Randomised crossover trial of telemonitoring in chronic respiratory patients (TeleCRAFT trial)

PubMed Central

Chatwin, M; Hawkins, G; Panicchia, L; Woods, A; Hanak, A; Lucas, R; Baker, E; Ramhamdany, E; Mann, B; Riley, J; Cowie, M R; Simonds, A K

2016-01-01

Objective To assess the impact of home telemonitoring on health service use and quality of life in patients with severe chronic lung disease. Design Randomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring. Participants 68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission. Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team. Outcome measures Primary outcome measure was time to first hospital admission for an acute exacerbation. Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford). Results Median (IQR) number of days to first admission showed no difference between the two groups—77 (114) telemonitoring, 77.5 (61) control (p=0.189). Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026). Home visits increased during telemonitoring; GP consultations were unchanged. Self-efficacy fell, while HAD depression score improved marginally during telemonitoring. Conclusions Telemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients. Trial registration number NCT02180919 (ClinicalTrials.gov). PMID:26962013

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand.

PubMed

Wilder-Smith, Annelies; Byass, Peter; Olanratmanee, Phanthip; Maskhao, Pongsri; Sringernyuang, Luechai; Logan, James G; Lindsay, Steve W; Banks, Sarah; Gubler, Duane; Louis, Valérie R; Tozan, Yesim; Kittayapong, Pattamaporn

2012-11-15

There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7-18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. clinicaltrial.gov. NCT01563640.

Communication interventions to improve adherence to infection control precautions: a randomised crossover trial.

PubMed

Ong, Mei-Sing; Magrabi, Farah; Post, Jeffrey; Morris, Sarah; Westbrook, Johanna; Wobcke, Wayne; Calcroft, Ross; Coiera, Enrico

2013-02-06

Ineffective communication of infection control requirements during transitions of care is a potential cause of non-compliance with infection control precautions by healthcare personnel. In this study, interventions to enhance communication during inpatient transfers between wards and radiology were implemented, in the attempt to improve adherence to precautions during transfers. Two interventions were implemented, comprising (i) a pre-transfer checklist used by radiology porters to confirm a patient's infectious status; (ii) a coloured cue to highlight written infectious status information in the transfer form. The effectiveness of the interventions in promoting adherence to standard precautions by radiology porters when transporting infectious patients was evaluated using a randomised crossover trial at a teaching hospital in Australia. 300 transfers were observed over a period of 4 months. Compliance with infection control precautions in the intervention groups was significantly improved relative to the control group (p < 0.01). Adherence rate in the control group was 38%. Applying the coloured cue resulted in a compliance rate of 73%. The pre-transfer checklist intervention achieved a comparable compliance rate of 71%. When both interventions were applied, a compliance rate of 74% was attained. Acceptability of the coloured cue was high, but adherence to the checklist was low (40%). Simple measures to enhance communication through the provision of a checklist and the use a coloured cue brought about significant improvement in compliance with infection control precautions by transport personnel during inpatient transfers. The study underscores the importance of effective communication in ensuring compliance with infection control precautions during transitions of care.

A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.

PubMed

Battaglini, Eva; Park, Susanna B; Barnes, Elizabeth H; Goldstein, David

2018-04-20

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. Copyright © 2018 Elsevier Inc. All rights reserved.

A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

PubMed

Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

2013-07-01

Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. Copyright © 2013 Elsevier Inc. All rights reserved.

A feasibility randomised controlled trial of pre-operative occupational therapy to optimise recovery for patients undergoing primary total hip replacement for osteoarthritis (PROOF-THR).

PubMed

Jepson, Paul; Sands, Gina; Beswick, Andrew D; Davis, Edward T; Blom, Ashley W; Sackley, Catherine M

2016-02-01

To assess the feasibility of a pre-operative occupational therapy intervention for patients undergoing primary total hip replacement. Single blinded feasibility randomised controlled trial, with data collection prior to the intervention, and at 4, 12, and 26 weeks following surgery. Recruitment from two NHS orthopaedic outpatient centres in the West Midlands, UK. Patients awaiting primary total hip replacement due to osteoarthritis were recruited. Following pre-operative assessment, patients were individually randomised to intervention or control by a computer-generated block randomisation algorithm stratified by age and centre. The intervention group received a pre-surgery home visit by an occupational therapist who discussed expectations, assessed home safety, and provided appropriate adaptive equipment. The control group received treatment as usual. The study assessed the feasibility of recruitment procedures, delivery of the intervention, appropriateness of outcome measures and data collection methods. Health related quality of life and resource use were recorded at 4, 12 and 26 weeks. Forty-four participants were recruited, 21 were randomised to the occupational therapy intervention and 23 to usual care. Analysis of 26 week data included 18 participants in the intervention group and 21 in the control. The intervention was delivered successfully with no withdrawals or crossovers; 5/44 were lost to follow-up with further missing data for participation and resource use. The feasibility study provided the information required to conduct a definitive trial. Burden of assessment would need to be addressed. A total of 219 patients would be required in an efficacy trial. © The Author(s) 2015.

The potential for improvement of outcomes by personalized insulin treatment of type 1 diabetes as assessed by analysis of single-patient data from a randomized controlled cross-over insulin trial.

PubMed

Pedersen-Bjergaard, Ulrik; Kristensen, Peter L; Beck-Nielsen, Henning; Nørgaard, Kirsten; Perrild, Hans; Christiansen, Jens S; Jensen, Tonny; Parving, Hans-Henrik; Thorsteinsson, Birger; Tarnow, Lise

2017-01-01

The evidence for optimal insulin treatment in type 1 diabetes is mainly based on randomised controlled trials applying a parallel-group design. Such trials yield robust general results but crucial individual treatment effects cannot be extracted. We aimed to assess the potential for further improvement of outcomes by personalized insulin therapy by analyzing data from a cross-over trial at individual level. Post hoc analysis of data from a two-year multicentre, prospective, randomised, open, blinded endpoint (PROBE) trial (the HypoAna trial). In a cross-over design 114 patients with type 1 diabetes and recurrent severe hypoglycemia were treated with basal-bolus therapy based on analog (detemir/aspart) or human (NPH/regular) insulin aiming at maintenance of baseline HbA1c levels. For each patient a superior outcome was defined as fewer events of severe hypoglycemia defined by need for third party treatment assistance or a more than 0.4% (4.4mmol/mol) lower HbA1c. Only one quarter had comparable outcome of the two treatments in terms of rate of severe hypoglycemia or HbA1c. Twice as many patients had superior outcome of analog-based as compared to human insulin-based insulin treatment. The rate of severe hypoglycemia with the superior treatment was lower compared to the rates obtained with analog insulin and with human insulin (0.67, 1.09, and 1.57 episode per patient-year, respectively (p<0.0001)). Personalized insulin treatment of type 1 diabetes based on single-patient evidence may improve outcomes significantly compared to a general treatment approach. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials

PubMed Central

Varadhan, Krishna K; Neal, Keith R

2012-01-01

Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis. PMID:22491789

Use of the learning conversation improves instructor confidence in life support training: An open randomised controlled cross-over trial comparing teaching feedback mechanisms.

PubMed

Baldwin, Lydia J L; Jones, Christopher M; Hulme, Jonathan; Owen, Andrew

2015-11-01

Feedback is vital for the effective delivery of skills-based education. We sought to compare the sandwich technique and learning conversation structured methods of feedback delivery in competency-based basic life support (BLS) training. Open randomised crossover study undertaken between October 2014 and March 2015 at the University of Birmingham, United Kingdom. Six-hundred and forty healthcare students undertaking a European Resuscitation Council (ERC) BLS course were enrolled, each of whom was randomised to receive teaching using either the sandwich technique or the learning conversation. Fifty-eight instructors were randomised to initially teach using either the learning conversation or sandwich technique, prior to crossing-over and teaching with the alternative technique after a pre-defined time period. Outcome measures included skill acquisition as measured by an end-of-course competency assessment, instructors' perception of teaching with each feedback technique and candidates' perception of the feedback they were provided with. Scores assigned to use of the learning conversation by instructors were significantly more favourable than for the sandwich technique across all but two assessed domains relating to instructor perception of the feedback technique, including all skills-based domains. No difference was seen in either assessment pass rates (80.9% sandwich technique vs. 77.2% learning conversation; OR 1.2, 95% CI 0.85-1.84; p=0.29) or any domain relating to candidates' perception of their teaching technique. This is the first direct comparison of two feedback techniques in clinical medical education using both quantitative and qualitative methodology. The learning conversation is preferred by instructors providing competency-based life support training and is perceived to favour skills acquisition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Live lecture versus video podcast in undergraduate medical education: A randomised controlled trial.

PubMed

Schreiber, Benjamin E; Fukuta, Junaid; Gordon, Fabiana

2010-10-08

Information technology is finding an increasing role in the training of medical students. We compared information recall and student experience and preference after live lectures and video podcasts in undergraduate medical education. We performed a crossover randomised controlled trial. 100 students were randomised to live lecture or video podcast for one clinical topic. Live lectures were given by the same instructor as the narrator of the video podcasts. The video podcasts comprised Powerpoint™ slides narrated using the same script as the lecture. They were then switched to the other group for a second clinical topic. Knowledge was assessed using multiple choice questions and qualitative information was collected using a questionnaire. No significant difference was found on multiple choice questioning immediately after the session. The subjects enjoyed the convenience of the video podcast and the ability to stop, review and repeat it, but found it less engaging as a teaching method. They expressed a clear preference for the live lecture format. We suggest that video podcasts are not ready to replace traditional teaching methods, but may have an important role in reinforcing learning and aiding revision.

Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study.

PubMed

Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W; Christensen, Karl; Olesen, Jes

2009-08-01

Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. In this randomised, double-blind, placebo-controlled crossover trial, 40 mg tonabersat once daily was compared with matched placebo in patients who had at least one aura attack per month during the past 3 months. Randomisation was by computer-generated list. Patients kept a detailed diary to enable objective diagnosis of each attack as migraine with aura, migraine without aura, or other type of headache. Primary endpoints were a reduction in aura attacks with or without headache and a reduction in migraine headache days with or without an aura. Analysis was per protocol. This trial is registered, number NCT00332007. 39 patients were included in the study, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly different between placebo and tonabersat groups (3.0 days in each group; p=0.09). Tonabersat was well tolerated but overall had more side-effects than placebo. Tonabersat showed a preventive effect on attacks of migraine aura but no efficacy on non-aura attacks, in keeping with its known inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. Minster Pharmaceuticals; Lundbeck Foundation.

Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

PubMed

Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

2015-03-01

T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

A randomised controlled crossover trial of nurse practitioner versus doctor led outpatient care in a bronchiectasis clinic

PubMed Central

Sharples, L; Edmunds, J; Bilton, D; Hollingworth, W; Caine, N; Keogan, M; Exley, A

2002-01-01

Background: With the decrease in junior doctor hours, the advent of specialist registrars, and the availability of highly trained and experienced nursing personnel, the service needs of patients with chronic respiratory diseases attending routine outpatient clinics may be better provided by appropriately trained nurse practitioners. Methods: A randomised controlled crossover trial was used to compare nurse practitioner led care with doctor led care in a bronchiectasis outpatient clinic. Eighty patients were recruited and randomised to receive 1 year of nurse led care and 1 year of doctor led care in random order. Patients were followed up for 2 years to ensure patient safety and acceptability and to assess differences in lung function. Outcome measures were forced expiratory volume in 1 second (FEV1), 12 minute walk test, health related quality of life, and resource use. Results: The mean difference in FEV1 was 0.2% predicted (95% confidence interval –1.6 to 2.0%, p=0.83). There were no significant differences in the other clinical or health related quality of life measures. Nurse led care resulted in significantly increased resource use compared with doctor led care (mean difference £1497, 95% confidence interval £688 to £2674, p<0.001), a large part of which resulted from the number and duration of hospital admissions. The mean difference in resource use was greater in the first year (£2625) than in the second year (£411). Conclusions: Nurse practitioner led care for stable patients within a chronic chest clinic is safe and is as effective as doctor led care, but may use more resources. PMID:12149523

Evaluation of eLearning for the teaching of undergraduate ophthalmology at medical school: a randomised controlled crossover study.

PubMed

Petrarca, Caroline A; Warner, Julia; Simpson, Andrew; Petrarca, Robert; Douiri, Abdel; Byrne, David; Jackson, Timothy L

2018-05-25

To compare ophthalmology teaching delivered by eLearning with traditional lectures, in terms of undergraduate performance and satisfaction. Randomised controlled crossover study at King's College London Medical School with 245 third year medical students. The ophthalmology syllabus was divided into ten topics. Five topics were randomised to be taught by traditional lectures and five by electronic learning (eLearning). For the second rotation of students the topics were crossed over, so that those topics taught by traditional lectures were taught by eLearning and vice versa. At the end of each rotation the students sat an optional online mock examination containing 100 questions (ten on each topic). Students' examination performance was compared between the two teaching methods. Student satisfaction was assessed using an online satisfaction survey. Outcome measures were the mean percentage of correct answers across all ten topics, student satisfaction and self-assessed knowledge. The mean examination score for questions taught by eLearning was 58% (95% CI, 55.7-59.6), versus 55% (95% CI 53.1-56.8) for traditional lectures (P = 0.047). Across all topics students were more satisfied with eLearning than traditional lectures, with 87% (95% CI 84.5-88.4) rating eLearning as 'excellent' or 'good' versus 65% (95% CI 62.0-67.4) for lectures (p < 0.0001). Overall 180 (75.6%) preferred eLearning compared to traditional lectures, with 166 (69.7%) rating eLearning 'much better' or 'better,' 61 (25.6%) 'neutral' and 11 (4.6%) 'worse' or 'much worse.' Student satisfaction and examination performance are both enhanced by ophthalmology eLearning. Similar eLearning modules may be suitable for other specialties and postgraduate learning.

The impact of insecticide-treated school uniforms on dengue infections in school-aged children: study protocol for a randomised controlled trial in Thailand

PubMed Central

2012-01-01

Background There is an urgent need to protect children against dengue since this age group is particularly sensitive to the disease. Since dengue vectors are active mainly during the day, a potential target for control should be schools where children spend a considerable amount of their day. School uniforms are the cultural norm in most developing countries, worn throughout the day. We hypothesise that insecticide-treated school uniforms will reduce the incidence of dengue infection in school-aged children. Our objective is to determine the impact of impregnated school uniforms on dengue incidence. Methods A randomised controlled trial will be conducted in eastern Thailand in a group of schools with approximately 2,000 students aged 7–18 years. Pre-fabricated school uniforms will be commercially treated to ensure consistent, high-quality insecticide impregnation with permethrin. A double-blind, randomised, crossover trial at the school level will cover two dengue transmission seasons. Discussion Practical issues and plans concerning intervention implementation, evaluation, analysing and interpreting the data, and possible policy implications arising from the trial are discussed. Trial registration clinicaltrial.gov. Registration number: NCT01563640 PMID:23153360

An Intervention with Mineral Water Decreases Cardiometabolic Risk Biomarkers. A Crossover, Randomised, Controlled Trial with Two Mineral Waters in Moderately Hypercholesterolaemic Adults.

PubMed

Toxqui, Laura; Vaquero, M Pilar

2016-06-28

Water intake is essential for health maintenance and disease prevention. The effects of an intervention with two mineral waters, sodium-bicarbonated mineral water (BW) or control mineral water low in mineral content (CW), on cardiometabolic risk biomarkers were studied. In a randomised-controlled crossover-trial, sixty-four moderately hypercholesterolaemic adults were randomly assigned to consume 1 L/day of either BW (sodium, 1 g/L; bicarbonate, 2 g/L) or CW with the main meals for eight weeks, separated by an eight-week washout period. Blood lipids, lipid oxidation, glucose, insulin, aldosterone, urine pH, urinary electrolytes, blood pressure, body weight, fluid intake, energy, and nutrients from total diet and beverages were determined. Total cholesterol, LDL cholesterol, and glucose decreased (p < 0.01), oxidised LDL tended to decrease (p = 0.073), and apolipoprotein B increased during the intervention, without water type effect. Energy and carbohydrates from beverages decreased since soft drinks and fruit juice consumptions decreased throughout the trial. BW increased urinary pH (p = 0.006) and reduced calcium/creatinine excretion (p = 0.011). Urinary potassium/creatinine decreased with both waters. Consumption of 1 L/day of mineral water with the main meals reduces cardiometabolic risk biomarkers, likely to be attributed to a replacement of soft drinks by water. In addition, BW does not affect blood pressure and exerts a moderate alkalizing effect in the body.

Effects of hypoglycaemia on working memory and regional cerebral blood flow in type 1 diabetes: a randomised, crossover trial.

PubMed

Gejl, Michael; Gjedde, Albert; Brock, Birgitte; Møller, Arne; van Duinkerken, Eelco; Haahr, Hanne L; Hansen, Charlotte T; Chu, Pei-Ling; Stender-Petersen, Kirstine L; Rungby, Jørgen

2018-03-01

The aim of this randomised, crossover trial was to compare cognitive functioning and associated brain activation patterns during hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in individuals with type 1 diabetes mellitus. In this patient-blinded, crossover study, 26 participants with type 1 diabetes mellitus attended two randomised experimental visits: one hypoglycaemic clamp (PG 2.8 ± 0.2 mmol/l, approximate duration 55 min) and one euglycaemic clamp (PG 5.5 mmol/l ± 10%). PG levels were maintained by hyperinsulinaemic glucose clamping. Cognitive functioning was assessed during hypoglycaemia and euglycaemia conditions using a modified version of the digit symbol substitution test (mDSST) and control DSST (cDSST). Simultaneously, regional cerebral blood flow (rCBF) was measured in pre-specified brain regions by six H 2 15 O-positron emission tomographies (PET) per session. Working memory was impaired during hypoglycaemia as indicated by a statistically significantly lower mDSST score (estimated treatment difference [ETD] -0.63 [95% CI -1.13, -0.14], p = 0.014) and a statistically significantly longer response time (ETD 2.86 s [7%] [95% CI 0.67, 5.05], p = 0.013) compared with euglycaemia. During hypoglycaemia, mDSST task performance was associated with increased activity in the frontal lobe regions, superior parietal lobe and thalamus, and decreased activity in the temporal lobe regions (p < 0.05). Working memory activation (mDSST - cDSST) statistically significantly increased blood flow in the striatum during hypoglycaemia (ETD 0.0374% [95% CI 0.0157, 0.0590], p = 0.002). During hypoglycaemia (mean PG 2.9 mmol/l), working memory performance was impaired. Altered performance was associated with significantly increased blood flow in the striatum, a part of the basal ganglia implicated in regulating motor functions, memory, language and emotion. NCT01789593, clinicaltrials.gov FUNDING: This study was funded by Novo Nordisk.

