helen; Rangan, Amar

2015-11-06

'Away Days' (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multi-centre randomised controlled trials (RCTs). We explored the use of Away Days in multi-centre RCTs and analysed the effect on patient recruitment in a case study. Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multi-centre pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. A total of 94 people responded to the survey. The majority (78%), who confirmed had organised an Away Day previously, found them to be useful. This is despite their costs.. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multi-centre surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate.

PubMed

Downey, Darragh; Dutta, Arpan; McKie, Shane; Dawson, Gerard R; Dourish, Colin T; Craig, Kevin; Smith, Mark A; McCarthy, Dennis J; Harmer, Catherine J; Goodwin, Guy M; Williams, Steve; Deakin, J F William

2016-06-01

Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan. Both ketamine and lanicemine gradually increased the blood oxygen level dependent signal in sgACC and rostral ACC as the primary outcome measure. No decreases in signal were seen in any region. Interviewer-rated psychotic and dissociative symptoms were minimal following administration of lanicemine. There was no significant antidepressant effect of either infusion compared to saline. The previously reported deactivation of sgACC after ketamine probably reflects the rapid and pronounced subjective effects evoked by the bolus-infusion method used in the previous study. Activation of the ACC was observed following two different NMDA compounds in both Manchester and Oxford using different 3T MRI scanners, and this effect predicted improvement in mood 1 and 7 days post-infusion. These findings suggest that the initial site of antidepressant action for NMDA antagonists may be the ACC (NCT01046630. A Phase I, Multi-centre, Double-blind, Placebo-controlled Parallel Group Study to Assess the pharmacoMRI Effects of AZD6765 in Male and Female Subjects Fulfilling the Criteria for Major Depressive Disorder; http://clinicaltrials.gov/show/NCT01046630). Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Comparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patients.

PubMed

Bachert, C; Kuna, P; Sanquer, F; Ivan, P; Dimitrov, V; Gorina, M M; van de Heyning, P; Loureiro, A

2009-01-01

Bilastine is a novel, nonsedating H(1)-antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR). This randomized, double blind, placebo-controlled, parallel-group multicentre study evaluated the effect of 2 weeks' treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12-70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period. Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis-associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%). Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms.

The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

PubMed

Cockayne, E Sarah

2010-02-08

Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. Current Controlled Trials ISRCTN18994246.

Efficacy and Safety of Secukinumab in Elderly Subjects with Moderate to Severe Plaque Psoriasis: A Pooled Analysis of Phase III Studies.

PubMed

Körber, Andreas; Papavassilis, Charis; Bhosekar, Vaishali; Reinhardt, Maximilian

2018-02-01

Psoriasis is a chronic inflammatory skin disease, affecting patients of a wide age range, including elderly patients. Elderly patients can respond differently to drug treatments and can be more vulnerable to adverse reactions. There are limited data on biologic therapies for psoriasis in elderly subjects. Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has proven significant efficacy in the treatment of moderate to severe psoriasis. A post-hoc analysis of three phase III trials (ERASURE, FIXTURE and CLEAR) was performed to evaluate the efficacy and safety of secukinumab in elderly subjects. Studies were multicentre, randomized, parallel-group, double-blind, 52-week phase III trials in subjects with moderate to severe plaque psoriasis. For efficacy analyses, 67 elderly subjects (≥ 65 years) treated with secukinumab 300 mg were compared with 841 younger subjects (18-64 years). Psoriasis Area and Severity Index (PASI), Dermatological Life Quality Index (DLQI) and safety were analysed. Elderly subjects had higher baseline frequencies of cardiovascular and metabolic disorders. Secukinumab efficacy in elderly subjects was comparable to that in younger subjects throughout 52 weeks of treatment. PASI 75 response was reached by 81.8% of elderly subjects and 79.4% of younger subjects at Week 52. Similar rates of DLQI 0/1 response were observed. The total rate of adverse events was similar between elderly and younger subjects. Secukinumab at the recommended dose (300 mg) is effective and acceptably safe in subjects aged ≥ 65 years with moderate to severe psoriasis, with quality-of-life benefits, despite an increased prevalence of cardiovascular and metabolic comorbidities in this population.

Successful recruitment to trials: findings from the SCIMITAR+ Trial.

PubMed

Peckham, Emily; Arundel, Catherine; Bailey, Della; Callen, Tracy; Cusack, Christina; Crosland, Suzanne; Foster, Penny; Herlihy, Hannah; Hope, James; Ker, Suzy; McCloud, Tayla; Romain-Hooper, Crystal-Bella; Stribling, Alison; Phiri, Peter; Tait, Ellen; Gilbody, Simon

2018-01-19

Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment.

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

PubMed Central

Luján-Sanchis, Marisol; Pérez-Cuadrado-Robles, Enrique; García-Lledó, Javier; Juanmartiñena Fernández, José-Francisco; Elli, Luca; Jiménez-García, Victoria-Alejandra; Egea-Valenzuela, Juan; Valle-Muñoz, Julio; Carretero-Ribón, Cristina; Fernández-Urién-Sainz, Ignacio; López-Higueras, Antonio; Alonso-Lázaro, Noelia; Sanjuan-Acosta, Mileidis; Sánchez-Ceballos, Francisco; Rosa, Bruno; González-Vázquez, Santiago; Branchi, Federica; Ruano-Díaz, Lucía; Prieto-de-Frías, César; Pons-Beltrán, Vicente; Borque-Barrera, Pilar; González-Suárez, Begoña; Xavier, Sofía; Argüelles-Arias, Federico; Herrerías-Gutiérrez, Juan-Manuel; Pérez-Cuadrado-Martínez, Enrique; Sempere-García-Argüelles, Javier

2017-01-01

AIM To analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE). METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed. RESULTS The overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD. CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD. PMID:28216978

Design of an international multicentre RCT on group schema therapy for borderline personality disorder.

PubMed

Wetzelaer, Pim; Farrell, Joan; Evers, Silvia M A A; Jacob, Gitta A; Lee, Christopher W; Brand, Odette; van Breukelen, Gerard; Fassbinder, Eva; Fretwell, Heather; Harper, R Patrick; Lavender, Anna; Lockwood, George; Malogiannis, Ioannis A; Schweiger, Ulrich; Startup, Helen; Stevenson, Teresa; Zarbock, Gerhard; Arntz, Arnoud

2014-11-18

Borderline personality disorder (BPD) is a severe and highly prevalent mental disorder. Schema therapy (ST) has been found effective in the treatment of BPD and is commonly delivered through an individual format. A group format (group schema therapy, GST) has also been developed. GST has been found to speed up and amplify the treatment effects found for individual ST. Delivery in a group format may lead to improved cost-effectiveness. An important question is how GST compares to treatment as usual (TAU) and what format for delivery of schema therapy (format A; intensive group therapy only, or format B; a combination of group and individual therapy) produces the best outcomes. An international, multicentre randomized controlled trial (RCT) will be conducted with a minimum of fourteen participating centres. Each centre will recruit multiple cohorts of at least sixteen patients. GST formats as well as the orders in which they are delivered to successive cohorts will be balanced. Within countries that contribute an uneven number of sites, the orders of GST formats will be balanced within a difference of one. The RCT is designed to include a minimum of 448 patients with BPD. The primary clinical outcome measure will be BPD severity. Secondary clinical outcome measures will include measures of BPD and general psychiatric symptoms, schemas and schema modes, social functioning and quality of life. Furthermore, an economic evaluation that consists of cost-effectiveness and cost-utility analyses will be performed using a societal perspective. Lastly, additional investigations will be carried out that include an assessment of the integrity of GST, a qualitative study on patients' and therapists' experiences with GST, and studies on variables that might influence the effectiveness of GST. This trial will compare GST to TAU for patients with BPD as well as two different formats for the delivery of GST. By combining an evaluation of clinical effectiveness, an economic evaluation and additional investigations, it will contribute to an evidence-based understanding of which treatment should be offered to patients with BPD from clinical, economic, and stakeholders' perspectives. Netherlands Trial Register NTR2392. Registered 25 June 2010.

Study protocol of the CAREST-trial: a randomised controlled trial on the (cost-) effectiveness of a CBT-based online self-help training for fear of cancer recurrence in women with curatively treated breast cancer.

PubMed

van Helmondt, Sanne Jasperine; van der Lee, Marije Liesbeth; de Vries, Jolanda

2016-07-25

One of the most prevalent long-term consequences of surviving breast cancer is fear of cancer recurrence (FCR), which is associated with higher (mental) healthcare costs and lower surveillance rates. The majority of breast cancer survivors report a need for professional help in dealing with FCR. An easy-accessible and cost-effective evidence-based psychological intervention for reducing FCR is lacking. In the current study an online self-help training to reduce FCR will be evaluated. In addition, the secondary aim of this study is to identify factors that predict whether women can benefit from the online self-help training or not. A multi-centre, parallel-groups, randomised controlled trial will be conducted to evaluate the (cost-) effectiveness of the CAREST-trial. A sample of 454 women with curatively treated breast cancer will be recruited from 8 hospitals in the Netherlands. Participants will be randomised to the intervention or usual care group (1:1). Self-report measures will be completed at baseline, 3 (post-intervention), 9, and 24 months. Primary outcome is FCR severity; secondary outcomes are healthcare costs, health status, and psychological distress. The online tailored self-help training "Less fear after cancer" is based on cognitive behavioural therapy and consists of 2 basic modules (psycho-education; basic principles of cognitive behavioural therapy) and 4 optional modules (rumination; action; relaxation; reassurance) to choose from. Each module consists of an informative part (texts, videos, audio files) and a practical part (exercises). For every patient, the intervention will be available for three months. Personal online support by an e-mail coach is available. Online self-help training may be an easy-accessible and cost-effective treatment to reduce the impact of FCR at an early stage in a large group of breast cancer survivors. A strength is the 24 months follow-up period in the health economic evaluation. The results of the study will provide information on the possible strengths and benefits of online self-help training for FCR in breast cancer survivors. This study is registered at the Netherlands Trial Register ( NTR4119 , date registered: August 15, 2013).

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.

Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD.