A randomised study of leadership interventions for healthcare managers.

PubMed

Lornudd, Caroline; Bergman, David; Sandahl, Christer; von Thiele Schwarz, Ulrica

2016-10-03

Purpose The purpose of this paper was to assess two different leader development interventions by comparing their effects on leadership behaviour and evaluating their combined impact after two years, from the viewpoints of both the participating managers and external raters. Design/methodology/approach The study was a longitudinal randomised controlled trial with a cross-over design. Health care managers ( n = 177) were first randomised to either of two 10-month interventions and a year later were switched to the other intervention. Leadership behaviour was rated at pre-test and 12 and 24 months by participating managers and their superiors, colleagues and subordinates using a 360-degree instrument. Analysis of variance and multilevel regression analysis was performed. Findings No difference in effect on leadership behaviour was found between the two interventions. The evaluation of the combined effect of the interventions on leadership behaviour showed inconsistent (i.e. both increased and decreased) ratings by the various rater sources. Practical implications This study provides some evidence that participation in leadership development programmes can improve managers' leadership behaviours, but the results also highlight the interpretive challenges connected with using a 360-degree instrument to evaluate such development. Originality/value The longitudinal randomised controlled design and the large sample comprising both managers and external raters make this study unusually rigorous in the field of leadership development evaluations.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

PubMed

Lockyer, Stacey; Corona, Giulia; Yaqoob, Parveen; Spencer, Jeremy P E; Rowland, Ian

2015-07-14

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

Effect of sleep deprivation after a night shift duty on simulated crisis management by residents in anaesthesia. A randomised crossover study.

PubMed

Arzalier-Daret, Ségolène; Buléon, Clément; Bocca, Marie-Laure; Denise, Pierre; Gérard, Jean-Louis; Hanouz, Jean-Luc

2018-04-01

Sleep deprivation has been associated with an increased incidence of medical errors and can jeopardise patients' safety during medical crisis management. The aim of the study was to assess the effect of sleep deprivation on the management of simulated anaesthesia crisis by residents in anaesthesiology. A randomised, comparative, monocentric crossover study involving 48 residents in anaesthesia was performed on a high fidelity patient simulator. Each resident was evaluated in a sleep-deprived state (deprived group, after a night shift duty) and control state (control group, after a night of sleep). Performance was assessed through points obtained during crisis scenario 1 (oesophageal intubation followed by anaphylactic shock) and scenario 2 (anaesthesia-related bronchospasm followed by ventricular tachycardia). Sleep periods were recorded by actigraphy. Two independent observers assessed the performances. The primary endpoint of the study was the score obtained for each scenario. Resident's crisis management performance is associated with sleep deprivation (scenario 1: control=39 [33-42] points vs. deprived=26 [19-40] points, P=0.02; scenario 2: control=21 [17-24] vs. deprived=14 [12-19], P=0.01). The main errors observed were: error in drug administration and dose, delay in identification of hypotension, and missing communication with the surgical team about situation. The present study showed that sleep deprivation is associated with impairment of performance to manage crisis situations by residents in anaesthesia. Copyright © 2017 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

The use of portable video media vs standard verbal communication in the urological consent process: a multicentre, randomised controlled, crossover trial.

PubMed

Winter, Matthew; Kam, Jonathan; Nalavenkata, Sunny; Hardy, Ellen; Handmer, Marcus; Ainsworth, Hannah; Lee, Wai Gin; Louie-Johnsun, Mark

2016-11-01

To determine if portable video media (PVM) improves patient's knowledge and satisfaction acquired during the consent process for cystoscopy and insertion of a ureteric stent compared to standard verbal communication (SVC), as informed consent is a crucial component of patient care and PVM is an emerging technology that may help improve the consent process. In this multi-centre randomised controlled crossover trial, patients requiring cystoscopy and stent insertion were recruited from two major teaching hospitals in Australia over a 15-month period (July 2014-December 2015). Patient information delivery was via PVM and SVC. The PVM consisted of an audio-visual presentation with cartoon animation presented on an iPad. Patient satisfaction was assessed using the validated Client Satisfaction Questionnaire 8 (CSQ-8; maximum score 32) and knowledge was tested using a true/false questionnaire (maximum score 28). Questionnaires were completed after first intervention and after crossover. Scores were analysed using the independent samples t-test and Wilcoxon signed-rank test for the crossover analysis. In all, 88 patients were recruited. A significant 3.1 point (15.5%) increase in understanding was demonstrable favouring the use of PVM (P < 0.001). There was no difference in patient satisfaction between the groups as judged by the CSQ-8. A significant 3.6 point (17.8%) increase in knowledge score was seen when the SVC group were crossed over to the PVM arm. A total of 80.7% of patients preferred PVM and 19.3% preferred SVC. Limitations include the lack of a validated questionnaire to test knowledge acquired from the interventions. This study demonstrates patients' preference towards PVM in the urological consent process of cystoscopy and ureteric stent insertion. PVM improves patient's understanding compared with SVC and is a more effective means of content delivery to patients in terms of overall preference and knowledge gained during the consent process. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

The effect of a cinnamon-, chromium- and magnesium-formulated honey on glycaemic control, weight loss and lipid parameters in type 2 diabetes: an open-label cross-over randomised controlled trial.

PubMed

Whitfield, Patricia; Parry-Strong, Amber; Walsh, Emily; Weatherall, Mark; Krebs, Jeremy D

2016-04-01

This randomised controlled trial assessed the acute and long-term effects of daily supplementation of kanuka honey, formulated with cinnamon, chromium and magnesium on glucose metabolism, weight and lipid parameters in individuals with type 2 diabetes. Twelve individuals with type 2 diabetes received 53.5 g of a formulated honey and a control (non-formulated) kanuka honey in a random order for 40 days, using cross-over design. Fasting glucose, insulin, HbA1c, lipids and anthropometric measures were measured at baseline and end of treatment. A meal tolerance test was performed at baseline to assess acute metabolic response. There was no statistically significant difference in acute glucose metabolism between treatment groups, as measured by the Matsuda index and AUC for glucose and insulin. After the 40-day intervention with honey, fasting glucose did not differ significantly between the two treatments (95 % CI -2.6 to 0.07). There was no statistically significant change in HbA1c or fasting insulin. There was a statistically significant reduction in total cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23), LDL cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23) and weight by -2.2 kg (95 % CI -4.2 to -0.1). There was a trend towards increased HDL and reduced systolic blood pressure in the intervention treatment. The addition of cinnamon, chromium and magnesium supplementation to kanuka honey was not associated with a significant improvement in glucose metabolism or glycaemic control in individuals with type 2 diabetes. Use of the formulated honey was associated with a reduction in weight and improvements in lipid parameters, and should be investigated further.

Live lecture versus video podcast in undergraduate medical education: A randomised controlled trial

PubMed Central

2010-01-01

Background Information technology is finding an increasing role in the training of medical students. We compared information recall and student experience and preference after live lectures and video podcasts in undergraduate medical education. Methods We performed a crossover randomised controlled trial. 100 students were randomised to live lecture or video podcast for one clinical topic. Live lectures were given by the same instructor as the narrator of the video podcasts. The video podcasts comprised Powerpoint™ slides narrated using the same script as the lecture. They were then switched to the other group for a second clinical topic. Knowledge was assessed using multiple choice questions and qualitative information was collected using a questionnaire. Results No significant difference was found on multiple choice questioning immediately after the session. The subjects enjoyed the convenience of the video podcast and the ability to stop, review and repeat it, but found it less engaging as a teaching method. They expressed a clear preference for the live lecture format. Conclusions We suggest that video podcasts are not ready to replace traditional teaching methods, but may have an important role in reinforcing learning and aiding revision. PMID:20932302

Naturalistic conversation improves daytime motorway driving performance under a benzodiazepine: a randomised, crossover, double-blind, placebo-controlled study.

PubMed

Moták, Ladislav; Bayssac, Laëtitia; Taillard, Jacques; Sagaspe, Patricia; Huet, Nathalie; Terrier, Patrice; Philip, Pierre; Daurat, Agnès

2014-06-01

The adverse effects of benzodiazepines on driving are widely recognised. The aims of this study were both to determine the impact of naturalistic conversation on the driving ability of drivers under a benzodiazepine, and to measure the accuracy of drivers' assessments of the joint effects of the benzodiazepine and conversation. Sixteen healthy male participants (29.69 ± 3.30 years) underwent a randomised, crossover, double-blind, placebo-controlled study with the benzodiazepine lorazepam (2mg). They drove 200 km (125 miles) on a motorway in the morning. We measured two driving ability-related variables (i.e., lane-keeping performance), and collected a set of self-assessed variables (i.e., self-assessment of driving performance) during two 10-min sequences of interest (no conversation vs. conversation). An analysis of variance revealed an interaction whereby lane-keeping performance under lorazepam was worse in the no-conversation condition than in the conversation condition. No such difference was detected under placebo. Pearson's correlation coefficients revealed that self-assessments were (i) not at all predictive of lane-keeping when performed before the drive, but (ii) moderately predictive of lane-keeping performance when performed during or after the drive. We conclude that conversation with a passenger may contribute to safer lane-keeping when driving under a benzodiazepine. Moreover, a degree of awareness may be attained after some experience of driving under the influence of this type of medication. Copyright © 2014 Elsevier Ltd. All rights reserved.

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design.

PubMed

Malde, Marian K; Bügel, Susanne; Kristensen, Mette; Malde, Ketil; Graff, Ingvild E; Pedersen, Jan I

2010-07-20

Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Mean Ca absorption (+/- SEE) from the three different Ca sources were 21.9 +/- 1.7%, 22.5 +/- 1.7% and 27.4 +/- 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements.

Calcium from salmon and cod bone is well absorbed in young healthy men: a double-blinded randomised crossover design

PubMed Central

2010-01-01

Background Calcium (Ca) - fortified foods are likely to play an important role in helping the consumer achieve an adequate Ca intake, especially for persons with a low intake of dairy products. Fish bones have a high Ca content, and huge quantities of this raw material are available as a by-product from the fish industry. Previously, emphasis has been on producing high quality products from fish by-products by use of bacterial proteases. However, documentation of the nutritional value of the enzymatically rinsed Ca-rich bone fraction remains unexplored. The objective of the present study was to assess the bioavailability of calcium in bones of Atlantic salmon (oily fish) and Atlantic cod (lean fish) in a double-blinded randomised crossover design. Methods Ca absorption was measured in 10 healthy young men using 47Ca whole body counting after ingestion of a test meal extrinsically labelled with the 47Ca isotope. The three test meals contained 800 mg of Ca from three different calcium sources: cod bones, salmon bones and control (CaCO3). Results Mean Ca absorption (± SEE) from the three different Ca sources were 21.9 ± 1.7%, 22.5 ± 1.7% and 27.4 ± 1.8% for cod bones, salmon bones, and control (CaCO3), respectively. Conclusion We conclude that bones from Atlantic salmon and Atlantic cod are suitable as natural Ca sources in e.g. functional foods or as supplements. PMID:20646299

The Tulip GT® airway versus the facemask and Guedel airway: a randomised, controlled, cross-over study by Basic Life Support-trained airway providers in anaesthetised patients.

PubMed

Shaikh, A; Robinson, P N; Hasan, M

2016-03-01

We performed a randomised, controlled, cross-over study of lung ventilation by Basic Life Support-trained providers using either the Tulip GT® airway or a facemask with a Guedel airway in 60 anaesthetised patients. Successful ventilation was achieved if the provider produced an end-tidal CO2 > 3.5 kPa and a tidal volume > 250 ml in two of the first three breaths, within 60 sec and within two attempts. Fifty-seven (95%) providers achieved successful ventilation using the Tulip GT compared with 35 (58%) using the facemask (p < 0.0001). Comparing the Tulip GT and facemask, the mean (SD) end-tidal CO2 was 5.0 (0.7) kPa vs 2.5 (1.5) kPa, tidal volume was 494 (175) ml vs 286 (186) ml and peak inspiratory pressure was 18.3 (3.4) cmH2 O vs 13.6 (7) cmH2 O respectively (all p < 0.0001). Forty-seven (78%) users favoured the Tulip GT airway. These results are similar to a previous manikin study using the same protocol, suggesting a close correlation between human and manikin studies for this airway device. We conclude that the Tulip GT should be considered as an adjunct to airway management both within and outside hospitals when ventilation is being undertaken by Basic Life Support-trained airway providers. © 2015 The Association of Anaesthetists of Great Britain and Ireland.

Heat strain evaluation of overt and covert body armour in a hot and humid environment.

PubMed

Pyke, Andrew J; Costello, Joseph T; Stewart, Ian B

2015-03-01

The aim of this study was to elucidate the thermophysiological effects of wearing lightweight non-military overt and covert personal body armour (PBA) in a hot and humid environment. Eight healthy males walked on a treadmill for 120 min at 22% of their heart rate reserve in a climate chamber simulating 31 °C (60%RH) wearing either no armour (control), overt or covert PBA in addition to a security guard uniform, in a randomised controlled crossover design. No significant difference between conditions at the end of each trial was observed in core temperature, heart rate or skin temperature (P > 0.05). Covert PBA produced a significantly greater amount of body mass change (-1.81 ± 0.44%) compared to control (-1.07 ± 0.38%, P = 0.009) and overt conditions (-1.27 ± 0.44%, P = 0.025). Although a greater change in body mass was observed after the covert PBA trial; based on the physiological outcome measures recorded, the heat strain encountered while wearing lightweight, non-military overt or covert PBA was negligible compared to no PBA. The wearing of bullet proof vests or body armour is a requirement of personnel engaged in a wide range of occupations including police, security, customs and even journalists in theatres of war. This randomised controlled crossover study is the first to examine the thermophysiological effects of wearing lightweight non-military overt and covert personal body armour (PBA) in a hot and humid environment. We conclude that the heat strain encountered while wearing both overt and covert lightweight, non-military PBA was negligible compared to no PBA. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults.

PubMed

Lamport, Daniel J; Pal, Deepa; Macready, Anna L; Barbosa-Boucas, Sofia; Fletcher, John M; Williams, Claire M; Spencer, Jeremy P E; Butler, Laurie T

2016-12-01

A plausible mechanism underlying flavonoid-associated cognitive effects is increased cerebral blood flow (CBF). However, behavioural and CBF effects following flavanone-rich juice consumption have not been explored. The aim of this study was to investigate whether consumption of flavanone-rich juice is associated with acute cognitive benefits and increased regional CBF in healthy, young adults. An acute, single-blind, randomised, cross-over design was applied with two 500-ml drink conditions - high-flavanone (HF; 70·5 mg) drink and an energy-, and vitamin C- matched, zero-flavanone control. A total of twenty-four healthy young adults aged 18-30 years underwent cognitive testing at baseline and 2-h after drink consumption. A further sixteen, healthy, young adults were recruited for functional MRI assessment, whereby CBF was measured with arterial spin labelling during conscious resting state at baseline as well as 2 and 5 h after drink consumption. The HF drink was associated with significantly increased regional perfusion in the inferior and middle right frontal gyrus at 2 h relative to baseline and the control drink. In addition, the HF drink was associated with significantly improved performance on the Digit Symbol Substitution Test at 2 h relative to baseline and the control drink, but no effects were observed on any other behavioural cognitive tests. These results demonstrate that consumption of flavanone-rich citrus juice in quantities commonly consumed can acutely enhance blood flow to the brain in healthy, young adults. However, further studies are required to establish a direct causal link between increased CBF and enhanced behavioural outcomes following citrus juice ingestion.

Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study.

PubMed

Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

2017-09-01

Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Impact of cooked functional meat enriched with omega-3 fatty acids and rosemary extract on inflammatory and oxidative status; a randomised, double-blind, crossover study.