PubMed

Kilfeather, S A; Ponitz, H H; Beck, E; Schmidt, P; Lee, A; Bowen, I; Hesse, Ch

2004-05-01

We performed a multicentre, randomised, double-blind (within-device), placebo- and active-controlled, parallel-group study to compare the efficacy and safety of ipratropium bromide plus fenoterol hydrobromide (IB/FEN; Berodual) delivered via the novel, propellant-free Respimat Soft Mist Inhaler (SMI) and from a chlorofluorocarbon (CFC)-metered-dose inhaler (MDI) in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. After 2-weeks' run-in (CFC-MDI [IB 20 microg/FEN 50 microg per actuation] two actuations q.i.d. [MDI 40/100]), 892 patients were randomised to Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB 20 microg/FEN 50 microg (Respimat SMI 20/50) or placebo (one actuation q.i.d.), or a CFC-MDI containing IB 20 microg/FEN 50 microg (MDI 40/100) or placebo (two actuations q.i.d.) for 12 weeks. Analysis of the primary endpoint (change in forced expiratory volume in 1 s [FEV1] in the first 60 min after dosing [area under the curve; AUC0-1h]) on day 85 showed that the efficacy of Respimat SMI 20/50 (but not Respimat SMI 10/25) was not inferior to that of MDI 40/100. The safety profile of Respimat SMI was comparable to CFC-MDI. Switching from MDI 40/100 to Respimat SMI was well tolerated. Respimat SMI enables a 50% reduction of the nominal inhaled dose of IB/FEN in COPD patients while offering similar therapeutic efficacy and safety to the CFC-MDI.

Mathematical Abstraction: Constructing Concept of Parallel Coordinates

NASA Astrophysics Data System (ADS)

Nurhasanah, F.; Kusumah, Y. S.; Sabandar, J.; Suryadi, D.

2017-09-01

Mathematical abstraction is an important process in teaching and learning mathematics so pre-service mathematics teachers need to understand and experience this process. One of the theoretical-methodological frameworks for studying this process is Abstraction in Context (AiC). Based on this framework, abstraction process comprises of observable epistemic actions, Recognition, Building-With, Construction, and Consolidation called as RBC + C model. This study investigates and analyzes how pre-service mathematics teachers constructed and consolidated concept of Parallel Coordinates in a group discussion. It uses AiC framework for analyzing mathematical abstraction of a group of pre-service teachers consisted of four students in learning Parallel Coordinates concepts. The data were collected through video recording, students’ worksheet, test, and field notes. The result shows that the students’ prior knowledge related to concept of the Cartesian coordinate has significant role in the process of constructing Parallel Coordinates concept as a new knowledge. The consolidation process is influenced by the social interaction between group members. The abstraction process taken place in this group were dominated by empirical abstraction that emphasizes on the aspect of identifying characteristic of manipulated or imagined object during the process of recognizing and building-with.

The talent study: a multicentre randomized controlled trial assessing the impact of a 'tailored lifestyle self-management intervention' (talent) on weight reduction.

PubMed

Melchart, Dieter; Doerfler, Wolfgang; Eustachi, Axel; Wellenhofer-Li, Yanqing; Weidenhammer, Wolfgang

2015-01-01

Overweight is considered an important risk factor for diseases in the context of metabolic syndrome. Lifestyle modifications are the means of choice to reduce weight in persons with a Body Mass Index of 28 to 35. The study examines whether there are any differences between two intervention strategies regarding weight reduction in overweight persons. The study is a multicentre randomized controlled trial with observation duration of 12 months. Eight study centres are involved to include a minimal sample size of 150 participants. Randomization ratio is 2:1. Feasible persons are checked according to inclusion and exclusion criteria and after given informed consent are assigned randomly to one of two intervention programs: A) intervention group: comprehensive lifestyle modification program (Individual Health Management IHM) with 3 months reduction phase plus 9 months maintaining phase, B) control group: written information with advice for healthy food habits (Usual care UC). Participants of the IHM group have access to a web-based health portal and join 3 full-day and 10 two-hour training sessions during the first 3 months. During the remaining 9 months four refresh trainings will be performed. There are 3 different diet strategies (fasting, two-day diet, meal replacement) for free choice. Participants of the control group are provided with acknowledged rules for healthy food according to the German Nutrition Society (DGE). Examinations are conducted at baseline, after 3, 6, 9 and 12 months. They include body weight, waist circumference, blood pressure, laboratory findings and a bio-impedance analysis to measure body composition. Statistical analysis of the primary outcome 'change of body weight after 12 months' is based on ITT population including analysis of variance of the weight differences between month 0 and 12 with the factors 'group', 'baseline value' and 'study centre'. Secondary outcomes will be analyzed exploratively. The monitoring of the study will implement different measures to enhance compliance, avoid attrition and ensure data quality. Based on a blended learning concept and using web-based e-health tools the program promises to achieve sustainable effects in weight reduction. German Clinical Trials Register Freiburg (DRKS): DRKS00006736 (date registered 20/09/2014).

Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial.

PubMed

Doig, Gordon S; Simpson, Fiona; Heighes, Philippa T; Bellomo, Rinaldo; Chesher, Douglas; Caterson, Ian D; Reade, Michael C; Harrigan, Peter W J

2015-12-01

Equipoise exists regarding the benefits of restricting caloric intake during electrolyte replacement for refeeding syndrome, with half of intensive care specialists choosing to continue normal caloric intake. We aimed to assess whether energy restriction affects the duration of critical illness, and other measures of morbidity, compared with standard care. We did a randomised, multicentre, single-blind clinical trial in 13 hospital intensive care units (ICUs) in Australia (11 sites) and New Zealand (two sites). Adult critically ill patients who developed refeeding syndrome within 72 h of commencing nutritional support in the ICU were enrolled and allocated to receive continued standard nutritional support or protocolised caloric restriction. 1:1 computer-based randomisation was done in blocks of variable size, stratified by enrolment serum phosphate concentration (>0·32 mmol/L vs ≤0·32 mmol/L) and body-mass index (BMI; >18 kg/m(2)vs ≤18 kg/m(2)). The primary outcome was the number of days alive after ICU discharge, with 60 day follow-up, in a modified intention-to-treat population of all randomly allocated patients except those mistakenly enrolled. Days alive after ICU discharge was a composite outcome based on ICU length of stay, overall survival time, and mortality. The Refeeding Syndrome Trial was registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR number 12609001043224). Between Dec 3, 2010, and Aug 13, 2014, we enrolled 339 adult critically ill patients: 170 were randomly allocated to continued standard nutritional support and 169 to protocolised caloric restriction. During the 60 day follow-up, the mean number of days alive after ICU discharge in 165 assessable patients in the standard care group was 39·9 (95% CI 36·4-43·7) compared with 44·8 (95% CI 40·9-49·1) in 166 assessable patients in the caloric restriction group (difference 4·9 days, 95% CI -2·3 to 13·6, p=0·19). Nevertheless, protocolised caloric restriction improved key individual components of the primary outcome: more patients were alive at day 60 (128 [78%] of 163 vs 149 [91%] of 164, p=0·002) and overall survival time was increased (48·9 [SD 1·46] days vs 53·65 [0·97] days, log-rank p=0·002). Protocolised caloric restriction is a suitable therapeutic option for critically ill adults who develop refeeding syndrome. We did not identify any safety concerns associated with the use of protocolised caloric restriction. National Health and Medical Research Council of Australia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long-chain omega-3 fatty acids in aneurysmal subarachnoid hemorrhage: A randomized pilot trial of pharmaconutrition.

PubMed

Saito, Geisi; Zapata, Rodrigo; Rivera, Rodrigo; Zambrano, Héctor; Rojas, David; Acevedo, Hernán; Ravera, Franco; Mosquera, John; Vásquez, Juan E; Mura, Jorge

2017-01-01

Functional recovery after aneurysmal subarachnoid hemorrhage (SAH) remains a significant problem. We tested a novel therapeutic approach with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) to assess the safety and feasibility of an effectiveness trial. We conducted a multicentre, parallel, randomized, open-label pilot trial. Patients admitted within 72 hours after SAH with modified Fisher scale scores of 3 or 4 who were selected for scheduled aneurysm clipping were allocated to receive either n-3 PUFA treatment (parenteral perioperative: 5 days; oral: 8 weeks) plus usual care or usual care alone. Exploratory outcome measures included major postoperative intracranial bleeding complications (PIBCs), cerebral infarction caused by delayed cerebral ischemia, shunt-dependent hydrocephalus, and consent rate. The computed tomography evaluator was blinded to the group assignment. Forty-one patients were randomized, but one patient had to be excluded after allocation. Twenty patients remained for intention to treat analysis in each trial arm. No PIBs (95% confidence interval [CI]: 0.00 to 0.16) or other unexpected harm were observed in the intervention group (IG). No patient suspended the intervention due to side effects. There was a trend towards improvements in all benefit-related outcomes in the IG. The overall consent rate was 0.91 (95% CI: 0.78 to 0.96), and there was no consent withdrawal. Although the balance between the benefit and harm of the intervention appears highly favourable, further testing on SAH patients is required. We recommend proceeding with amendments in a dose-finding trial to determine the optimal duration of parenteral treatment.

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

PubMed Central

Croall, Iain D.; Lohner, Valerie; Moynihan, Barry; Khan, Usman; Hassan, Ahamad; O’Brien, John T.; Morris, Robin G.; Tozer, Daniel J.; Cambridge, Victoria C.; Harkness, Kirsty; Werring, David J.; Blamire, Andrew M.; Ford, Gary A.; Barrick, Thomas R.

2017-01-01

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies. PMID:28487471

Rates of self-harm presenting to general hospitals: a comparison of data from the Multicentre Study of Self-Harm in England and Hospital Episode Statistics

PubMed Central

Turnbull, Pauline; Hawton, Keith; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Townsend, Ellen; Khundakar, Kazem; Kapur, Nav

2016-01-01

Objective Rates of hospital presentation for self-harm in England were compared using different national and local data sources. Design The study was descriptive and compared bespoke data collection methods for recording self-harm presentations to hospital with routinely collected hospital data. Setting Local area data on self-harm from the 3 centres of the Multicentre Study of Self-harm in England (Oxford, Manchester and Derby) were used along with national and local routinely collected data on self-harm admissions and emergency department attendances from Hospital Episode Statistics (HES). Primary outcome Rate ratios were calculated to compare rates of self-harm generated using different data sources nationally and locally (between 2010 and 2012) and rates of hospital presentations for self-harm were plotted over time (between 2003 and 2012), based on different data sources. Results The total number of self-harm episodes between 2010 and 2012 was 13 547 based on Multicentre Study data, 9600 based on HES emergency department data and 8096 based on HES admission data. Nationally, routine HES data underestimated overall rates of self-harm by approximately 60% compared with rates based on Multicentre Study data (rate ratio for HES emergency department data, 0.41 (95% CI 0.35 to 0.49); rate ratio for HES admission data, 0.42 (95% CI 0.36 to 0.49)). Direct local area comparisons confirmed an overall underascertainment in the HES data, although the difference varied between centres. There was a general increase in self-harm over time according to HES data which contrasted with a fall and then a rise in the Multicentre Study data. Conclusions There was a consistent underestimation of presentations for self-harm recorded by HES emergency department data, and fluctuations in year-on-year figures. HES admission data appeared more reliable but missed non-admitted episodes. Routinely collected data may miss important trends in self-harm and cannot be used in isolation as the basis for a robust national indicator of self-harm. PMID:26883238

Generalisation and extension of a web-based data collection system for clinical studies using Java and CORBA.