PubMed

Bermejo, L M; López-Plaza, B; Weber, T K; Palma-Milla, S; Iglesias, C; Reglero, G; Gómez-Candela, C

2014-11-01

n-3 fatty acid intake has been associated with inflammatory benefits in cardiovascular disease (CVD). Functionalising meat may be of great interest. The aim of the present study was to assess the effect of functional meat containing n-3 and rosemary extract on inflammatory and oxidative status markers in subjects with risk for CVD. A randomised, double-blind, cross-over study was undertaken to compare the effects on the above markers of consuming functional or control meat products. 43 volunteers with at least two lipid profile variables showing risk for CVD were randomly assigned to receive functional meat (FM) or control meat (CM) over 12-weeks with a 4-week wash-out interval before crossover. Functional effects were assessed by examining lipid profile, CRP, PAI-1, TNF-alpha, IL-6, fibrinogen (inflammatory markers), and TBARS, FRAP and 8-iso-PGF2 (oxidative status markers). 33 subjects (24 women) aged 50.7±8.8 years completed the study. In FM treatment, PAI-1, fibrinogen and 8-iso-PGF2 decreased significantly after 12 weeks, while FRAP significantly increased. In contrast, in CM treatment, a significant increase was seen in PAI-1, while FRAP significantly declined. Significant differences were also seen between the FM and CM treatments after 12 weeks in terms of the change observed in PAI-1, FRAP and 8-iso-PGF2 values. No significant differences were seen in anthropometric variables nor were adverse effects reported. The consumption of FM containing n-3 and rosemary extract improved oxidative and inflammatory status of people with at least two lipid profile variables showing risk for CVD. The inclusion of such functional meat in a balanced diet might be a healthy lifestyle option. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

EFFECT of daily antiseptic body wash with octenidine on nosocomial primary bacteraemia and nosocomial multidrug-resistant organisms in intensive care units: design of a multicentre, cluster-randomised, double-blind, cross-over study

PubMed Central

Meißner, Anne; Hasenclever, Dirk; Brosteanu, Oana; Chaberny, Iris Freya

2017-01-01

Introduction Nosocomial infections are serious complications that increase morbidity, mortality and costs and could potentially be avoidable. Antiseptic body wash is an approach to reduce dermal micro-organisms as potential pathogens on the skin. Large-scale trials with chlorhexidine as the antiseptic agent suggest a reduction of nosocomial infection rates. Octenidine is a promising alternative agent which could be more effective against Gram-negative organisms. We hypothesise that daily antiseptic body wash with octenidine reduces the risk of intensive care unit (ICU)-acquired primary bacteraemia and ICU-acquired multidrug-resistant organisms (MDRO) in a standard care setting. Methods and analysis EFFECT is a controlled, cluster-randomised, double-blind study. The experimental intervention consists in using octenidine-impregnated wash mitts for the daily routine washing procedure of the patients. This will be compared with using placebo wash mitts. Replacing existing washing methods is the only interference into clinical routine. Participating ICUs are randomised in an AB/BA cross-over design. There are two 15-month periods, each consisting of a 3-month wash-out period followed by a 12-month intervention and observation period. Randomisation determines only the sequence in which octenidine-impregnated or placebo wash mitts are used. ICUs are left unaware of what mitts packages they are using. The two coprimary endpoints are ICU-acquired primary bacteraemia and ICU-acquired MDRO. Endpoints are defined based on individual ward-movement history and microbiological test results taken from the hospital information systems without need for extra documentation. Data on clinical symptoms of infection are not collected. EFFECT aims at recruiting about 45 ICUs with about 225 000 patient-days per year. Ethics and dissemination The study was approved by the ethics committee of the University of Leipzig (number 340/16-ek) in November 2016. Findings will be published in peer-reviewed journals. Trial registration number DRKS-ID: DRKS00011282. PMID:29122787

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

PubMed Central

Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

2016-01-01

Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

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

PubMed

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

2017-01-01

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

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

PubMed

Costello, Joseph T; Baker, Philip R A; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

2015-09-18

Recovery strategies are often used with the intention of preventing or minimising muscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts.The searches were run in August 2015. We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity. We assessed the quality of the evidence using GRADE. Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as 'very low' quality based on the GRADE criteria.Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC.All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95% CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events.One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reported muscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

Oral health-related quality of life in patients with non-metal clasp dentures: a randomised cross-over trial.

PubMed

Fueki, K; Yoshida-Kohno, E; Wakabayashi, N

2017-05-01

We investigated the efficacy of non-metal clasp dentures (NMCDs) with regard to the oral health-related quality of life (OHRQoL) and compare the findings with those for conventional metal clasp-retained dentures (MCDs). This single-centre, randomised controlled, two-phase, open label, cross-over trial included 28 partially dentate individuals. The patients were randomised to receive MCDs followed by NMCDs, or the opposite sequence (n = 14 in each group); each denture was worn for 3 months. OHRQoL was evaluated using the Oral Health Impact Profile-Japanese version (OHIP-J) at entry (T-entry; before treatment with the first denture) and at 3 months after treatment with each denture (T3). An examiner evaluated denture stability, oral appearance and surface roughness before denture delivery (T0) and at T3 and denture hygiene at T3. A total of 24 patients completed the trial. There were no complications related to the dentures, abutment teeth or denture-bearing mucosa during the follow-up periods for both dentures. The mean OHIP summary score was lower for NMCDs than for MCDs, and the difference (9 points) was greater than the minimal important difference (6 points), indicating the difference was clinically relevant. The effect size was medium (0·70). Statistical analyses with linear mixed models found a significant effect of the denture type on the OHIP summary score and scores for the Oro-facial appearance, Oro-facial pain and Psychological impact domains (NMCD < MCD; P < 0·05). The results of our study suggest that NMCDs allow for better OHRQoL compared with MCDs. © 2017 John Wiley & Sons Ltd.

Effects of lipid emulsion particle size on satiety and energy intake: a randomised cross-over trial.

PubMed

Poppitt, Sally D; Budgett, Stephanie C; MacGibbon, Alastair K; Quek, Siew-Young; Kindleysides, Sophie; Wiessing, Katy R

2018-03-01

Emulsified lipids, with central lipid core surrounded by polar lipid 'protective coat', have been proposed to stimulate the ileal brake, alter appetite, food intake and aid weight control. In addition to lipid composition, emulsion particle size may contribute to efficacy with small droplets providing a larger surface area for gastrointestinal (GI) lipase action and larger droplets prolonging and delaying digestion in the GI tract. Tube feeding studies delivering emulsions directly into the small intestine show clear effects of smaller particle size on appetite and food intake, but evidence from oral feeding studies is sparse. The objective of this study was to determine the effects of lipid emulsion particle size on appetite response and food intake. In a three-arm randomised cross-over, high-phospholipid (PL) dairy lipid emulsions or matched control were consumed at breakfast within a yoghurt smoothie: (i) large-particle size emulsion, LPE (diameter 0.759 µm, 10 g lipid emulsion, 190 g yoghurt), (ii) small-particle size emulsion, SPE (diameter 0.290 µm, 10 g lipid emulsion, 190 g yoghurt), (iii) control non-emulsion, NE (10 g non-emulsion lipid, 190 g yoghurt). Twenty male participants completed the study, where postprandial appetite response was rated using visual analogue scales (VAS) and ad libitum energy intake at a lunch meal measured 3 h later. There was a trend for LPE to suppress hunger (P = 0.08) and enhance fullness (P = 0.24) relative to both SPE and NE but not statistically significant, and no significant effect of either emulsion on food intake at the lunch meal (P > 0.05). Altering particle size of a high-PL emulsion did not enhance satiety or alter eating behaviour in a group of lean men.

A randomised, double-blind, cross-over trial to evaluate bread, in which gluten has been pre-digested by prolyl endoprotease treatment, in subjects self-reporting benefits of adopting a gluten-free or low-gluten diet.

PubMed

Rees, Dinka; Holtrop, Grietje; Chope, Gemma; Moar, Kim M; Cruickshank, Morven; Hoggard, Nigel

2018-03-01

The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour. Compared with controls, GS subjects had a favourable cardiovascular lipid profile - lower LDL (4·0 (sem 0·3) v. 2·8 (sem 0·2) mmol/l; P=0·008) and LDL:HDL ratio (3·2 (sem 0·4) v. 1·8 (sem 0·2); P=0·005) and modified haematological profile. The majority of the GS subjects followed a low-gluten lifestyle, which helps to reduce the gastrointestinal (GI) symptoms severity. The low-gluten lifestyle does not have any effect on the quality of life, fatigue or mental state of this population. Consumption of normal wheat bread increased GI symptoms in GS subjects compared with their habitual diet. ANPEP lowered the immunogenic gluten in the treated bread by approximately 40 %. However, when compared with the control bread for inducing GI symptoms, no treatment effects were apparent. ANPEP can be applied in the production of bread with taste, texture and appearance comparable with standard bread.

Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.

PubMed

Weis, S; Hagel, S; Schmitz, R P H; Scherag, A; Brunkhorst, F M; Forstner, C; Löffler, B; Pletz, M W

2017-04-08

Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question. SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC. We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media. DRKS00010135. 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/.

Push versus gravity for intermittent bolus gavage tube feeding of premature and low birth weight infants.

PubMed

Dawson, Jennifer A; Summan, Ravinder; Badawi, Nadia; Foster, Jann P

2012-11-14

Many small, sick and premature infants are unable to coordinate sucking, swallowing and breathing, and therefore, require gavage feeding. In gavage feeding, milk feeds are delivered through a tube passed via the nose or mouth into the stomach. Intermittent bolus milk feeds may be administered using a syringe to gently push milk into the infant's stomach (push feed). Alternatively, milk can be poured into a syringe attached to the tube and allowed to drip in by gravity (gravity feed). To determine whether the use of push compared with gravity gavage feeding results in a more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight, infants who require intermittent bolus gavage feeding. We searched the following electronic databases to locate randomised controlled or quasi-randomised trials: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 5), MEDLINE (from 1966 to May 2012), EMBASE (from 1980 to May 2012), and CINAHL (from 1982 to May 2012). We used the standard search strategy of the Cochrane Neonatal Review Group. Randomised or quasi-randomised controlled trials comparing push versus gravity intermittent gavage tube feeding in premature or low birth weight, or both, infants. We assessed the methodology of trials regarding blinding of randomisation and outcome measurement. We evaluated treatment effect with a fixed-effect model using risk ratio (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data; and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We analysed outcomes measured as count data, for example frequency of apnoea, bradycardia and episodes of pulse oximeter oxygen (SpO(2)) desaturation, by comparing rates of events and the rate ratio. We evaluated heterogeneity to help determine the suitability of pooling results. Only one small cross-over trial met the criteria for inclusion in this review and therefore meta-analysis for any of the treatment outcomes was not performed. Symon 1994 reported a trend towards a higher respiratory rate at 10 to 30 minutes following push gavage feeding and no statistical difference in the time taken to give the feeds regardless of the method used. There was one small cross-over study that was included in this review. There is insufficient evidence to recommend either method of gavage feeding. A randomised trial is needed to evaluate the benefits and harms of push versus gravity bolus tube feeding in preterm infants. Infants should be stratified by gestational age at birth (above and below 32 weeks) or birth weight (above and below 1500 grams) and respiratory support (ventilated versus non-ventilated) and the sample size should be of sufficient size to evaluate the primary outcomes outlined in this review (time to establish full tube feeds and feeding intolerance).

A randomised control crossover trial of a theory based intervention to improve sun-safe and healthy behaviours in construction workers: study protocol.

PubMed

Nioi, Amanda; Wendelboe-Nelson, Charlotte; Cowan, Sue; Cowie, Hilary; Rashid, Shahzad; Ritchie, Peter; Cherrie, Mark; Lansdown, Terry C; Cherrie, John W

2018-02-15

Exposure to sunlight can have both positive and negative health impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause skin cancer, however insufficient exposure to sunlight has a detrimental effect on production of Vitamin D. In the construction industry there are onsite proactive behaviours for safety, but sun-safety remains a low priority. There is limited research on understanding the barriers to adopting sun-safe behaviours and the association this may have with Vitamin D production. This paper reports a protocol for an intervention study, using text messaging in combination with a supportive smartphone App. The intervention aims to both reduce UV exposure during months with higher UV levels and promote appropriate dietary changes to boost Vitamin D levels during months with low UV levels. Approximately 60 construction workers will be recruited across the United Kingdom. A randomised control crossover trial (RCCT) will be used to test the intervention, with randomisation at site level - i.e. participants will receive both the control (no text messages or supportive App support) and intervention (daily text messages and supportive App). Using the Theory of Planned Behaviour (TPB) the intervention focuses on supporting sun-safety and healthy dietary decisions in relation to Vitamin D intake. The intervention emphasises cultivating the perception of normative support in the workplace, increasing awareness of control and self-efficacy in taking sun-protective behaviours, making healthier eating choices to boost Vitamin D, and tackling stigmas attached to image and group norms. Each study epoch will last 21 days with intervention text messages delivered on workdays only. The supportive App will provide supplementary information about sun protective behaviours and healthy dietary choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level (obtained using blood spot sampling), which will be taken pre and post control and intervention periods. Secondary outcome measures are two-fold, (1) using the TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK peak radiation season (April-September) using body-mounted UV sensors. This study will provide important information about the effectiveness of a technology-based intervention to promote sun-safety and healthy behaviours in outdoor construction workers. ISRCTN15888934 retrospectively registered 15.01.2018.

Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.

PubMed

Kirschner, J; Schorling, D; Hauschke, D; Rensing-Zimmermann, C; Wein, U; Grieben, U; Schottmann, G; Schara, U; Konrad, K; Müller-Felber, W; Thiele, S; Wilichowski, E; Hobbiebrunken, E; Stettner, G M; Korinthenberg, R

2014-02-01

In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III. Copyright © 2013 Elsevier B.V. All rights reserved.

Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis

PubMed Central

Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

2015-01-01

Background Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. Aim To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Methods Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Results Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. Conclusions This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. PMID:25339518

Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study

PubMed Central

Ossoukhova, Anastasia; Owen, Lauren; Ibarra, Alvin; Pipingas, Andrew; He, Kan; Roller, Marc; Stough, Con

2010-01-01

Rationale Over the last decade, Asian ginseng (Panax ginseng) has been shown to improve aspects of human cognitive function. American ginseng (Panax quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising cognitive enhancing properties in preclinical studies and benefits processes linked to human cognition. Objectives The availability of a highly standardised extract of P. quinquefolius (Cereboost™) led us to evaluate its neurocognitive properties in humans for the first time. Methods This randomised, double-blind, placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg) of Cereboost™ (P. quinquefolius standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6 h following administration. Results There was a significant improvement of working memory (WM) performance associated with P. quinquefolius. Corsi block performance was improved by all doses at all testing times. There were differential effects of all doses on other WM tasks which were maintained across the testing day. Choice reaction time accuracy and ‘calmness’ were significantly improved by 100 mg. There were no changes in blood glucose levels. Conclusions This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile. PMID:20676609

The quality of reporting in cluster randomised crossover trials: proposal for reporting items and an assessment of reporting quality.

PubMed

Arnup, Sarah J; Forbes, Andrew B; Kahan, Brennan C; Morgan, Katy E; McKenzie, Joanne E

2016-12-06

The cluster randomised crossover (CRXO) design is gaining popularity in trial settings where individual randomisation or parallel group cluster randomisation is not feasible or practical. Our aim is to stimulate discussion on the content of a reporting guideline for CRXO trials and to assess the reporting quality of published CRXO trials. We undertook a systematic review of CRXO trials. Searches of MEDLINE, EMBASE, and CINAHL Plus as well as citation searches of CRXO methodological articles were conducted to December 2014. Reporting quality was assessed against both modified items from 2010 CONSORT and 2012 cluster trials extension and other proposed quality measures. Of the 3425 records identified through database searching, 83 trials met the inclusion criteria. Trials were infrequently identified as "cluster randomis(z)ed crossover" in title (n = 7, 8%) or abstract (n = 21, 25%), and a rationale for the design was infrequently provided (n = 20, 24%). Design parameters such as the number of clusters and number of periods were well reported. Discussion of carryover took place in only 17 trials (20%). Sample size methods were only reported in 58% (n = 48) of trials. A range of approaches were used to report baseline characteristics. The analysis method was not adequately reported in 23% (n = 19) of trials. The observed within-cluster within-period intracluster correlation and within-cluster between-period intracluster correlation for the primary outcome data were not reported in any trial. The potential for selection, performance, and detection bias could be evaluated in 30%, 81%, and 70% of trials, respectively. There is a clear need to improve the quality of reporting in CRXO trials. Given the unique features of a CRXO trial, it is important to develop a CONSORT extension. Consensus amongst trialists on the content of such a guideline is essential.

Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis.

PubMed

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

2017-08-01

This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial.Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias).The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased.On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies. Copyright ©ERS 2017.

The effects of Nordic school meals on concentration and school performance in 8- to 11-year-old children in the OPUS School Meal Study: a cluster-randomised, controlled, cross-over trial.

PubMed

Sørensen, Louise B; Dyssegaard, Camilla B; Damsgaard, Camilla T; Petersen, Rikke A; Dalskov, Stine-Mathilde; Hjorth, Mads F; Andersen, Rikke; Tetens, Inge; Ritz, Christian; Astrup, Arne; Lauritzen, Lotte; Michaelsen, Kim F; Egelund, Niels

2015-04-28

It is widely assumed that nutrition can improve school performance in children; however, evidence remains limited and inconclusive. In the present study, we investigated whether serving healthy school meals influenced concentration and school performance of 8- to 11-year-old Danish children. The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study was a cluster-randomised, controlled, cross-over trial comparing a healthy school meal programme with the usual packed lunch from home (control) each for 3 months (NCT 01457794). The d2 test of attention, the Learning Rating Scale (LRS) and standard tests on reading and mathematics proficiency were administered at baseline and at the end of each study period. Intervention effects were evaluated using hierarchical mixed models. The school meal intervention did not influence concentration performance (CP; primary outcome, n 693) or processing speed; however, the decrease in error percentage was 0·18 points smaller (P<0·001) in the intervention period than in the control period (medians: baseline 2·03%; intervention 1·46%; control 1·37%). In contrast, the intervention increased reading speed (0·7 sentence, P=0·009) and the number of correct sentences (1·8 sentences, P<0·001), which corresponded to 11 and 25%, respectively, of the effect of one school year. The percentage of correct sentences also improved (P<0·001), indicating that the number correct improved relatively more than reading speed. There was no effect on overall math performance or outcomes from the LRS. In conclusion, school meals did not affect CP, but improved reading performance, which is a complex cognitive activity that involves inference, and increased errors related to impulsivity and inattention. These findings are worth examining in future trials.

Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial.

PubMed

Chu, Tanya T W; Benzie, Iris F F; Lam, Christopher W K; Fok, Benny S P; Lee, Kenneth K C; Tomlinson, Brian

2012-04-01

Previous studies have suggested that Lingzhi (Ganoderma lucidum) has antioxidant effects and possibly beneficial effects on blood pressure, plasma lipids and glucose, but these have not been confirmed in subjects with mild hypertension or hyperlipidaemia. The objective of the present study was to assess the cardiovascular, metabolic, antioxidant and immunomodulatory responses to therapy with Lingzhi in patients with borderline elevations of blood pressure and/or cholesterol in a controlled cross-over trial. A total of twenty-six patients received 1·44 g Lingzhi daily or matching placebo for 12 weeks in a randomised, double-blind, cross-over study with placebo-controlled run-in and cross-over periods. Body weight, blood pressure, metabolic parameters, urine catecholamines and cortisol, antioxidant status and lymphocyte subsets were measured after each period. Lingzhi was well tolerated and data from twenty-three evaluable subjects showed no changes in BMI or blood pressure when treated with Lingzhi or placebo. Plasma insulin and homeostasis model assessment-insulin resistance were lower after treatment with Lingzhi than after placebo. TAG decreased and HDL-cholesterol increased with Lingzhi but not with placebo in the first treatment period, but significant carry-over effects prevented complete analysis of these parameters. Urine catecholamines and cortisol, plasma antioxidant status and blood lymphocyte subsets showed no significant differences across treatments. Results indicate that Lingzhi might have mild antidiabetic effects and potentially improve the dyslipidaemia of diabetes, as shown previously in some animal studies. Further studies are desirable in patients with hyperglycaemia.

[Benefits of spironolactone as the optimal treatment for drug resistant hypertension. Pathway-2 trial review].

PubMed

Prado, J C; Ruilope, L M; Segura, J

Pathway-2 is the first randomised, double-blind and crossover trial that compares spironolactone as a fourth drug with alfa-blocker, beta-blocker and placebo. This study shows that spironolactone is the drug with more possibilities of success for the management of patients with difficult-to-treat hypertension in patients with a combination of three drugs and poor control. The results validate the widespread treatment with mineralocorticoid receptor antagonists in resistant hypertension. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

A randomised controlled trial of complete denture impression materials.

PubMed

Hyde, T P; Craddock, H L; Gray, J C; Pavitt, S H; Hulme, C; Godfrey, M; Fernandez, C; Navarro-Coy, N; Dillon, S; Wright, J; Brown, S; Dukanovic, G; Brunton, P A

2014-08-01

There is continuing demand for non-implant prosthodontic treatment and yet there is a paucity of high quality Randomised Controlled Trial (RCT) evidence for best practice. The aim of this research was to provide evidence for best practice in prosthodontic impressions by comparing two impression materials in a double-blind, randomised, crossover, controlled, clinical trial. Eighty-five patients were recruited, using published eligibility criteria, to the trial at Leeds Dental Institute, UK. Each patient received two sets of dentures; made using either alginate or silicone impressions. Randomisations determined the order of assessment and order of impressions. The primary outcome was patient blinded preference for unadjusted dentures. Secondary outcomes were patient preference for the adjusted dentures, rating of comfort, stability and chewing efficiency, experience of each impression, and an OHIP-EDENT questionnaire. Seventy-eight (91.8%) patients completed the primary assessment. 53(67.9%) patients preferred dentures made from silicone impressions while 14(17.9%) preferred alginate impressions. 4(5.1%) patients found both dentures equally satisfactory and 7 (9.0%) found both equally unsatisfactory. There was a 50% difference in preference rates (in favour of silicone) (95%CI 32.7-67.3%, p<0.0001). There is significant evidence that dentures made from silicone impressions were preferred by patients. Given the strength of the clinical findings within this paper, dentists should consider choosing silicone rather than alginate as their material of choice for secondary impressions for complete dentures. ISRCTN 01528038. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Routine blood cultures in the management of pyelonephritis in pregnancy for improving outcomes.

PubMed

Gomi, Harumi; Goto, Yoshihito; Laopaiboon, Malinee; Usui, Rie; Mori, Rintaro

2015-02-13

Pyelonephritis is a type of urinary tract infection (UTI) that affects the upper urinary tract and kidneys, and is one of the most common conditions for hospitalisation among pregnant women, aside from delivery. Samples of urine and blood are obtained and used for cultures as part of the diagnosis and management of the condition. Acute pyelonephritis requires hospitalisation with intravenous administration of antimicrobial agents. Several studies have questioned the necessity of obtaining blood cultures in addition to urine cultures, citing cost and questioning whether blood testing is superfluous. Pregnant women with bacteraemia require a change in the initial empirical treatment based on the blood culture. However, these cases are not common, and represent approximately 15% to 20% of cases. It is unclear whether blood cultures are essential for the effective management of the condition. To assess the effectiveness of routine blood cultures to improve health outcomes in the management of pyelonephritis in pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register without language or date restrictions (31 December 2014). Randomised controlled trials and quasi-randomised trials comparing outcomes among pregnant women with pyelonephritis who received initial management with or without blood cultures. Cluster-randomised trials were eligible for inclusion in this review but none were identified. Clinical trials using a cross-over design were not eligible for inclusion. Two review authors independently assessed one trial report for inclusion. We identified one trial report but this was excluded. No clinical trials met the inclusion criteria for this review. There are no large-scale randomised controlled trials to assess outcomes in the management of pyelonephritis in pregnancy with or without blood cultures. Randomised controlled trials are needed to evaluate the effectiveness of managing pyelonephritis in pregnant women with or without blood cultures, and to assess any adverse outcomes as well as the cost-effectiveness of excluding blood cultures from treatment.

EFFECT of daily antiseptic body wash with octenidine on nosocomial primary bacteraemia and nosocomial multidrug-resistant organisms in intensive care units: design of a multicentre, cluster-randomised, double-blind, cross-over study.

PubMed

Meißner, Anne; Hasenclever, Dirk; Brosteanu, Oana; Chaberny, Iris Freya

2017-11-08

Nosocomial infections are serious complications that increase morbidity, mortality and costs and could potentially be avoidable. Antiseptic body wash is an approach to reduce dermal micro-organisms as potential pathogens on the skin. Large-scale trials with chlorhexidine as the antiseptic agent suggest a reduction of nosocomial infection rates. Octenidine is a promising alternative agent which could be more effective against Gram-negative organisms. We hypothesise that daily antiseptic body wash with octenidine reduces the risk of intensive care unit (ICU)-acquired primary bacteraemia and ICU-acquired multidrug-resistant organisms (MDRO) in a standard care setting. EFFECT is a controlled, cluster-randomised, double-blind study. The experimental intervention consists in using octenidine-impregnated wash mitts for the daily routine washing procedure of the patients. This will be compared with using placebo wash mitts. Replacing existing washing methods is the only interference into clinical routine.Participating ICUs are randomised in an AB/BA cross-over design. There are two 15-month periods, each consisting of a 3-month wash-out period followed by a 12-month intervention and observation period. Randomisation determines only the sequence in which octenidine-impregnated or placebo wash mitts are used. ICUs are left unaware of what mitts packages they are using.The two coprimary endpoints are ICU-acquired primary bacteraemia and ICU-acquired MDRO. Endpoints are defined based on individual ward-movement history and microbiological test results taken from the hospital information systems without need for extra documentation. Data on clinical symptoms of infection are not collected. EFFECT aims at recruiting about 45 ICUs with about 225 000 patient-days per year. The study was approved by the ethics committee of the University of Leipzig (number 340/16-ek) in November 2016. Findings will be published in peer-reviewed journals. DRKS-ID: DRKS00011282. © 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.

Acute and second-meal effects of peanuts on glycaemic response and appetite in obese women with high type 2 diabetes risk: a randomised cross-over clinical trial.

PubMed

Reis, Caio E G; Ribeiro, Daniela N; Costa, Neuza M B; Bressan, Josefina; Alfenas, Rita C G; Mattes, Richard D

2013-06-01

Nut consumption is associated with a reduced risk of type 2 diabetes mellitus (T2DM). The aim of the present study was to assess the effects of adding peanuts (whole or peanut butter) on first (0-240 min)- and second (240-490 min)-meal glucose metabolism and selected gut satiety hormone responses, appetite ratings and food intake in obese women with high T2DM risk. A group of fifteen women participated in a randomised cross-over clinical trial in which 42·5 g of whole peanuts without skins (WP), peanut butter (PB) or no peanuts (control) were added to a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations (0-490 min) of glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), appetitive sensations and food intake were assessed after breakfast treatments and a standard lunch. Postprandial NEFA incremental AUC (IAUC) (0-240 min) and glucose IAUC (240-490 min) responses were lower for the PB breakfast compared with the control breakfast. Insulin concentrations were higher at 120 and 370 min after the PB consumption than after the control consumption. Desire-to-eat ratings were lower, while PYY, GLP-1 and CCK concentrations were higher after the PB intake compared with the control intake. WP led to similar but non-significant effects. The addition of PB to breakfast moderated postprandial glucose and NEFA concentrations, enhanced gut satiety hormone secretion and reduced the desire to eat. The greater bioaccessibility of the lipid component in PB is probably responsible for the observed incremental post-ingestive responses between the nut forms. Inclusion of PB, and probably WP, to breakfast may help to moderate glucose concentrations and appetite in obese women.

Patient participation in postoperative care activities in patients undergoing total knee replacement surgery: Multimedia Intervention for Managing patient Experience (MIME). Study protocol for a cluster randomised crossover trial.

PubMed

McDonall, Jo; de Steiger, Richard; Reynolds, John; Redley, Bernice; Livingston, Patricia; Botti, Mari

2016-07-18

Patient participation is an important indicator of quality care. Currently, there is little evidence to support the belief that participation in care is possible for patients during the acute postoperative period. Previous work indicates that there is very little opportunity for patients to participate in care in the acute context. Patients require both capability, in terms of having the required knowledge and understanding of how they can be involved in their care, and the opportunity, facilitated by clinicians, to engage in their acute postoperative care. This cluster randomised crossover trial aims to test whether a multimedia intervention improves patient participation in the acute postoperative context, as determined by pain intensity and recovery outcomes. A total of 240 patients admitted for primary total knee replacement surgery will be invited to participate in a cluster randomised, crossover trial and concurrent process evaluation in at least two wards at a major non-profit private hospital in Melbourne, Australia. Patients admitted to the intervention ward will receive the multimedia intervention daily from Day 1 to Day 5 (or day of discharge, if prior). The intervention will be delivered by nurses via an iPad™, comprising information on the goals of care for each day following surgery. Patients admitted to the control ward will receive usual care as determined by care pathways currently in use across the organization. The primary endpoint is the "worst pain experienced in the past 24 h" on Day 3 following TKR surgery. Pain intensity will be measured using the numerical rating scale. Secondary outcomes are interference of pain on activities of daily living, length of stay in hospital, function and pain following TKR surgery, overall satisfaction with hospitalisation, postoperative complications and hospital readmission. The results of this study will contribute to our understanding of the effectiveness of interventions that provide knowledge and opportunity for patient participation during postoperative in-hospital care in actually increasing participation, and the impact of participation on patient outcomes. The results of this study will also provide data about the barriers and enablers to participation in the acute care context. Australian New Zealand Clinical Trials Registry ACTRN12614000340639 Trial Registration date 31/03/2014.

A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects.

PubMed

Jin, Y; Alimbetov, D; George, T; Gordon, M H; Lovegrove, J A

2011-07-01

To study the bioavailability of anthocyanins and the effects of a 20% blackcurrant juice drink on vascular reactivity, plasma antioxidant status and other cardiovascular disease risk markers. The study was a randomised, cross-over, double-blind, placebo-controlled acute meal study. Twenty healthy volunteers (11 females and 9 males) were recruited, and all subjects completed the study. Fasted volunteers consumed a 20% blackcurrant juice drink (250 ml) or a control drink following a low-flavonoid diet for the previous 72 h. Vascular reactivity was assessed at baseline and 120 min after juice consumption by laser Doppler imaging (LDI). Plasma and urine samples were collected periodically over an 8-h period for analysis, with a final urine sample collected at 24 h. The cross-over was performed after a 4-week washout. There were no significant effects of the 20% blackcurrant juice drink on acute measures of vascular reactivity, biomarkers of endothelial function or lipid risk factors. Consumption of the test juice caused increases in plasma vitamin C (P=0.006), and urinary anthocyanins (P<0.001). Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected. The yield of anthocyanins in urine was 0.021±0.003% of the dietary intake of delphinidin glycosides and 0.009±0.002% of the dietary intake of cyanidin glycosides. The juice consumption did not have a significant effect on vascular reactivity. Anthocyanins were present at low concentrations in the urine, and microbial metabolites of flavonoids were detected in plasma after juice consumption.

Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis

PubMed Central

Wiles, C; Newcombe, R; Fuller, K; Shaw, S; Furnival-Doran, J; Pickersgill, T; Morgan, A

2001-01-01

OBJECTIVES—To determine whether physiotherapy can improve mobility in chronic multiple sclerosis and whether there is a difference between treatment at home and as a hospital outpatient?
METHODS—A randomised controlled crossover trial was undertaken in patients with chronic multiple sclerosis who had difficulty walking and were referred from neurology clinics: allocation was to one of six permutations of three 8 week treatment periods separated by 8 week intervals: treatments consisted of physiotherapy at home, as an outpatient, or "no therapy". The main outcome measures were based on independent assessments at home and included mobility related disability (primary outcome: the Rivermead mobility index), gait impairments, arm function, mood, and subjective patient and carer ratings. Therapy was assessed by recording delivery, achievement of set targets, patient and carer preference, and cost.
RESULTS—On the Rivermead mobility index (scale 0-15) (primary outcome) there was a highly significant (p<0.001) treatment effect of 1.4-1.5 units favouring hospital or home based therapy over no therapy: this was supported by other measures of mobility, gait, balance, and the assessor's global "mobility change" score: there was no major difference between home and hospital. Carers preferred home treatment but neither they nor patients discerned greater benefit there. Estimated costs of home physiotherapy were £25/session and those at hospital were £18 (including £7 patient travel costs).
CONCLUSION—A course of physiotherapy is associated with improved mobility, subjective wellbeing, and improved mood in chronic multiple sclerosis compared with no treatment but benefit may only last a few weeks: there is little to choose between home and hospital based therapy but the first is more costly, mainly due to skilled staff travelling time.

 PMID:11160464

Prolonged remission from hepatic encephalopathy with rifaximin: results of a placebo crossover analysis.

PubMed

Bajaj, J S; Barrett, A C; Bortey, E; Paterson, C; Forbes, W P

2015-01-01

Rifaximin therapy reduced risk of hepatic encephalopathy (HE) recurrence and HE-related hospitalisations during a 6-month, randomised, placebo-controlled trial (RCT) and a 24-month open-label maintenance (OLM) study. However, the impact of crossover from placebo to rifaximin therapy is unclear. To study the impact of crossing over from placebo to rifaximin treatment on breakthrough HE and hospitalisation rates using a within-subjects design. Adults with cirrhosis and history of overt HE episodes, currently in HE remission, received placebo during the RCT and crossed over to rifaximin 550 mg twice daily during the OLM study. Rate of breakthrough overt HE episodes, hospitalisations and incidence and rate of adverse events (AEs) were analysed during RCT and first 6 months of OLM. Of 82 patients randomised to placebo in the RCT who crossed over to the OLM study, 39 experienced an HE episode during the RCT compared with 14 during the OLM study (P < 0.0001). Significantly lower rates of HE events were observed with rifaximin treatment compared with placebo treatment (P < 0.0001). Rates of HE-related hospitalisation were numerically lower during rifaximin treatment compared with placebo treatment, although not significant. Rates of most common AEs, serious AEs and infection-related AEs were similar between the two treatments. This analysis confirms the repeatability of results from the RCT on safety and efficacy of rifaximin 550 mg twice daily in reducing the risk of hepatic encephalopathy recurrence, and suggests these findings are translatable outside of a rigorous, controlled trial setting. © 2014 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

PubMed

Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

2018-01-01

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (P<0·001) and Faecalibacterium (P=0·010) and decreases in Coprococcus (P=0·010), Dorea (P=0·043) and Ruminococcus (Lachnospiraceae family) (P=0·032). This study demonstrates that those with HDF intakes have a greater gut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

Effects of chronic consumption of fruit and vegetable puree-based drinks on vasodilation, plasma oxidative stability and antioxidant status.

PubMed

George, T W; Paterson, E; Waroonphan, S; Gordon, M H; Lovegrove, J A

2012-10-01

Fruit and vegetable-rich diets are associated with a reduced cardiovascular disease (CVD) risk. This protective effect may be a result of the phytochemicals present within fruits and vegetables (F&V). However, there can be considerable variation in the content of phytochemical composition of whole F&V depending on growing location, cultivar, season and agricultural practices, etc. Therefore, the present study investigated the effects of consuming fruits and vegetables as puree-based drinks (FVPD) daily on vasodilation, phytochemical bioavailability, antioxidant status and other CVD risk factors. FVPD was chosen to provide a standardised source of F&V material that could be delivered from the same batch to all subjects during each treatment arm of the study. Thirty-nine subjects completed the randomised, controlled, cross-over dietary intervention. Subjects were randomised to consume 200 mL of FVPD (or fruit-flavoured control), daily for 6 weeks with an 8-week washout period between treatments. Dietary intake was measured using two 5-day diet records during each cross-over arm of the study. Blood and urine samples were collected before and after each intervention and vasodilation assessed in 19 subjects using laser Doppler imaging with iontophoresis. FVPD significantly increased dietary vitamin C and carotenoids (P < 0.001), and concomitantly increased plasma α- and β-carotene (P < 0.001) with a near-significant increase in endothelium-dependent vasodilation (P = 0.060). Overall, the findings obtained in the present study showed that FVPD were a useful vehicle to increase fruit and vegetable intake, significantly increasing dietary and plasma phytochemical concentrations with a trend towards increased endothelium-dependent vasodilation. © 2012 The Authors Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.

Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

PubMed

Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

2016-01-01

Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.

A randomised, crossover study on an electronic vapour product, a nicotine inhalator and a conventional cigarette. Part B: Safety and subjective effects.

PubMed

Walele, Tanvir; Sharma, Girish; Savioz, Rebecca; Martin, Claire; Williams, Josie

2016-02-01

An Electronic Vapour Product (EVP) has been evaluated for short-term safety parameters and subjective effects in a 2-part study, in smokers. Part 1 compared the EVP with unflavoured (UF) and flavoured (FL) e-liquid at 2.0% nicotine to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette(®), 15 mg). Part 2 assessed the effect of increasing concentrations of nicotine in the e-liquid used with the EVP (0%, 0.4%, 0.9%, 2.0%). The study was designed as a randomised, controlled, crossover trial. Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms. In both study parts, only mild non-serious AEs were reported. No major differences were observed in AEs between the EVPs and Nicorette(®). Exhaled CO levels only increased for CC. All products appeared to decrease smoking urges and nicotine withdrawal symptom scores to a similar extent. The EVP had a similar short-term safety profile to Nicorette(®) and relieved smoking urges and nicotine withdrawal symptoms to a similar extent as Nicorette(®) and CC. Unlike nicotine replacement therapies, the EVP may offer an alternative for those finding it difficult to quit the behavioural and sensorial aspects of smoking. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of lacosamide on the steady-state pharmacokinetics of digoxin: results from a phase I, multiple-dose, double-blind, randomised, placebo-controlled, crossover trial.