PubMed

Eich, H P; Ohmann, C

1999-01-01

Inadequate informatical support of multi-centre clinical trials lead to pure quality. In order to support a multi-centre clinical trial a data collection via WWW and Internet based on Java has been developed. In this study a generalization and extension of this prototype has been performed. The prototype has been applied to another clinical trial and a knowledge server based on C+t has been integrated via CORBA. The investigation and implementation of security aspects of web-based data collection is now under evaluation.

Cross-over studies underestimate energy compensation: The example of sucrose-versus sucralose-containing drinks.

PubMed

Gadah, Nouf S; Brunstrom, Jeffrey M; Rogers, Peter J

2016-12-01

The vast majority of preload-test-meal studies that have investigated the effects on energy intake of disguised nutrient or other food/drink ingredient manipulations have used a cross-over design. We argue that this design may underestimate the effect of the manipulation due to carry-over effects. To test this we conducted comparable cross-over (n = 69) and parallel-groups (n = 48) studies testing the effects of sucrose versus low-calorie sweetener (sucralose) in a drink preload on test-meal energy intake. The parallel-groups study included a baseline day in which only the test meal was consumed. Energy intake in that meal was used to control for individual differences in energy intake in the analysis of the effects of sucrose versus sucralose on energy intake on the test day. Consistent with our prediction, the effect of consuming sucrose on subsequent energy intake was greater when measured in the parallel-groups study than in the cross-over study (respectively 64% versus 36% compensation for the 162 kcal difference in energy content of the sucrose and sucralose drinks). We also included a water comparison group in the parallel-groups study (n = 24) and found that test-meal energy intake did not differ significantly between the water and sucralose conditions. Together, these results confirm that consumption of sucrose in a drink reduces subsequent energy intake, but by less than the energy content of the drink, whilst drink sweetness does not increase food energy intake. Crucially, though, the studies demonstrate that study design affects estimated energy compensation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial.

PubMed

van Vliet, Elvira O G; Nijman, Tobias A J; Schuit, Ewoud; Heida, Karst Y; Opmeer, Brent C; Kok, Marjolein; Gyselaers, Wilfried; Porath, Martina M; Woiski, Mallory; Bax, Caroline J; Bloemenkamp, Kitty W M; Scheepers, Hubertina C J; Jacquemyn, Yves; Beek, Erik van; Duvekot, Johannes J; Franssen, Maureen T M; Papatsonis, Dimitri N; Kok, Joke H; van der Post, Joris A M; Franx, Arie; Mol, Ben W; Oudijk, Martijn A

2016-05-21

In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947. Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0·91, 95% CI 0·61-1·37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2·20, 95% CI 0·91-5·33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups. In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes. ZonMw (the Netherlands Organisation for Health Research and Development). Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

[Effects of Behaviour-oriented Exercise Interventions as Supplement within Structured Health-care Programmes for Diabetes Mellitus Type 2 - A Quasi-experimental Multicentre Intervention Study].

PubMed

Eckert, K; Lange, M

2016-06-01

Exercise programs do not belong to standard treatment within disease management programmes for diabetes mellitus type 2, up to now. For these reason the effects of a 10-week behaviour-oriented exercise programme have been evaluated focusing on change in activity behaviour and health-related qualitiy of life. 202 patients took part in the investigation. There were significant inbetween group differences in some aspects of the outcome parameters. The study presents useful information on how to modify existing DMPs successfully for improving patient treatment. © Georg Thieme Verlag KG Stuttgart · New York.

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care.

PubMed

Ramnarayan, Padmanabhan; Lister, Paula; Dominguez, Troy; Habibi, Parviz; Edmonds, Naomi; Canter, Ruth R; Wulff, Jerome; Harrison, David A; Mouncey, Paul M; Peters, Mark J