PubMed

Cawello, Willi; Mueller-Voessing, Christa; Andreas, Jens-Otto

2014-05-01

Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide. To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of digoxin administered in combination with lacosamide or placebo. Twenty healthy White male volunteers were randomised. After receiving digoxin 0.25 mg three times daily on day 1 (loading dose), participants received digoxin 0.25 mg once daily on days 2-22. Participants received either lacosamide (200 mg twice daily) or placebo on days 8-11 and vice versa on days 18-21, after a 6-day washout. The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum steady-state plasma concentration (C(max,ss)) of digoxin were measured; ratios of these parameters for co-administration of digoxin + lacosamide versus digoxin alone were used to evaluate potential DDIs. Interaction was excluded if the 90 % confidence interval (CI) for the geometric mean ratio of AUC24,ss and C max,ss fell within the acceptance range for bioequivalence (0.8-1.25). The point estimates (90 % CI) of the geometric mean ratios for co-administration of digoxin with lacosamide versus digoxin alone for AUC(24,ss) [1.024 (0.979-1.071)] and C(max,ss) [1.049 (0.959-1.147)] were within the acceptance range for bioequivalence. Digoxin and lacosamide co-administration was generally well-tolerated. A small numerical increase in the mean PR interval following co-administered digoxin + lacosamide was observed versus digoxin alone and versus pre-treatment baseline values (178.5 vs. 170.4 or 166.8 ms, respectively). The RR interval increased in parallel. The change was not considered clinically relevant. Co-administration of steady-state digoxin (0.25 mg/day) with multiple-dose lacosamide (400 mg/day) versus digoxin alone revealed no differences in digoxin disposition.

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO).

PubMed

Quinnell, Timothy G; Bennett, Maxine; Jordan, Jake; Clutterbuck-James, Abigail L; Davies, Michael G; Smith, Ian E; Oscroft, Nicholas; Pittman, Marcus A; Cameron, Malcolm; Chadwick, Rebecca; Morrell, Mary J; Glover, Matthew J; Fox-Rushby, Julia A; Sharples, Linda D

2014-10-01

Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5-<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20,000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39,800/QALY. Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice. ISRCTN02309506. 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.

Augmented-reality-based skills training for robot-assisted urethrovesical anastomosis: a multi-institutional randomised controlled trial.

PubMed

Chowriappa, Ashirwad; Raza, Syed Johar; Fazili, Anees; Field, Erinn; Malito, Chelsea; Samarasekera, Dinesh; Shi, Yi; Ahmed, Kamran; Wilding, Gregory; Kaouk, Jihad; Eun, Daniel D; Ghazi, Ahmed; Peabody, James O; Kesavadas, Thenkurussi; Mohler, James L; Guru, Khurshid A

2015-02-01

To validate robot-assisted surgery skills acquisition using an augmented reality (AR)-based module for urethrovesical anastomosis (UVA). Participants at three institutions were randomised to a Hands-on Surgical Training (HoST) technology group or a control group. The HoST group was given procedure-based training for UVA within the haptic-enabled AR-based HoST environment. The control group did not receive any training. After completing the task, the control group was offered to cross over to the HoST group (cross-over group). A questionnaire administered after HoST determined the feasibility and acceptability of the technology. Performance of UVA using an inanimate model on the daVinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) was assessed using a UVA evaluation score and a Global Evaluative Assessment of Robotic Skills (GEARS) score. Participants completed the National Aeronautics and Space Administration Task Load Index (NASA TLX) questionnaire for cognitive assessment, as outcome measures. A Wilcoxon rank-sum test was used to compare outcomes among the groups (HoST group vs control group and control group vs cross-over group). A total of 52 individuals participated in the study. UVA evaluation scores showed significant differences in needle driving (3.0 vs 2.3; P = 0.042), needle positioning (3.0 vs 2.4; P = 0.033) and suture placement (3.4 vs 2.6; P = 0.014) in the HoST vs the control group. The HoST group obtained significantly higher scores (14.4 vs 11.9; P 0.012) on the GEARS. The NASA TLX indicated lower temporal demand and effort in the HoST group (5.9 vs 9.3; P = 0.001 and 5.8 vs 11.9; P = 0.035, respectively). In all, 70% of participants found that HoST was similar to the real surgical procedure, and 75% believed that HoST could improve confidence for carrying out the real intervention. Training in UVA in an AR environment improves technical skill acquisition with minimal cognitive demand. © 2014 The Authors. BJU International © 2014 BJU International.

Effect of dietary prebiotic supplementation on advanced glycation, insulin resistance and inflammatory biomarkers in adults with pre-diabetes: a study protocol for a double-blind placebo-controlled randomised crossover clinical trial.

PubMed

Kellow, Nicole J; Coughlan, Melinda T; Savige, Gayle S; Reid, Christopher M

2014-07-10

Advanced glycation endproducts (AGEs) contribute to the development of vascular complications of diabetes and have been recently implicated in the pathogenesis of diabetes. Since AGEs are generated within foodstuffs upon food processing, it is increasingly recognised that the modern diet is replete with AGEs. AGEs are thought to stimulate chronic low-grade inflammation and promote oxidative stress and have been linked to the development of insulin resistance. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of type 2 diabetes in susceptible individuals. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host, but its effect on advanced glycation is unknown. The aim of this article is to describe the methodology of a double-blind placebo-controlled randomised crossover trial designed to determine the effect of 12 week consumption of a prebiotic dietary supplement on the advanced glycation pathway, insulin sensitivity and chronic low-grade inflammation in adults with pre-diabetes. Thirty adults with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) aged between 40-60 years will be randomly assigned to receive either 10 grams of prebiotic (inulin/oligofructose) daily or 10 grams placebo (maltodextrin) daily for 12 weeks. After a 2-week washout period, study subjects will crossover to receive the alternative dietary treatment for 12 weeks. The primary outcome is the difference in markers of the advanced glycation pathway carboxymethyllysine (CML) and methylglyoxal (MG) between experimental and control treatments. Secondary outcomes include HbA1c, insulin sensitivity, lipid levels, blood pressure, serum glutathione, adiponectin, IL-6, E-selectin, myeloperoxidase, C-reactive protein, Toll-like Receptor 4 (TLR4), soluble receptor for AGE (sRAGE), urinary 8-isoprostanes, faecal bacterial composition and short chain fatty acid profile. Anthropometric measures including BMI and waist circumference will be collected in addition to comprehensive dietary and lifestyle data. Prebiotics which selectively stimulate the growth of beneficial bacteria in the human colon might offer protection against AGE-related pathology in people at risk of developing type 2 diabetes. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000130763.

Effect of a change to mite-free bedding on children with mite-sensitive asthma: a controlled trial.

PubMed Central

Burr, M L; Neale, E; Dean, B V; Verrier-Jones, E R

1980-01-01

Twenty-one children with mite-sensitive asthma took part in a crossover randomised controlled trial of mite-free bedding. Each child was issued with a new sleeping bag and pillow for a month, and twice-daily peak flow readings were compared with those obtained during a month in the child's ordinary bedding. Seventeen of the children had higher mean peak flow readings during the period in the mite-free bedding (p < 0.01). The overall improvement was only modest, however, and some mites had appeared in most of the bedding by the end of the trial. New bedding may be helpful to patients with mite-sensitive asthma, but methods are needed to prevent colonisation by mites. PMID:7001668

Talcum powder or aqueous gel to aid external cephalic version: a randomised controlled trial

PubMed Central

2014-01-01

Background External cephalic version (ECV) is offered to reduce the number of Caesarean delivery indicated by breech presentation which occurs in 3-4% of term pregnancies. ECV is commonly performed aided by the application of aqueous gel or talcum powder to the maternal abdomen. We sought to compare gel with powder during ECV on achieving successful version and increasing tolerability. Method We enrolled 95 women (≥ 36 weeks gestation) on their attendance for planned ECV. All participants received terbutaline tocolysis. Regional anaesthesia was not used. ECV was performed in the standard fashion after the application of the allocated aid. If the first round (maximum of 2 attempts) of ECV failed, crossover to the opposing aid was permitted. Results 48 women were randomised to powder and 47 to gel. Self-reported procedure related median [interquartile range] pain scores (using a 10-point visual numerical rating scale VNRS; low score more pain) were 6 [5-9] vs. 8 [7-9] P = 0.03 in favor of gel. ECV was successful in 21/48 (43.8%) vs. 26/47 (55.3%) RR 0.6 95% CI 0.3-1.4 P = 0.3 for powder and gel arms respectively. Crossover to the opposing aid and a second round of ECV was performed in 13/27 (48.1%) following initial failure with powder and 4/21 (19%) after failure with gel (RR 3.9 95% CI 1.0-15 P = 0.07). ECV success rate was 5/13 (38.5%) vs. 1/4 (25%) P = 0.99 after crossover use of gel or powder respectively. Operators reported higher satisfaction score with the use of gel (high score, greater satisfaction) VNRS scores 6 [4.25-8] vs 8 [7-9] P = 0.01. Conclusion Women find gel use to be associated with less pain. The ECV success rate is not significantly different. Trial registration The trial is registered with ISRCTN (identifier ISRCTN87231556). PMID:24468078

The IDEAL study : towards personalized drug treatment of hypertension.

PubMed

Bejan-Angoulvant, Theodora; Baguet, Jean-Philippe; Erpeldinger, Sylvie; Boivin, Jean-Marc; Mercier, Alain; Leftheriotis, Georges; Gagnol, Jean-Pierre; Fauvel, Jean-Pierre; Giraud, Céline; Bricca, Giampiero; Gueyffier, François

2012-01-01

To identify markers (phenotypic, genetic, or environmental) of blood pressure (BP) response profiles to angiotensin converting enzyme inhibitors (ACEIs) and diuretics. IDEAL was a crossover (two active and two wash out phases), double-blind, placebo-controlled trial. Eligible patients were untreated hypertensive, aged 25 to 70. After two visits, patients were randomized to one of four sequences. The main outcome was BP differences between the active treatment and placebo. One hundred and twenty-four patients were randomised: mean age 53, men 65%, family history of hypertension 60%. Average BP fall at each visit before randomisation was about 2% of the initial level reflecting both a regression to the mean and a placebo effect. The results are expected to improve knowledge in drug's mechanisms of action and pathophysiology of hypertension, and to help in personalizing treatment. The estimation of BP responses to each drug in standardized conditions provided a benefit to each participant. © 2012 Société Française de Pharmacologie et de Thérapeutique.

A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial): study rationale and design

PubMed Central

2012-01-01

Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996. PMID:22727048

Asperger syndrome and anxiety disorders (PAsSA) treatment trial: a study protocol of a pilot, multicentre, single-blind, randomised crossover trial of group cognitive behavioural therapy

PubMed Central

Langdon, Peter E; Murphy, Glynis H; Wilson, Edward; Shepstone, Lee; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra

2013-01-01

Introduction A number of studies have established that children, adolescents and adults with Asperger syndrome (AS) and high functioning autism (HFA) have significant problems with anxiety. Cognitive behavioural therapy (CBT) is an effective treatment for anxiety in a variety of clinical populations. There is a growing interest in exploring the effectiveness of CBT for people with AS who have mental health problems, but currently there are no known clinical trials involving adults with AS or HFA. Studies with children who have AS have reported some success. The current study aims to examine whether modified group CBT for clinically significant anxiety in an AS population is likely to be efficacious. Methods and analysis This study is a randomised, single-blind crossover trial. At least 36 individuals will be recruited and randomised into a treatment arm or a waiting-list control arm. During treatment, individuals will receive 3 sessions of individual CBT, followed by 21 sessions of group CBT. Primary outcome measures focus on anxiety. Secondary outcome measures focus on everyday social and psychiatric functioning, additional measures of anxiety and fear, depression, health-related quality of life and treatment cost. Assessments will be administered at pregroup and postgroup and at follow-up by researchers who are blinded to group allocation. The trial aims to find out whether or not psychological treatments for anxiety can be adapted and used to successfully treat the anxiety experienced by people with AS. Furthermore, we aim to determine whether this intervention represents good value for money. Ethics and dissemination The trial received a favourable ethical opinion from a National Health Service (NHS) Research Ethics Committee. All participants provided written informed consent. Findings will be shared with all trial participants, and the general public, as well as the scientific community. Trial Registration ISRCTN 30265294 (DOI: 10.1186/ISRCTN30265294), UKCRN 8370. PMID:23901031

Examining the effectiveness of consuming flour made from agronomically biofortified wheat (Zincol-2016/NR-421) for improving Zn status in women in a low-resource setting in Pakistan: study protocol for a randomised, double-blind, controlled cross-over trial (BiZiFED).

PubMed

Lowe, Nicola M; Khan, Muhammad Jaffar; Broadley, Martin R; Zia, Munir H; McArdle, Harry J; Joy, Edward J M; Ohly, Heather; Shahzad, Babar; Ullah, Ubaid; Kabana, Gul; Medhi, Rashid; Afridi, Mukhtiar Zaman

2018-04-17

Dietary zinc (Zn) deficiency is a global problem, particularly in low-income and middle-income countries where access to rich, animal-source foods of Zn is limited due to poverty. In Pakistan, Zn deficiency affects over 40% of the adult female population, resulting in suboptimal immune status and increased likelihood of complications during pregnancy. We are conducting a double-blind, randomised controlled feeding study with cross-over design in a low-resource setting in Pakistan. Households were provided with flour milled from genetically and agronomically biofortified grain (Zincol-2016/NR-421) or control grain (Galaxy-2013). Fifty households were recruited. Each household included a woman aged 16-49 years who is neither pregnant nor breastfeeding, and not currently consuming nutritional supplements. These women were the primary study participants. All households were provided with control flour for an initial 2-week baseline period, followed by an 8-week intervention period where 25 households receive biofortified flour (group A) and 25 households receive control flour (group B). After this 8-week period, groups A and B crossed over, receiving control and biofortified flour respectively for 8 weeks. Tissue (blood, hair and nails) have been collected from the women at five time points: baseline, middle and end of period 1, and middle and end of period 2. Ethical approval was granted from the lead university (reference no. STEMH 697 FR) and the collaborating institution in Pakistan. The final study methods (including any modifications) will be published in peer-reviewed journals, alongside the study outcomes on completion of the data analysis. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum. The trial has been registered with the ISRCTN registry, study ID ISRCTN83678069. © 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.

Eradication of early P. aeruginosa infection in children <7 years of age with cystic fibrosis: The early study.

PubMed

Ratjen, Felix; Moeller, Alexander; McKinney, Martha L; Asherova, Irina; Alon, Nipa; Maykut, Robert; Angyalosi, Gerhild

2018-04-20

Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited. This double-blind, placebo-controlled trial randomised CF patients <7 years (N = 51) with early Pa-infection to tobramycin inhalation solution (TOBI 300 mg) or placebo (twice daily) for 28 days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29. On Day 29, 84.6% patients in the TOBI versus 24.0% in the placebo group were Pa-free (p < 0.001). At the end of the cross-over period, 76.0% patients receiving TOBI in the initial 28 days were Pa-free compared to 47.8% receiving placebo initially. Adverse events were consistent with the TOBI safety profile with no differences between TOBI and placebo. TOBI was effective in eradicating early Pa-infection with a favourable safety profile in young CF patients. NCT01082367. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

The effects of a combined static-dynamic stretching protocol on athletic performance in elite Gaelic footballers: A randomised controlled crossover trial.

PubMed

Loughran, Martin; Glasgow, Philip; Bleakley, Chris; McVeigh, Joseph

2017-05-01

To determine the effect of three different static-dynamic stretching protocols on sprint and jump performance in Gaelic footballers. Double-blind, controlled, crossover trial. Sports Institute research environment. Seventeen male elite level Gaelic footballers, aged 18-30 years, completed three stretching protocols. Athletic performance was measured by countermovement jump height and power, and timed 10 m, 20 m, and 40 m sprints. Static stretching reduced sprint speed by 1.1% over 40 m and 1.0% over 20 m. Static stretching also reduced countermovement jump height by 10.6% and jump power by 6.4%. When static stretching was followed by dynamic stretching, sprint speed improved by 1.0% over 20 m and 0.7% over 40 m (p < 0.05). The static - dynamic stretching protocol also improved countermovement jump height by 8.7% (p < 0.01) and power by 6.7% (p < 0.01). Static stretching reduces sprint speed and jump performance. Static stretching should be followed by dynamic stretching during warm-up to nullify any performance deficits caused by static stretching. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of hand-training in persons with myotonic dystrophy type 1--a randomised controlled cross-over pilot study.

PubMed

Aldehag, Anna; Jonsson, Hans; Lindblad, Jan; Kottorp, Anders; Ansved, Tor; Kierkegaard, Marie

2013-10-01

To investigate the effects of a hand-training programme on grip, pinch and wrist force, manual dexterity and activities of daily living, in adults with myotonic dystrophy type 1 (DM1). In this randomised controlled trial with a crossover design, 35 adults with DM1 were, after stratification for grip force, assigned by lot to two groups. Group A started with 12 weeks of hand training, while group B had no intervention. After a wash-out period of 12 weeks, where none received training, the order was reversed. The Grippit® was used as primary outcome measure and the hand-held Microfet2™ myometer, the Purdue Pegboard, the Canadian Occupational Performance Measure (COPM) and the Assessment of Motor and Process Skills (AMPS) were secondary outcome measures. Assessments were performed before and after training and control periods, i.e. four times altogether. Ten persons dropped out and 13 had acceptable adherence. Intention-to-treat analyses revealed significant intervention effects for isometric wrist flexor force (p = 0.048), and for COPM performance (p = 0.047) and satisfaction (p = 0.027). On an individual level, improvements were in general showed after a training period. The hand-training programme had positive effects on wrist flexor force and self-perception of occupational performance, and of satisfaction with performance. No evident detrimental effects were shown. Myotonic dystrophy type 1 (DM1) is a slowly progressive neuromuscular disease characterised by myotonia and muscle weakness and wasting. People with DM1 are often concerned about their ability to carry out ADL and to participate in, e.g. work, sports and hobbies when they gradually become weaker. This pilot study showed that a hand-training programme improved wrist flexor force and self-perception and satisfaction of occupational performance. Resistance training of hand muscles with a silicon-based putty can be a therapy option for people with DM1 in clinical practise.