2018-06-04

Although high-flow nasal cannula therapy (HFNC) has become a popular mode of non-invasive respiratory support (NRS) in critically ill children, there are no randomised controlled trials (RCTs) comparing it with continuous positive airway pressure (CPAP). We performed a pilot RCT to explore the feasibility, and inform the design and conduct, of a future large pragmatic RCT comparing HFNC and CPAP in paediatric critical care. In this multi-centre pilot RCT, eligible patients were recruited to either Group A (step-up NRS) or Group B (step-down NRS). Participants were randomised (1:1) using sealed opaque envelopes to either CPAP or HFNC as their first-line mode of NRS. Consent was sought after randomisation in emergency situations. The primary study outcomes were related to feasibility (number of eligible patients in each group, proportion of eligible patients randomised, consent rate, and measures of adherence to study algorithms). Data were collected on safety and a range of patient outcomes in order to inform the choice of a primary outcome measure for the future RCT. Overall, 121/254 eligible patients (47.6%) were randomised (Group A 60%, Group B 44.2%) over a 10-month period (recruitment rate for Group A, 1 patient/site/month; Group B, 2.8 patients/site/month). In Group A, consent was obtained in 29/33 parents/guardians approached (87.9%), while in Group B 84/118 consented (71.2%). Intention-to-treat analysis included 113 patients (HFNC 59, CPAP 54). Most reported adverse events were mild/moderate (HFNC 8/59, CPAP 9/54). More patients switched treatment from HFNC to CPAP (Group A: 7/16, 44%; Group B: 9/43, 21%) than from CPAP to HFNC (Group A: 3/13, 23%; Group B: 5/41, 12%). Intubation occurred within 72 h in 15/59 (25.4%) of HFNC patients and 10/54 (18.5%) of CPAP patients (p = 0.38). HFNC patients experienced fewer ventilator-free days at day 28 (Group A: 19.6 vs. 23.5; Group B: 21.8 vs. 22.2). Our pilot trial confirms that, following minor changes to consent procedures and treatment algorithms, it is feasible to conduct a large national RCT of non-invasive respiratory support in the paediatric critical care setting in both step-up and step-down NRS patients. clinicaltrials.gov, NCT02612415 . Registered on 23 November 2015.

Narrative exposure therapy for immigrant children traumatized by war: study protocol for a randomized controlled trial of effectiveness and mechanisms of change.

PubMed

Kangaslampi, Samuli; Garoff, Ferdinand; Peltonen, Kirsi

2015-06-17

Millions of children worldwide suffer from posttraumatic stress disorder (PTSD) symptoms and other mental health problems due to repeated exposure to war or organized violence. Forms of cognitive-behavioral therapy (CBT) are the most commonly used treatment for PTSD and appear to be effective for children as well, but little is known about the mechanisms of change through which they achieve their effectiveness. Here we present the study protocol of a randomized controlled trial (RCT) studying the effectiveness and mechanisms of change of Narrative Exposure Therapy (NET), a CBT-based, manualized, short-term intervention for PTSD symptoms resulting from repeated traumatization, in immigrant children traumatized by war. We are conducting a multicentre, pragmatic RCT in a usual care setting. Up to 80 9-17-year-old immigrant children who have experienced war and suffer from PTSD symptoms will be randomized into intervention (NET) and control (treatment as usual, TAU) groups of equal sizes. The effectiveness of NET treatment will be compared to both a waiting list and the parallel TAU positive control group, on the primary outcomes of PTSD and depressive symptoms, psychological distress, resilience, and level of cognitive performance. The effects of the intervention on traumatic memories and posttraumatic cognitions will be studied as potential mechanisms of change mediating overall treatment effectiveness. The possible moderating effects of peritraumatic dissociation, level of cognitive performance, and gender on treatment effectiveness will also be considered. We hypothesize that NET will be more effective than a waitlist condition or TAU in reducing PTSD and other symptoms and improving resilience, and that these effects will be mediated by changes in traumatic memories and posttraumatic cognitions. The results of this trial will provide evidence for the effectiveness of NET in treating trauma-related symptoms in immigrant children affected by war. The trial will also generate insights into the complex relationships between PTSD, memory functions, posttraumatic cognitions and cognitive performance in children, and help guide the future development and implementation of therapeutic interventions for PTSD in children. ClinicalTrials.gov NCT02425280 . Registered 15 April 2015.

A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

PubMed

Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

2011-01-01

Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

Clinical predictors of rectal lymphogranuloma venereum infection: results from a multicentre case-control study in the U.K.

PubMed

Pallawela, S N S; Sullivan, A K; Macdonald, N; French, P; White, J; Dean, G; Smith, A; Winter, A J; Mandalia, S; Alexander, S; Ison, C; Ward, H

2014-06-01

Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present with proctitis, but there are limited data on how to differentiate clinically between LGV and other pathology. We analysed the clinical presentations of rectal LGV in MSM to identify clinical characteristics predictive of LGV proctitis and produced a clinical prediction model. A prospective multicentre case-control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of rectal LGV were compared with controls with rectal symptoms but without LGV. Data from 98 LGV cases and 81 controls were collected from patients and clinicians using computer-assisted self-interviews and clinical report forms. Univariate and multivariate logistic regression was used to compare symptoms and signs. Clinical prediction models for LGV were compared using receiver operating curves. Tenesmus, constipation, anal discharge and weight loss were significantly more common in cases than controls. In multivariate analysis, tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to 8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI 2.71 to 17.92). The best clinical prediction was having one or more of tenesmus, constipation and exudate on proctoscopy, with a sensitivity of 77% and specificity of 65%. This study indicates that tenesmus alone or in combination with constipation makes a diagnosis of LGV in MSM presenting with rectal symptoms more likely. 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 pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

PubMed Central

2011-01-01

Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

Tumour stage and gender predict recurrence and second primary malignancies in head and neck cancer: a multicentre study within the INHANCE consortium.

PubMed

Leoncini, Emanuele; Vukovic, Vladimir; Cadoni, Gabriella; Giraldi, Luca; Pastorino, Roberta; Arzani, Dario; Petrelli, Livia; Wünsch-Filho, Victor; Toporcov, Tatiana Natasha; Moyses, Raquel Ayub; Matsuo, Keitaro; Bosetti, Cristina; La Vecchia, Carlo; Serraino, Diego; Simonato, Lorenzo; Merletti, Franco; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Boccia, Stefania

2018-05-19

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

PubMed

Häussinger, K; Becker, H; Stanzel, F; Kreuzer, A; Schmidt, B; Strausz, J; Cavaliere, S; Herth, F; Kohlhäufl, M; Müller, K-M; Huber, R-M; Pichlmeier, U; Bolliger, Ch T

2005-06-01

The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.

Influence of K-ras status and anti-tumour treatments on complications due to colorectal self-expandable metallic stents: a retrospective multicentre study.

PubMed

Fuccio, Lorenzo; Correale, Loredana; Arezzo, Alberto; Repici, Alessandro; Manes, Gianpiero; Trovato, Cristina; Mangiavillano, Benedetto; Manno, Mauro; Cortelezzi, Claudio Camillo; Dinelli, Marco; Cennamo, Vincenzo; de Bellis, Mario

2014-06-01

This study aimed to explore the relationship between K-ras status, anti-tumour treatments, and the complications of colorectal self-expandable metallic stenting in colorectal cancer. This is a retrospective, multicentre study of 91 patients with obstructive advanced colorectal cancer palliated with enteral stents between 2007 and 2011. K-ras wild-type tumours were diagnosed in 44 patients (48.4%); 82 (90.1%) received chemotherapy and 45 (49.4%) had additional biological therapy (34 bevacizumab, 11 cetuximab). Twenty-one (23.1%) experienced stent-related complications: 11 (52.4%) occurred in the K-ras mutant group (P=0.9). K-ras wild-type patients were not less likely to develop adverse events than K-ras mutant patients (OR, 0.99; 95% CI: 0.4-2.7). Overall mean time to complication was 167.6 days (range 4-720 days), with no difference between the two groups (141 vs. 197 days; P=0.5). Chemotherapy did not influence the risk of complications (OR, 0.56; 95% CI: 0.14-2.9), and there was no evidence that patients treated with chemotherapy and cetuximab were more likely to experience stent-related complications than patients treated with chemotherapy alone, or untreated (OR, 1.2; 95% CI: 0.2-5.9). Although perforation rates were higher with bevacizumab-based treatment (11.8% vs. 7%), this result was not statistically significant (P=0.69). K-ras mutation status, chemotherapy, and biological treatments should not influence colorectal stent-related complication rates. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

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.

Randomised controlled trial of the sliding hip screw versus X-Bolt Dynamic Hip Plating System for the fixation of trochanteric fractures of the hip in adults: a protocol study for WHiTE 4 (WHiTE4).

PubMed

Griffin, Xavier L; Achten, Juul; Sones, William; Cook, Jonathan; Costa, Matthew L

2018-01-26

Sliding hip screw fixation is well established in the treatment of trochanteric fractures of the hip. The X-Bolt Dynamic Hip Plating System builds on the successful design features of the sliding hip screw but differs in the nature of the fixation in the femoral head. A randomised pilot study suggested that the X-bolt Dynamic Hip Plating System might provide similar health-related quality of life while reducing the risk of revision surgery when compared with the sliding hip screw. This is the protocol for a multicentre randomised trial of sliding hip screw versus X-Bolt Dynamic Hip Plating System for patients 60 years and over treated for a trochanteric fracture of the hip. Multicentre, multisurgeon, parallel, two-arm, randomised controlled trial. Patients aged 60 years and older with a trochanteric hip fracture are potentially eligible. Participants will be randomly allocated on a 1:1 basis to either sliding hip screw or X-Bolt Dynamic Hip Plating System. Otherwise, all care will be in accordance with National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in EuroQol-5D health-related quality of life at 4 months postrandomisation. Secondary outcomes include mortality, residential status, revision surgery and radiographic measures. The treatment effect will be estimated using a two-sided t-test adjusted for age, gender and cognitive impairment based on an intention-to-treat analysis. National Research Ethics Committee approved this study on 5 February 2016 (16/WM/0001). The study is sponsored by the University of Oxford and funded through an investigator initiated grant by X-Bolt Orthopaedics. A manuscript for a high-impact peer-reviewed journal will be prepared, and the results will be disseminated to patients through local mechanisms at participating centres. ISRCTN92825709. © 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.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31

PubMed Central

2011-01-01

Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Discussion Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Trial registration Current controlled trials ISRCTN83178718 PMID:21936930

Effects of natural childbirth preparation versus standard antenatal education on epidural rates, experience of childbirth and parental stress in mothers and fathers: a randomised controlled multicentre trial.

PubMed

Bergström, M; Kieler, H; Waldenström, U

2009-08-01

To examine the effects of antenatal education focussing on natural childbirth preparation with psychoprophylactic training versus standard antenatal education on the use of epidural analgesia, experience of childbirth and parental stress in first-time mothers and fathers. Randomised controlled multicentre trial. Fifteen antenatal clinics in Sweden between January 2006 and May 2007. A total of 1087 nulliparous women and 1064 of their partners. Natural group: Antenatal education focussing on natural childbirth preparation with training in breathing and relaxation techniques (psychoprophylaxis). Standard care group: Standard antenatal education focussing on both childbirth and parenthood, without psychoprophylactic training. Both groups: Four 2-hour sessions in groups of 12 participants during third trimester of pregnancy and one follow-up after delivery. Epidural analgesia during labour, experience of childbirth as measured by the Wijma Delivery Experience Questionnaire (B), and parental stress measured by the Swedish Parenthood Stress Questionnaire. The epidural rate was 52% in both groups. There were no statistically significant differences in the experience of childbirth or parental stress between the randomised groups, either in women or men. Seventy percent of the women in the Natural group reported having used psychoprophylaxis during labour. A minority in the Standard care group (37%) had also used this method, but subgroup analysis where these women were excluded did not change the principal findings. Natural childbirth preparation including training in breathing and relaxation did not decrease the use of epidural analgesia during labour, nor did it improve the birth experience or affect parental stress in early parenthood in nulliparous women and men, compared with a standard form of antenatal education.