The effectiveness of healthy meals at work on reaction time, mood and dietary intake: a randomised cross-over study in daytime and shift workers at an university hospital.

PubMed

Leedo, Eva; Beck, Anne Marie; Astrup, Arne; Lassen, Anne D

2017-07-01

Our dietary habits affect both cognitive performance and mood. The aim of the study was to examine the effect of increased availability of healthy meals and water at work on healthcare staff. The study used an 8-week randomised cross-over design. A total of sixty physicians, nurses and nursing assistants, including sixteen working on shifts, were recruited. The participants received a self-selected keyhole-labelled (Nordic nutrition label) lunch, snack and bottled water during each shift throughout the intervention period. Reaction time (Go/No-Go test), mood-related scores (POMS) and dietary intake were assessed at run-in, and at the end of the intervention and the control periods. The intake of fat (P=0·030) and PUFA (P=0·003) was lower, and the intake of carbohydrate (P=0·008), dietary fibre (P=0·031) and water (P<0·001) was greater in the intervention period than in the control period. The intervention had no effect on reaction time or any of the mood-related scores in the group as a whole. In shift-working participants, the intervention period resulted in a 31·1 % lower Fatigue-Inertia Score (P=0·003), a 15·3 % higher Vigour-Activity Score (P=0·041) and a 42·7 % lower Total Mood Disturbance Score (P=0·017), whereas the only dietary component that significantly improved was water intake (P=0·034), when compared with the control period. Providing healthy meals, snacks and water during working hours seems to be an effective way of improving employees' dietary intake. Moreover, increased intake of water may be associated with beneficial effects on fatigue, vigour and total mood in shift-working healthcare staff.

Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis

PubMed Central

Balfour-Lynn, I.; Klein, N.; Dinwiddie, R.

1997-01-01

Accepted 29 April 1997
 BACKGROUND—Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis.
OBJECTIVE—To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis.
DESIGN—Double blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 µg/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover.
OUTCOME MEASURES—Sputum inflammatory markers (interleukin-8, tumour necrosis factor-α (TNF-α) and neutrophil elastase—both free and bound to α1-antiprotease), sputum interleukin-10, lung function, and symptomatology.
SUBJECTS—Twenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV1) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol.
RESULTS—No significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of placebo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment.
CONCLUSIONS—Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy.

 PMID:9301350

Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover study.

PubMed

Mathers, M J; Klotz, T; Roth, S; Lümmen, G; Sommer, F

2009-06-01

We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0-8 (0 = almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT) was measured. Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg). After a wash-out phase for 1 week, medication was changed in a cross-over design. Initially, all 72 men with PE received behavioural therapy. Twenty-three men were satisfied with treatment and excluded. The remaining 49 men graded their PE as 5.94 +/- 1.6 and IELT was 0.59 min and patients were randomised. Four men discontinued the study. Vardenafil improved PE grading: 2.7 +/- 2.1 (P < 0.01) and IELT increased to 5.01 +/- 3.69 (P < 0.001). PE grading improved 1.92 +/- 1.32, (P < 0.01) and IELT 3.12 +/- 1.89 (P < 0.001) with sertraline. It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE.

A randomised control trial of walking to ameliorate brain injury fatigue: a NIDRR TBI model system centre-based study.

PubMed

Kolakowsky-Hayner, Stephanie A; Bellon, Kimberly; Toda, Ketra; Bushnik, Tamara; Wright, Jerry; Isaac, Linda; Englander, Jeffrey

2017-10-01

Fatigue is one of the most commonly reported sequelae after traumatic brain injury (TBI). This study evaluated the impact of a graduated physical activity programme on fatigue after TBI. Using a prospective randomised single-blind crossover design, 123 individuals with TBI, over the age of 18, were enrolled. Interventions included a home-based walking programme utilising a pedometer to track daily number of steps at increasing increments accompanied by tapered coaching calls over a 12-week period. Nutritional counselling with the same schedule of coaching calls served as the control condition. Main outcome measures included: the Global Fatigue Index (GFI), the Barrow Neurological Institute (BNI) Fatigue Scale Overall Severity Index Score, and the Multidimensional Fatigue Inventory (MFI). Step counts improved over time regardless of group assignment. The walking intervention led to a decrease in GFI, BNI Total, and MFI General scores. Participants reported less fatigue at the end of the active part of the intervention (24 weeks) and after a wash out period (36 weeks) as measured by the BNI Overall. The study suggests that walking can be used as an efficient and cost-effective tool to improve fatigue in persons who have sustained a TBI.

Indacaterol and glycopyrronium versus indacaterol on body plethysmography measurements in COPD-a randomised controlled study.

PubMed

Salomon, Joerg; Stolz, Daiana; Domenighetti, Guido; Frey, Jean-Georges; Turk, Alexander J; Azzola, Andrea; Sigrist, Thomas; Fitting, Jean-William; Schmidt, Ulrich; Geiser, Thomas; Wild, Corinne; Kostikas, Konstantinos; Clemens, Andreas; Brutsche, Martin

2017-01-11

Dual bronchodilator therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD). There are limited data on effects of a combination of two long-acting bronchodilators on lung function including body plethysmography. This multicentre, randomised, double-blind, single-dose, cross-over, placebo-controlled study evaluated efficacy and safety of the free combination of indacaterol maleate (IND) and glycopyrronium bromide (GLY) versus IND alone on spirometric and body plethysmography parameters, including inspiratory capacity (IC), forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), total lung capacity (TLC) and airway resistance (Raw) in moderate-to-severe COPD patients. Seventy-eight patients with FEV 1 % pred. (mean ± SD) 56 ± 13% were randomised. The combination of IND + GLY versus IND presented a numerically higher peak-IC (Δ = 0.076 L, 95% confidence interval [CI]: -0.010 - 0.161 L; p = 0.083), with a statistically significant difference in mean IC over 4 h (Δ = 0.054 L, 95%CI 0.022 - 0.086 L; p = 0.001). FEV 1 , FVC and Raw, but not TLC, were consistently significantly improved by IND + GLY compared to IND alone. Safety profiles of both treatments were comparable. The free combination of IND + GLY improved lung function parameters as evaluated by spirometry and body plethysmography, with a similar safety profile compared to IND alone. NCT01699685.

Effects of tetrahydrocannabinol on balance and gait in patients with dementia: A randomised controlled crossover trial.

PubMed

van den Elsen, Geke Ah; Tobben, Lieke; Ahmed, Amir Ia; Verkes, Robbert Jan; Kramers, Cornelis; Marijnissen, Radboud M; Olde Rikkert, Marcel Gm; van der Marck, Marjolein A

2017-02-01

Oral tetrahydrocannabinol (THC) is currently studied for its possible efficacy on dementia-related neuropsychiatric symptoms (NPS), but might lead to increased risk of falling. This was a randomised, double-blind, crossover study to evaluate the effects of THC on mobility in dementia patients. Eighteen community-dwelling patients ( M age =77 years) received 1.5 mg of oral THC twice daily and placebo, in random order, for three days, separated by a four-day washout. Balance and gait were assessed using SwayStar TM and GAITRite TM within two hours after administration, in two consecutive intervention periods, under the following conditions: standing with eyes open (EO) and eyes closed (EC), preferred speed walking with and without a cognitive dual task. THC significantly increased sway during standing EC (roll angle 0.32[±0.6]°, p=0.05; pitch angle 1.04[±1.5]°, p=0.009; pitch velocity 1.96[±3.3]°/s, p=0.02), but not during standing EO. During preferred speed walking, THC increased stride length (4.3[±5.4] cm, p=0.005) and trunk sway (pitch angle 1.18[±1.6]°, p=0.005). No effects were observed during dual task walking. No differences in the number and type of adverse events were found, and no falls occurred after administration of THC. This study showed that 3 mg of THC per day has a benign adverse event profile regarding mobility and was well tolerated by community-dwelling dementia patients.

Nasal continuous positive airway pressure: does bubbling improve gas exchange?

PubMed

Morley, C J; Lau, R; De Paoli, A; Davis, P G

2005-07-01

In a randomised crossover trial, 26 babies, treated with Hudson prong continuous positive airway pressure (CPAP) from a bubbling bottle, received vigorous, high amplitude, or slow bubbling for 30 minutes. Pulse oximetry, transcutaneous carbon dioxide, and respiratory rate were recorded. The bubbling rates had no effect on carbon dioxide, oxygenation, or respiratory rate.

Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study

USDA-ARS?s Scientific Manuscript database

Modifying microbiota towards a 'beneficial' composition is a promising approach for improving intestinal as well as overall health. Natural fibers and phytochemicals that reach the proximal colon, such as those present in various nuts, provide substrates for maintaining a healthy and diverse microbi...

Hydrophilic-coated catheters for intermittent catheterisation reduce urethral micro trauma: a prospective, randomised, participant-blinded, crossover study of three different types of catheters.

PubMed

Stensballe, J; Looms, D; Nielsen, P N; Tvede, M

2005-12-01

To compare two hydrophilic-coated (SpeediCath and LoFric and one uncoated gel-lubricated catheter (InCare Advance Plus) concerning withdrawal friction force and urethral micro trauma. 49 healthy male volunteers participated in this prospective, randomised, blinded, crossover study of three different bladder catheters. The withdrawal friction force was measured, and urine analysis of blood, nitrite and leucocytes, microbiological analysis of urine cultures and subjective evaluation of the catheters were performed. 40 participants completed the study and were included in the analysis. SpeediCath exerted a significantly lower mean withdrawal friction force and work than the gel-lubricated uncoated catheter, whereas LoFric exerted a significantly higher mean friction force than both of the other catheters. The hydrophilic catheters caused less microscopic haematuria and less pain than the gel-lubricated uncoated catheter. Furthermore, 93% of the participants preferred the hydrophilic catheters. Hydrophilic-coated catheters perform better than uncoated catheters with regard to haematuria and preference. SpeediCath, but not LoFric, exerts less withdrawal friction force than InCare Advance Plus.

Systematic review and meta-analysis of randomised controlled trials on the effects of potassium supplements on serum potassium and creatinine.

PubMed

Cappuccio, Francesco P; Buchanan, Laura A; Ji, Chen; Siani, Alfonso; Miller, Michelle A

2016-08-26

High potassium intake could prevent stroke, but supplementation is considered hazardous. We assessed the effect of oral potassium supplementation on serum or plasma potassium levels and renal function. We updated a systematic review of the effects of potassium supplementation in randomised clinical trials carried out worldwide, published in 2013, extending it to July 2015. We followed the PRISMA guidelines. Any individual taking part in a potassium supplementation randomised clinical trial. Studies included met the following criteria: randomised clinical trials, potassium supplement given and circulating potassium levels reported. Oral potassium supplementation. Serum or plasma potassium and serum or plasma creatinine. A total of 20 trials (21 independent groups) were included (1216 participants from 12 different countries). All but 2 were controlled (placebo n=16, control n=2). Of these trials, 15 were crossover, 4 had a parallel group and 1 was sequential. The duration of supplementation varied from 2 to 24 weeks and the amount of potassium given from 22 to 140 mmol/day. In the pooled analysis, potassium supplementation caused a small but significant increase in circulating potassium levels (weighted mean difference (WMD) 0.14 mmol/L, 95% CI 0.09 to 0.19, p<1×10(-5)), not associated with dose or duration of treatment. The average increase in urinary potassium excretion was 45.75 mmol/24 hours, 95% CI 38.81 to 53.69, p<1×10(-5). Potassium supplementation did not cause any change in circulating creatinine levels (WMD 0.30 µmol/L, 95% CI -1.19 to 1.78, p=0.70). In short-term studies of relatively healthy persons, a moderate oral potassium supplement resulted in a small increase in circulating potassium levels and no change in renal function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Creatine for women in pregnancy for neuroprotection of the fetus.

PubMed

Dickinson, Hayley; Bain, Emily; Wilkinson, Dominic; Middleton, Philippa; Crowther, Caroline A; Walker, David W

2014-12-19

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury. To assess the effects of creatine when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014). We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of creatine. We identified no completed or ongoing randomised controlled trials. We found no randomised controlled trials for inclusion in this review. As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

The effect of benzocaine and ketoprofen gels on pain during fixed orthodontic appliance treatment: a randomised, double-blind, crossover trial.

PubMed

Eslamian, Ladan; Borzabadi-Farahani, Ali; Gholami, Hadi

2016-05-01

To compare the analgesic effect of topical benzocaine (5%) and ketoprofen (1.60 mg/mL) after 2 mm activation of 7 mm long delta loops used for maxillary en-masse orthodontic space closure. Twenty patients (seven males, 13 females, 15-25 years of age, mean age of 19.5 years) participated in a randomised crossover, double-blind trial. After appliance activation, participants were instructed to use analgesic gels and record pain perception at 2, 6, 24 hours and 2, 3 and 7 days (at 18.00 hrs), using a visual analogue scale ruler (VAS, 0-4). Each patient received all three gels (benzocaine, ketoprofen, and a control (placebo)) randomly, but at three different appliance activation visits following a wash-over gap of one month. After the first day, the patients were instructed to repeat gel application twice a day at 10:00 and 18:00 hrs for three days. The recorded pain scores were subjected to non-parametric analysis. The highest pain was recorded at 2 and 6 hours. Pain scores were significantly different between the three groups (Kruskal-Wallis test, p < 0.01). The overall mean (SD) pain scores for the benzocaine 5%, ketoprofen, and control (placebo) groups were 0.89 (0.41), 0.68 (0.34), and 1.15 (0.81), respectively. The pain scores were significantly different between the ketoprofen and control groups (mean difference = 0.47, p = 0.005). All groups demonstrated significant differences in pain scores at the six different time intervals (p < 0.05) and there was no gender difference (p > 0.05). A significant pain reduction was observed following the use of ketoprofen when tested against a control gel (placebo). The highest pain scores were experienced in patients administered the placebo and the lowest scores in patients who applied ketoprofen gel. Benzocaine had an effect mid-way between ketoprofen and the placebo. The highest pain scores were recorded 2 hours following force application, which decreased to the lowest scores after 7 days.

To remove or to replace traditional electronic games? A crossover randomised controlled trial on the impact of removing or replacing home access to electronic games on physical activity and sedentary behaviour in children aged 10–12 years

PubMed Central

Straker, Leon M; Abbott, Rebecca A; Smith, Anne J

2013-01-01

Objective To evaluate the impact of (1) the removal of home access to traditional electronic games or (2) their replacement with active input electronic games, on daily physical activity and sedentary behaviour in children aged 10–12 years. Design Crossover randomised controlled trial, over 6 months. Setting Family homes in metropolitan Perth, Australia from 2007 to 2010. Participants 10-year-old to 12-year-old children were recruited through school and community media. From 210 children who were eligible, 74 met inclusion criteria, 8 withdrew and 10 had insufficient primary outcome measures, leaving 56 children (29 female) for analysis. Intervention A counterbalanced randomised order of three conditions sustained for 8 weeks each: no home access to electronic games, home access to traditional electronic games and home access to active input electronic games. Main outcome measures Primary outcome was accelerometer assessed moderate/vigorous physical activity (MVPA). Secondary outcomes included sedentary time and diary assessed physical activity and sedentary behaviours. Results Daily MVPA across the whole week was not significantly different between conditions. However, compared with home access to traditional electronic games, removal of all electronic games resulted in a significant increase in MVPA (mean 3.8 min/day, 95% CI 1.5 to 6.1) and a decrease in sedentary time (4.7 min/day, 0.0 to 9.5) in the after-school period. Similarly, replacing traditional games with active input games resulted in a significant increase in MVPA (3.2 min/day, 0.9 to 5.5) and a decrease in sedentary time (6.2 min/day, 1.4 to 11.4) in the after-school period. Diary reports supported an increase in physical activity and a decrease in screen-based sedentary behaviours with both interventions. Conclusions Removal of sedentary electronic games from the child's home and replacing these with active electronic games both resulted in small, objectively measured improvements in after-school activity and sedentary time. Parents can be advised that replacing sedentary electronic games with active electronic games is likely to have the same effect as removing all electronic games. Trial Registration Australia and New Zealand Clinical Trials Registry (ACTRN 12609000279224) PMID:23818650

Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.

PubMed

Israel, Elliot; Chinchilli, Vernon M; Ford, Jean G; Boushey, Homer A; Cherniack, Reuben; Craig, Timothy J; Deykin, Aaron; Fagan, Joanne K; Fahy, John V; Fish, James; Kraft, Monica; Kunselman, Susan J; Lazarus, Stephen C; Lemanske, Robert F; Liggett, Stephen B; Martin, Richard J; Mitra, Nandita; Peters, Stephen P; Silverman, Eric; Sorkness, Christine A; Szefler, Stanley J; Wechsler, Michael E; Weiss, Scott T; Drazen, Jeffrey M

The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial. Patients with mild asthma, not using a controller medication, were enrolled in pairs matched for forced expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37; four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype. Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. Morning peak expiratory flow rate (PEFR) was the primary outcome variable. The primary comparisons were between treatment period for each genotype; the secondary outcome was a treatment by genotype effect. Analyses were by intention to treat. During the run-in period, when albuterol use was kept to a minimum, patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min (p=0.0162); the change in patients with the Gly/Gly genotype was not significant (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175). By contrast, patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period, when albuterol use was limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar genotype-specific effects in FEV1, symptoms, and use of supplementary reliever medication. Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype.

Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial.

PubMed

Karstoft, Kristian; Winding, Kamilla; Knudsen, Sine H; James, Noemi G; Scheel, Maria M; Olesen, Jesper; Holst, Jens J; Pedersen, Bente K; Solomon, Thomas P J

2014-10-01

By use of a parallel and partly crossover randomised, controlled trial design we sought to elucidate the underlying mechanisms behind the advantageous effects of interval walking training (IWT) compared with continuous walking training (CWT) on glycaemic control in individuals with type 2 diabetes. We hypothesised that IWT, more than CWT, would improve insulin sensitivity including skeletal muscle insulin signalling, insulin secretion and disposition index (DI). By simple randomisation (sequentially numbered, opaque sealed envelopes), eligible individuals (diagnosed with type 2 diabetes, no exogenous insulin treatment) were allocated to three groups: a control group (CON, n = 8), an IWT group (n = 12) and an energy expenditure-matched CWT group (n = 12). Training groups were prescribed free-living training, five sessions per week (60 min/session). A three-stage hyperglycaemic clamp, including glucose isotope tracers and skeletal muscle biopsies, was performed before and after a 4 month intervention in a hospitalised setting. No blinding was performed. The improved glycaemic control, which was only seen in the IWT group, was consistent with IWT-induced increases in insulin sensitivity index (49.8 ± 14.6%; p < 0.001), peripheral glucose disposal (14.5 ± 4.9%; p < 0.05) and DI (66.2 ± 21.8%; p < 0.001), with no changes in the CWT or CON group. Moreover, only IWT improved insulin signalling in skeletal muscle via increased insulin-stimulated phosphorylation of AS160 (29.0 ± 10.8%; p < 0.05). No changes were seen in insulin secretion during hyperglycaemia alone, hyperglycaemia + glucagon-like peptide 1 infusion or arginine injection. IWT maintains insulin secretion and improves insulin sensitivity and DI, in contrast to energy expenditure-matched CWT. These results suggest that training with alternating intensity, and not just training volume and mean intensity, is a key determinant of changes in whole body glucose disposal in individuals with type 2 diabetes. ClinicalTrials (NCT01234155).

Oral nutritional supplementation in patients undergoing peritoneal dialysis: a randomised, crossover pilot study.

PubMed

Salamon, Karen M; Lambert, Kelly

2018-06-01

Malnutrition is a significant problem in those undergoing peritoneal dialysis (PD). Factors such as gastrointestinal (GI) symptoms and the need for a fluid reduced diet can limit tolerance and thereby the efficacy of oral nutritional supplements to treat malnutrition. To evaluate the acceptability and impact of two different forms of oral nutrition supplementation for 16 weeks on nutritional markers and quality of life of malnourished patients undergoing PD. A randomised, within-subject cross-over study. Patients assessed as malnourished or with serum albumin <35 g/l were recruited. Participants were randomised to receive either 200 ml of a 1.25 kcal/ml nutrition supplement or a high protein nutrition supplement bar, for eight weeks. Each group then crossed over to receive the alternative supplement for eight weeks. Total intervention time was 16 weeks. Serum albumin, serum transthyretin and food intake were evaluated at baseline, at 8 and 16 weeks. Subjective Global Assessment, the presence of GI symptoms and quality of life were evaluated at baseline and 16 weeks. Sixteen weeks of nutritional support was associated with statistically significant improvements in weight and a reduction in the proportion of patients who were malnourished. There was no difference in the impact of bars compared with liquid oral nutrition supplementation. Patients preferred the fluid supplement to the bars. Sixteen weeks of nutritional support improved nutritional status in malnourished patients on PD. © 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.

PubMed

White, David J; de Klerk, Suzanne; Woods, William; Gondalia, Shakuntla; Noonan, Chris; Scholey, Andrew B

2016-01-19

L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine.

Sinonasal inhalation of dornase alfa administered by vibrating aerosol to cystic fibrosis patients: a double-blind placebo-controlled cross-over trial.

PubMed

Mainz, Jochen G; Schien, Claudia; Schiller, Isabella; Schädlich, Katja; Koitschev, Assen; Koitschev, Christiane; Riethmüller, Joachim; Graepler-Mainka, Uta; Wiedemann, Bärbel; Beck, James F

2014-07-01

Chronic rhinosinusitis significantly impairs CF patients' quality of life and overall health. The Pari-Sinus™ device delivers vibrating aerosol effectively to paranasal sinuses. After a small pilot study to assess sinonasal inhalation of dornase alfa and placebo (isotonic saline) on potential sinonasal outcome measures, we present the subsequent prospective double-blind placebo-controlled crossover-trial. 23 CF patients were randomised to inhale either dornase alfa or isotonic saline for 28 days with the Pari-Sinus™ and after 28 days (wash-out) crossed over to the alternative treatment. The primary outcome parameter was primary nasal symptom score in the disease-specific quality of life Sino-Nasal Outcome-Test-20 (SNOT-20: nasal obstruction/sneezing/runny nose/thick nasal discharge/reduced smelling). Primary nasal symptoms improved significantly with dornase alfa compared with no treatment, while small improvements with isotonic saline did not reach significance. SNOT-20 overall scores improved significantly after dornase alfa compared with isotonic saline (p=0.017). Additionally, sinonasal dornase alfa but not isotonic saline significantly improved pulmonary function (FEF75-25: p=0.021). Vibrating sinonasal inhalation of dornase alfa reduces rhinosinusitis symptoms in CF. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A pilot randomised controlled trial in intensive care patients comparing 7 days' treatment with empirical antibiotics with 2 days' treatment for hospital-acquired infection of unknown origin.

PubMed

Scawn, N; Saul, D; Pathak, D; Matata, B; Kemp, I; Stables, R; Lane, S; Haycox, A; Houten, R

2012-09-01

Management of cardiac intensive care unit (ICU) sepsis is complicated by the high incidence of systemic inflammatory response syndrome, which mimics sepsis but without an infective cause. This pilot randomised trial investigated whether or not, in the ICU, 48 hours of broad-spectrum antibiotic treatment was adequate to safely treat suspected sepsis of unknown and unproven origin and also the predictive power of newer biomarkers of sepsis. The main objective of this pilot study was to provide preliminary data on the likely safety and efficacy of a reduced course of antibiotics for the treatment of ICU infections of unknown origin. A pilot, single-centre, open-label randomised trial. This study was carried out in the ICU of a tertiary heart and chest hospital. Patients being treated within the ICU were recruited into the trial if the intensivist was planning to commence antibiotics because of evidence of systemic inflammatory response syndrome and a strong suspicion of infection but there was no actual known source for that infection. Broad-spectrum antibiotic treatment administered for 48 hours (experimental) compared with treatment for 7 days (control). The primary outcome was a composite outcome of the rate of death or initiation of antibiotic therapy after the completion of the treatment schedule allocated at randomisation. Secondary outcomes included the duration of mechanical ventilation and ICU and hospital stay; the incidence of infection with Clostridium difficile (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008, or methicillin-resistant Staphylococcus aureus (MRSA) (B. S. Weeks & E. Alcamo) Jones & Bartlett International Publishers, 2008; resource utilisation and costs associated with each of the two pilot arms; the ratio of patients screened to patients eligible to patients randomised; the incidence of crossover between groups; and the significance of newer biomarkers for sepsis for predicting patients' need for further antibiotics. A total of 46 patients were recruited into the trial, with 23 randomised to each group. There was no significant difference between the two groups in terms of the composite primary outcome measure. The risk difference was 0.12 [95% confidence interval (CI) 0.11 to 0.13; p = 0.3]. In the 2-day group, four patients (17.4%) required further antibiotics compared with three (13%) in the 7-day group. Four patients died within the trial period and the deaths were not trial related. Patients who died during the trial period received no additional antibiotics in excess of their trial allocation. There were no documented incidences of MRSA or C. difficile infection in either group. No significant differences in adverse events were observed between the groups. Key economic findings were mean antibiotic costs per patient of £168.97 for the 2-day group and £375.86 for the 7-day group. The potential per annum cost saving for the ICU of 2-day treatment was estimated to range from £108,140 to £126,060. Patient screening was considered the biggest barrier to recruitment. There was no crossover between the two randomised groups. Data verification ascertained > 98% accuracy in data collection. Baseline procalcitonin was found to be predictive of the composite outcome (death and needing further antibiotics) (odds ratio 1.79, 95% CI 1.20 to 2.67; p = 0.005). Analysis of baseline procalcitonin also indicated a trend towards it being a predictor of restarting antibiotics, with an odds ratio of 1.45 (95% CI 1.04 to 2.02; p = 0.01). Data from this pilot study suggest that there could be significant benefits of reducing broad-spectrum antibiotic use in the ICU without it undermining patient safety, with a potential cost saving in our unit of over £100,000 per year. Evidence from this pilot trial is not definitive but warrants further investigation using a large randomised controlled trial. Current Controlled Trials ISRCTN82694288. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 36. See the HTA programme website for further project information.

Does a single bout of resistance or aerobic exercise after insulin dose reduction modulate glycaemic control in type 2 diabetes? A randomised cross-over trial.

PubMed

Gordon, Brett A; Bird, Stephen R; MacIsaac, Richard J; Benson, Amanda C

2016-10-01

Regular exercise is advocated for individuals with type 2 diabetes, without fully understanding the acute (0-72h post-exercise) glycaemic response. This study assessed post-exercise glycaemic profiles of non-exercising individuals with insulin treated type 2 diabetes, following resistance and aerobic exercise. Randomised cross-over trial. Fourteen individuals with insulin treated type 2 diabetes (9 males, 5 females) aged 58.1±7.1 years (HbA1c: 8.0±0.6%) were allocated to single sessions of resistance (six whole-body exercises, three sets, 8-10 repetitions, 70% 1RM) and aerobic (30min cycling, 60% VO2peak) exercise, 7-days apart, with the day prior to the first exercise day of each intervention being the control condition. Immediately prior to exercise, insulin dosage was halved and breakfast consumed. Continuous glucose monitoring was undertaken to determine area under the curve and glucose excursions. Blood glucose initially increased (0-2h) following both resistance and aerobic exercise (p<0.001), peaking at 12.3±3.4mmolL(-1) and 12.3±3.3mmolL(-1), respectively. Area under the glucose curve was not statistically different over any of the 24h periods (p=0.12), or different in response to resistance (222±41mmolL(-1)24h(-1)) or aerobic (211±40 mmolL(-1)24h(-1)) exercise (p=0.56). Incidence of hyperglycaemia did not differ between exercise modes (p=0.68). Hypoglycaemic events were identified in three and four participants following resistance and aerobic exercise respectively: these did not require treatment. Glycaemic response is not different between exercise modes, although 50% insulin dose reduction prior to exercise impairs the expected improvement. A common clinical recommendation of 50% insulin dose reduction does not appear to cause adverse glycaemic events. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Botulinum toxin for motor and phonic tics in Tourette's syndrome.

PubMed

Pandey, Sanjay; Srivanitchapoom, Prachaya; Kirubakaran, Richard; Berman, Brian D

2018-01-05

Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging. To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics. We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials. We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration. We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion. Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

Active cycle of breathing technique for cystic fibrosis.

PubMed

Mckoy, Naomi A; Wilson, Lisa M; Saldanha, Ian J; Odelola, Olaide A; Robinson, Karen A

2016-07-05

People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 25 April 2016. Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis.Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis. There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference.

Rehabilitation of divided attention after severe traumatic brain injury: a randomised trial.

PubMed

Couillet, Josette; Soury, Stephane; Lebornec, Gaelle; Asloun, Sybille; Joseph, Pierre-Alain; Mazaux, Jean-Michel; Azouvi, Philippe

2010-06-01

Patients with severe traumatic brain injury (TBI) frequently suffer from a difficulty in dealing with two tasks simultaneously. However, there has been little research on the rehabilitation of divided attention. The objective of the present study was to assess the effectiveness of a rehabilitation programme for divided attention after severe TBI. Twelve patients at a subacute/chronic stage after a severe TBI were included. A randomised AB vs. BA cross-over design was used. Training lasted six weeks, with four one-hour sessions per week. It was compared to a non-specific (control) cognitive training. During experimental treatment, patients were trained to perform two concurrent tasks simultaneously. Each one of the two tasks was first trained as a single task, then both tasks were given simultaneously. A progressive hierarchical order of difficulty was used, by progressively increasing task difficulty following each patient's individual improvement. Patients were randomised in two groups: one starting with dual-task training, the other with control training. Outcome measures included target dual-task measures, executive and working memory tasks, non-target tasks, and the Rating Scale of Attentional Behaviour addressing attentional problems in everyday life. Assessment was not blind to treatment condition. A significant training-related effect was found on dual-task measures and on the divided attention item of the Rating Scale of Attentional Behaviour. There was only little effect on executive measures, and no significant effect on non-target measures. These results suggest that training had specific effects on divided attention and helped patients to deal more rapidly and more accurately with dual-task situations.

Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised study.

PubMed

Riley, John H; Kalberg, Chris J; Donald, Alison; Lipson, David A; Shoaib, Muhammad; Tombs, Lee

2018-01-01

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT). Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV 1 ) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed. UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV 1 (206 mL, 95% CI 167-246), 3-h post-dose FRC (-346 mL, 95% CI -487 to -204) and CAT score (-1.07 units, 95% CI -2.09 to -0.05) versus placebo at week 12. UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status.

A Mediterranean Diet to Improve Cardiovascular and Cognitive Health: Protocol for a Randomised Controlled Intervention Study.

PubMed

Wade, Alexandra T; Davis, Courtney R; Dyer, Kathryn A; Hodgson, Jonathan M; Woodman, Richard J; Keage, Hannah A D; Murphy, Karen J

2017-02-16

The Mediterranean diet has demonstrated efficacy for improving cardiovascular and cognitive health. However, a traditional Mediterranean diet delivers fewer serves of dairy and less dietary calcium than is currently recommended in Australia, which may limit long-term sustainability. The present study aims to evaluate whether a Mediterranean diet with adequate dairy and calcium can improve cardiovascular and cognitive function in an at-risk population, and thereby reduce risk of cardiovascular disease (CVD) and cognitive decline. A randomised, controlled, parallel, crossover design trial will compare a Mediterranean diet supplemented with dairy foods against a low-fat control diet. Forty participants with systolic blood pressure above 120 mmHg and at least two other risk factors of CVD will undertake each dietary intervention for eight weeks, with an eight-week washout period between interventions. Systolic blood pressure will be the primary measure of interest. Secondary outcomes will include measures of cardiometabolic health, dietary compliance, cognitive function, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), psychological well-being and dementia risk. This research will provide empirical evidence as to whether the Mediterranean diet can be modified to provide recommended dairy and calcium intakes while continuing to deliver positive effects for cardiovascular and cognitive health. The findings will hold relevance for the field of preventative healthcare and may contribute to revisions of national dietary guidelines.

A Mediterranean Diet to Improve Cardiovascular and Cognitive Health: Protocol for a Randomised Controlled Intervention Study

PubMed Central

Wade, Alexandra T.; Davis, Courtney R.; Dyer, Kathryn A.; Hodgson, Jonathan M.; Woodman, Richard J.; Keage, Hannah A. D.; Murphy, Karen J.

2017-01-01

The Mediterranean diet has demonstrated efficacy for improving cardiovascular and cognitive health. However, a traditional Mediterranean diet delivers fewer serves of dairy and less dietary calcium than is currently recommended in Australia, which may limit long-term sustainability. The present study aims to evaluate whether a Mediterranean diet with adequate dairy and calcium can improve cardiovascular and cognitive function in an at-risk population, and thereby reduce risk of cardiovascular disease (CVD) and cognitive decline. A randomised, controlled, parallel, crossover design trial will compare a Mediterranean diet supplemented with dairy foods against a low-fat control diet. Forty participants with systolic blood pressure above 120 mmHg and at least two other risk factors of CVD will undertake each dietary intervention for eight weeks, with an eight-week washout period between interventions. Systolic blood pressure will be the primary measure of interest. Secondary outcomes will include measures of cardiometabolic health, dietary compliance, cognitive function, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), psychological well-being and dementia risk. This research will provide empirical evidence as to whether the Mediterranean diet can be modified to provide recommended dairy and calcium intakes while continuing to deliver positive effects for cardiovascular and cognitive health. The findings will hold relevance for the field of preventative healthcare and may contribute to revisions of national dietary guidelines. PMID:28212320

Anthocyanins from fruit juices improve the antioxidant status of healthy young female volunteers without affecting anti-inflammatory parameters: results from the randomised, double-blind, placebo-controlled, cross-over ANTHONIA (ANTHOcyanins in Nutrition Investigation Alliance) study.

PubMed

Kuntz, Sabine; Kunz, Clemens; Herrmann, Johannes; Borsch, Christian H; Abel, Georg; Fröhling, Bettina; Dietrich, Helmut; Rudloff, Silvia

2014-09-28

Anthocyanins (ACN) can exert beneficial health effects not only through their antioxidative potential but also through modulation of inflammatory parameters that play a major role in CVD. A randomised cross-over study was carried out to investigate the effects of ACN-rich beverage ingestion on oxidation- and inflammation-related parameters in thirty healthy female volunteers. The participants consumed 330 ml of beverages (placebo, juice and smoothie with 8·9 (SD 0·3), 983·7 (SD 37) and 840·9 (SD 10) mg/l ACN, respectively) over 14 d. Before and after each intervention, blood and 24 h urine samples were collected. Plasma superoxide dismutase (SOD) and catalase activities increased significantly after ACN-rich beverage ingestion (P<0·001), whereas after placebo juice ingestion no increase could be observed. Plasma glutathione peroxidase and erythrocyte SOD activities were not affected. An increase in Trolox equivalent antioxidant capacity could also be observed after juice (P<0·001) and smoothie (P<0·01) ingestion. The plasma and urinary concentrations of malondialdehyde decreased after ACN-rich beverage ingestion (P<0·001), whereas those of 8-OH-2-deoxyguanosine as well as inflammation-related parameters (IL-2, -6, -8 and -10, C-reactive peptide, soluble cluster of differentiation 40 ligand, TNF-α, monocyte chemoattractant protein-1 and soluble cell adhesion molecules) were not affected. Thus, ingestion of ACN-rich beverages improves antioxidant enzyme activities and plasma antioxidant capacity, thus protecting the body against oxidative stress, a hallmark of ongoing atherosclerosis.

Effectiveness of portable electronic and optical magnifiers for near vision activities in low vision: a randomised crossover trial.