Effects of natural childbirth preparation versus standard antenatal education on epidural rates, experience of childbirth and parental stress in mothers and fathers: a randomised controlled multicentre trial

PubMed Central

Bergström, M; Kieler, H; Waldenström, U

2009-01-01

Objective To examine the effects of antenatal education focussing on natural childbirth preparation with psychoprophylactic training versus standard antenatal education on the use of epidural analgesia, experience of childbirth and parental stress in first-time mothers and fathers. Design Randomised controlled multicentre trial. Setting Fifteen antenatal clinics in Sweden between January 2006 and May 2007. Sample A total of 1087 nulliparous women and 1064 of their partners. Methods Natural group: Antenatal education focussing on natural childbirth preparation with training in breathing and relaxation techniques (psychoprophylaxis). Standard care group: Standard antenatal education focussing on both childbirth and parenthood, without psychoprophylactic training. Both groups: Four 2-hour sessions in groups of 12 participants during third trimester of pregnancy and one follow-up after delivery. Main outcome measures Epidural analgesia during labour, experience of childbirth as measured by the Wijma Delivery Experience Questionnaire (B), and parental stress measured by the Swedish Parenthood Stress Questionnaire. Results The epidural rate was 52% in both groups. There were no statistically significant differences in the experience of childbirth or parental stress between the randomised groups, either in women or men. Seventy percent of the women in the Natural group reported having used psychoprophylaxis during labour. A minority in the Standard care group (37%) had also used this method, but subgroup analysis where these women were excluded did not change the principal findings. Conclusion Natural childbirth preparation including training in breathing and relaxation did not decrease the use of epidural analgesia during labour, nor did it improve the birth experience or affect parental stress in early parenthood in nulliparous women and men, compared with a standard form of antenatal education. PMID:19538406

Multicentric Evaluation of New Commercial Enzyme Immunoassays for the Detection of Immunoglobulin M and Total Antibodies against Hepatitis A Virus▿

PubMed Central

Arcangeletti, M. C.; Dussaix, E.; Ferraglia, F.; Roque-Afonso, A. M.; Graube, A.; Chezzi, C.

2011-01-01

A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively). PMID:21653739

Cement augmentation of the Proximal Femoral Nail Antirotation (PFNA) - A multicentre randomized controlled trial.

PubMed

Kammerlander, Christian; Hem, Einar S; Klopfer, Tim; Gebhard, Florian; Sermon, An; Dietrich, Michael; Bach, Olaf; Weil, Yoram; Babst, Reto; Blauth, Michael

2018-04-22

New implant designs like the Proximal Femoral Nail Antirotation (PFNA) were developed to reduce failure rates in unstable pertrochanteric fractures in the elderly. Standardized implant augmentation with up to 6 mL of polymethylmethacrylate (PMMA) cement has been introduced to enhance implant anchorage by increasing the implant-bone interface in osteoporotic bone conditions. Biomechanically, loads to failure were significantly higher with augmentation. The primary objective of this study was to compare the mobility of patients with closed unstable trochanteric fractures treated by PFNA either with or without cement augmentation. A prospective multicentre, randomized, patient-blinded trial was conducted with ambulatory patients aged 75 or older who sustained a closed, unstable trochanteric fracture. Surgical fixation had to be performed within 72 h after admission. Outcomes were evaluated at baseline, during surgery, 3 to 14 days after surgery, 3 months, 6 months, and 12 months after surgery. To evaluate the primary objective, patients' walking speed was assessed by the Timed Up and Go (TUG) test. Secondary objectives included the analysis of implant migration assessed on radiographs, quality of life measured by the Barthel Index, mobility measured by the Parker Mobility Score, and complications. Of 253 randomized patients, 223 patients were eligible: 105 patients were allocated to the PFNA Augmentation group and 118 to PFNA group. At 3 to 14 days after surgery, there was no statistical significant difference in mean walking speed between the treatment groups. For the secondary objectives, also no statistical significant differences were found. However, no patient in the PFNA Augmentation group had a reoperation due to mechanical failure or symptomatic implant migration compared to 6 patients in the PFNA group. Augmentation of the PFNA blade did not improve patients' walking ability compared to the use of a non-augmented PFNA but might have the potential to prevent reoperations by strengthening the osteosynthesis construct. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial.

PubMed

Chamberlain Mitchell, Sarah A F; Garrod, Rachel; Clark, Lynne; Douiri, Abdel; Parker, Sean M; Ellis, Jenny; Fowler, Stephen J; Ludlow, Siobhan; Hull, James H; Chung, Kian Fan; Lee, Kai K; Bellas, H; Pandyan, Anand; Birring, Surinder S

2017-02-01

Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. UKCRN ID 10678 and ISRCTN 73039760; 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/.