PubMed

Taylor, John J; Bambrick, Rachel; Brand, Andrew; Bray, Nathan; Dutton, Michelle; Harper, Robert A; Hoare, Zoe; Ryan, Barbara; Edwards, Rhiannon T; Waterman, Heather; Dickinson, Christine

2017-07-01

To compare the performance of near vision activities using additional portable electronic vision enhancement systems (p-EVES), to using optical magnifiers alone, by individuals with visual impairment. A total of 100 experienced optical aid users were recruited from low vision clinics at Manchester Royal Eye Hospital, Manchester, UK, to a prospective two-arm cross-over randomised controlled trial. Reading, performance of near vision activities, and device usage were evaluated at baseline; and at the end of each study arm (Intervention A: existing optical aids plus p-EVES; Intervention B: optical aids only) which was after 2 and 4 months. A total of 82 participants completed the study. Overall, maximum reading speed for high contrast sentences was not statistically significantly different for optical aids and p-EVES, although the critical print size and threshold print size which could be accessed with p-EVES were statistically significantly smaller (p < 0.001 in both cases). The optical aids were used for a larger number of tasks (p < 0.001), and used more frequently (p < 0.001). However p-EVES were preferred for leisure reading by 70% of participants, and allowed longer duration of reading (p < 0.001). During the study arm when they had a p-EVES device, participants were able to carry out more tasks independently (p < 0.001), and reported less difficulty with a range of near vision activities (p < 0.001). The study provides evidence that p-EVES devices can play a useful role in supplementing the range of low vision aids used to reduce activity limitation for near vision tasks. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study.

PubMed

Ukhanova, Maria; Wang, Xiaoyu; Baer, David J; Novotny, Janet A; Fredborg, Marlene; Mai, Volker

2014-06-28

The modification of microbiota composition to a 'beneficial' one is a promising approach for improving intestinal as well as overall health. Natural fibres and phytochemicals that reach the proximal colon, such as those present in various nuts, provide substrates for the maintenance of healthy and diverse microbiota. The effects of increased consumption of specific nuts, which are rich in fibre as well as various phytonutrients, on human gut microbiota composition have not been investigated to date. The objective of the present study was to determine the effects of almond and pistachio consumption on human gut microbiota composition. We characterised microbiota in faecal samples collected from volunteers in two separate randomised, controlled, cross-over feeding studies (n 18 for the almond feeding study and n 16 for the pistachio feeding study) with 0, 1·5 or 3 servings/d of the respective nuts for 18 d. Gut microbiota composition was analysed using a 16S rRNA-based approach for bacteria and an internal transcribed spacer region sequencing approach for fungi. The 16S rRNA sequence analysis of 528 028 sequence reads, retained after removing low-quality and short-length reads, revealed various operational taxonomic units that appeared to be affected by nut consumption. The effect of pistachio consumption on gut microbiota composition was much stronger than that of almond consumption and included an increase in the number of potentially beneficial butyrate-producing bacteria. Although the numbers of bifidobacteria were not affected by the consumption of either nut, pistachio consumption appeared to decrease the number of lactic acid bacteria (P< 0·05). Increasing the consumption of almonds or pistachios appears to be an effective means of modifying gut microbiota composition.

Immediate effects after stochastic resonance whole-body vibration on physical performance on frail elderly for skilling-up training: a blind cross-over randomised pilot study.

PubMed

Rogan, Slavko; Schmidtbleicher, Dietmar; Radlinger, Lorenz

2014-10-01

This pilot study examined the feasibility outcome recruitment, safety and compliance of the investigation for stochastic resonance whole-body vibration (SR-WBV) training. Another aim was to evaluate the effect size of one SR-WBV intervention session on Short Physical Performance Battery (SPPB), Expanded Timed Get Up-and-Go (ETGUG), isometric maximal voluntary contraction (IMVC) and rate of force development (IRFD) and chair rising (CR). Randomised double-blinded controlled cross-over pilot study. Feasibility outcomes included recruitment, safety and compliance. For secondary outcomes, SPPB, ETGUG, IMVC, IRFD and CR were measured before and 2-min after intervention. Nonparametric Rank-Order Tests of Puri and Sen L Statistics to Ranked Data were proposed. Wilcoxon signed-ranked tests were used to analyse the differences after SR-WBV intervention and sham intervention. Treatment effects between the interventions were compared by a Mann-Whitney U test. Among 24 eligible frail elderly, 12 agreed to participate and 3 drop out. The adherence was 15 of 24 intervention sessions. For secondary outcome, effect sizes (ES) for SR-WBV intervention on SPPB, ETGUG and CR were determined. This pilot study indicate that the training protocol used in this form for frail elderly individuals is feasible but with modification due to the fact that not all defined feasibility outcomes target was met. SR-WBV with 6 Hz, noise level 4 shows benefit improvements on SPPB (ES 0.52), ETGUG (part sit-to-stand movement: ES 0.81; total time: ES 0.85) and CR (ES 0.66). Further research is desired to determine whether a new adapted training protocol is necessary for SR-WBV in the "skilling up" phase in frail elderly individuals.

Ataluren in cystic fibrosis: development, clinical studies and where are we now?

PubMed

Zainal Abidin, Noreen; Haq, Iram J; Gardner, Aaron I; Brodlie, Malcolm

2017-09-01

Cystic fibrosis (CF) is one of the most common genetically-acquired life-limiting conditions worldwide. The underlying defect is dysfunction of the cystic fibrosis transmembrane-conductance regulator (CFTR) which leads to progressive lung disease and other multi-system effects. Around 10% of people with CF have a class I nonsense mutation that leads to production of shortened CFTR due to a premature termination codon (PTC). Areas covered: We discuss the discovery of the small-molecule drug ataluren, which in vitro has been shown to allow read-through of PTCs and facilitate synthesis of full-length protein. We review clinical studies that have been performed involving ataluren in CF. Early-phase short-term cross-over studies showed improvement in nasal potential difference. A follow-up phase III randomised controlled trial did not show a significant difference for the primary outcome of lung function, however a post-hoc analysis suggested possible benefit in patients not receiving tobramycin. A further randomised controlled trial in patients not receiving tobramycin has been reported as showing no benefit but has not yet been published in full peer-reviewed form. Expert opinion: A small-molecule approach to facilitate read-through of PTCs in nonsense mutations makes intuitive sense. However, at present there is no high-quality evidence of clinical efficacy for ataluren in people with CF.

Effect of alternating postures on cognitive performance for healthy people performing sedentary work.

PubMed

Schwartz, Bernhard; Kapellusch, Jay M; Schrempf, Andreas; Probst, Kathrin; Haller, Michael; Baca, Arnold

2018-06-01

Prolonged sitting is a risk factor for several diseases and the prevalence of worksite-based interventions such as sit-to-stand workstations is increasing. Although their impact on sedentary behaviour has been regularly investigated, the effect of working in alternating body postures on cognitive performance is unclear. To address this uncertainty, 45 students participated in a two-arm, randomised controlled cross-over trial under laboratory conditions. Subjects executed validated cognitive tests (working speed, reaction time, concentration performance) either in sitting or alternating working postures on two separate days (ClinicalTrials.gov Identifier: NCT02863731). MANOVA results showed no significant difference in cognitive performance between trials executed in alternating, standing or sitting postures. Perceived workload did not differ between sitting and alternating days. Repeated measures ANOVA revealed significant learning effects regarding concentration performance and working speed for both days. These results suggest that working posture did not affect cognitive performance in the short term. Practitioner Summary: Prior reports indicated health-related benefits based on alternated (sit/stand) body postures. Nevertheless, their effect on cognitive performance is unknown. This randomised controlled trial showed that working in alternating body postures did not influence reaction time, concentration performance, working speed or workload perception in the short term.

Oral sumatriptan in acute migraine.

PubMed

Goadsby, P J; Zagami, A S; Donnan, G A; Symington, G; Anthony, M; Bladin, P F; Lance, J W

1991-09-28

The efficacy in acute migraine of oral sumatriptan was assessed in a double-blind, randomised, placebo-controlled, crossover study of 61 patients (mean age 39 [SD 10] years). 41 completed treatment of four attacks, two with sumatriptan 100 mg and two with placebo. The response rate (reduction in headache from moderate or severe to mild or absent at 2 h) was 51% (45/89) with sumatriptan and 10% (9/93) with placebo (p less than 0.01); rescue medication was needed at 2 h in 41% and 88%, respectively. Of 28 patients headache-free at 24 h, 11 (39%) had recurrent headache within 24 h. There were no substantial side-effects. Thus, sumatriptan is an effective well-tolerated treatment for acute migraine attacks.

Moderate concentrations of supplemental oxygen worsen hypercapnia in obesity hypoventilation syndrome: a randomised crossover study.

PubMed

Hollier, Carly Ann; Harmer, Alison Rosemary; Maxwell, Lyndal Jane; Menadue, Collette; Willson, Grant Neville; Unger, Gunnar; Flunt, Daniel; Black, Deborah Ann; Piper, Amanda Jane

2014-04-01

In people with obesity hypoventilation syndrome (OHS), breathing 100% oxygen increases carbon dioxide (PCO2), but its effect on pH is unknown. This study investigated the effects of moderate concentrations of supplemental oxygen on PCO2, pH, minute ventilation (VE) and physiological dead space to tidal volume ratio (VD/VT) among people with stable untreated OHS, with comparison to healthy controls. In a double-blind randomised crossover study, participants breathed oxygen concentrations (FiO2) 0.28 and 0.50, each for 20 min, separated by a 45 min washout period. Arterialised-venous PCO2 (PavCO2) and pH, VE and VD/VT were measured at baseline, then every 5 min. Data were analysed using general linear model analysis. 28 participants were recruited (14 OHS, 14 controls). Among OHS participants (mean ± SD arterial PCO2 6.7 ± 0.5 kPa; arterial oxygen 8.9 ± 1.4 kPa) FiO2 0.28 and 0.50 maintained oxygen saturation 98-100%. After 20 min of FiO2 0.28, PavCO2 change (ΔPavCO2) was 0.3 ± 0.2 kPa (p = 0.013), with minimal change in VE and rises in VD/VT of 1 ± 5% (p = 0.012). FiO2 0.50 increased PavCO2 by 0.5 ± 0.4 kPa (p = 0.012), induced acidaemia and increased VD/VT by 3 ± 3% (p = 0.012). VE fell by 1.2 ± 2.1 L/min within 5 min then recovered individually to varying degrees. A negative correlation between ΔVE and ΔPavCO2 (r = -0.60, p = 0.024) suggested that ventilatory responses were the key determinant of PavCO2 rises. Among controls, FiO2 0.28 and 0.50 did not change PavCO2 or pH, but FiO2 0.50 significantly increased VE and VD/VT. Commonly used oxygen concentrations caused hypoventilation, PavCO2 rises and acidaemia among people with stable OHS. This highlights the potential dangers of this common intervention in this group.

Protocol for a placebo-controlled, within-participants crossover trial evaluating the efficacy of intranasal oxytocin to improve pain and function among women with chronic pelvic musculoskeletal pain.

PubMed

Rash, Joshua A; Toivonen, Kirsti; Robert, Magali; Nasr-Esfahani, Maryam; Jarrell, John F; Campbell, Tavis S

2017-04-16

This protocol presents the rationale and design for a trial evaluating the efficacy of intranasal oxytocin in improving pain and function among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide traditionally recognised for involvement in labour, delivery and lactation. Novel evidence suggests that oxytocin decreases pain sensitivity in humans. While oxytocin administration has been reported to lower pain sensitivity among patients experiencing chronic back pain, headache, constipation and colon pain, no research has evaluated the association between intranasal oxytocin and chronic pelvic musculoskeletal pain. The association between oxytocin and pain may differ in women with chronic pelvic musculoskeletal pain relative to other chronic pain conditions because of the abundance of oxytocin receptors in the uterus. This is a prospective, randomised, placebo-controlled, double-blind, within-participants crossover trial. 50 women with chronic pelvic musculoskeletal pain will be recruited through a local chronic pain centre and gynaecology clinics. Women will complete baseline measures and be randomised to an experimental or control condition that involve 2 weeks of self-administering twice-daily doses of 24 IU intranasal oxytocin or placebo, respectively. Women will then undergo a 2-week washout period before crossing over to receive the condition that they had not yet received. The primary outcome will be pain and function measured using the Brief Pain Inventory-Short Form. Secondary outcomes include emotional function, sleep disturbance and global impression of change. This trial will provide data on the 14-day safety and side-effect profile of intranasal oxytocin self-administered as an adjuvant treatment for chronic pelvic musculoskeletal pain. This trial was granted approval from Health Canada and the University of Calgary Conjoint Health Research Ethics Board, and is registered online at ClinicalTrials.gov (#NCT02888574). Results will be disseminated to healthcare professionals through peer-reviewed publications and to the general public through press releases. NCT02888574; 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/.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

PubMed

Peluso, Rosario; Caso, Francesco; Costa, Luisa; Sorbo, Dario; Carraturo, Nello; Di Minno, Matteo Nicola Dario; Carraturo, Federica; Oriente, Alfonso; Balestrieri, Umberto; Minicucci, Annamaria; Del Puente, Antonio; Scarpa, Raffaele

2016-01-01

To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Sea buckthorn decreases and delays insulin response and improves glycaemic profile following a sucrose-containing berry meal: a randomised, controlled, crossover study of Danish sea buckthorn and strawberries in overweight and obese male subjects.

PubMed

Mortensen, Maria Wichmann; Spagner, Camilla; Cuparencu, Cătălina; Astrup, Arne; Raben, Anne; Dragsted, Lars Ove

2017-10-11

Berries and mixed berry products exert acute effects on postprandial glycaemia and insulinemia, but very few berries have been studied, and primarily in normal weight subjects. Sea buckthorn and strawberry are compositionally widely different berries and may likely produce different responses. The effects of strawberry and sea buckthorn on postprandial glycaemia and insulinemia were examined in overweight or obese male subjects. Subjective appetite sensations and ad libitum intake were also examined. The study was conducted as a randomised, controlled, single-blinded, three-way crossover study. Eighteen subjects were studied in three 2-h meal tests followed by a subsequent ad libitum meal. Test meals contained added sucrose and either sea buckthorn, strawberry or no berries with added fructose (control). Blood samples were collected at t = 0, 30, 45, 60, 90 and 120 min. Subjective appetite sensations were recorded at t = 0, 15, 30, 45, 60, 90, 120, and 140 min and subsequent ad libitum intake was recorded. Statistical differences in all continuous measures were evaluated based on the existence of a meal or a time-meal interaction by repeated measures linear model analyses or by differences in AUC by linear mixed models. None of the berries affected postprandial glucose. However, sea buckthorn improved glycaemic profile (44.7%, p < 0.01) compared to control. Sea buckthorn also resulted in a decrease in plasma insulin concentration at 30 min (39.6%, p < 0.01) and at 45 min (16.5%, p < 0.05) compared to control and the maximal increase in plasma insulin was lower following sea buckthorn compared with control (23.6%, p < 0.01). Strawberry did not affect postprandial insulin concentrations compared to control. No differences between control and each of the two berries were observed for any of the appetite parameters, except for desire for something sweet, which was increased following the sea buckthorn meal compared to control. There was no effect on postprandial glucose response to a sugar challenge given together with purees of strawberry or sea buckthorn. Sea buckthorn decreased and delayed the insulin response and improved glycaemic profile compared with control. Strawberry had no such effects. No important differences were seen for the appetite measures. Sea buckthorn might be useful as a culinary tool for lowering meal insulin response.

The effects of continuous positive airway pressure therapy on Troponin-T and N-terminal pro B-type natriuretic peptide in patients with obstructive sleep apnoea: a randomised controlled trial.

PubMed

Chang, Ya-Shu; Yee, Brendon J; Hoyos, Camilla M; Wong, Keith K; Sullivan, David R; Grunstein, Ronald R; Phillips, Craig L

2017-11-01

Untreated obstructive sleep apnoea (OSA) is associated with increased risk of coronary artery disease (CAD) and heart failure. High-sensitivity cardiac troponin (hs Trop-T) and B-type natriuretic peptide (NT-pro-BNP) are sensitive biomarkers for myocardial injury and heart failure respectively. No randomised controlled trials have examined the treatment effect of continuous positive airway pressure (CPAP) in patients with OSA on these biomarkers. Patients >21 years old with apnoea-hypopnoea index (AHI) ≥25/h by overnight polysomnography were recruited. Main exclusion criteria were previous CPAP use and any significant comorbidities including CAD and heart failure. Eligible subjects were randomised to receive CPAP or sham CPAP for eight weeks each in a crossover design with a wash out period of one month between the treatments. Blood samples were collected at 8pm, 3am, and 8am during sleep studies conducted at the end of each eight-week treatment period. Of the 37 patients who were randomised, 28 patients had stored frozen samples available for analysis. In comparison to sham treatment, CPAP significantly lowered the NT-pro-BNP level by 0.91 pmol/L (p = 0.0002). The reduction of 0.235 ng/L in hs Trop-T on CPAP therapy was not statistically significant (p = 0.052). There were no overnight changes, across the three time points, in either biomarker with either treatment. Our study confirms CPAP therapy in patients with moderate-severe OSA reduces NT-pro-BNP, but we did not confirm a significant effect on hs Trop-T. Future larger studies of longer duration incorporating biomarkers and cardiac functional measures are needed to better establish the benefit of OSA treatment. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial.

PubMed

Battelino, T; Conget, I; Olsen, B; Schütz-Fuhrmann, I; Hommel, E; Hoogma, R; Schierloh, U; Sulli, N; Bolinder, J

2012-12-01

The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months. Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.

Foot massage versus quiet presence on agitation and mood in people with dementia: a randomised controlled trial.

PubMed

Moyle, Wendy; Cooke, Marie Louise; Beattie, Elizabeth; Shum, David H K; O'Dwyer, Siobhan T; Barrett, Sue

2014-06-01

There is increasing interest in using complementary and alternative treatments to manage behavioural and psychological symptoms of dementia such as agitation, aggression and depressed mood. To compare the effect of foot massage (intervention) and quiet presence (control) on agitation and mood in people with dementia. A randomised controlled trial using a within-subjects, crossover design. Five long-term care facilities in Brisbane, Australia. The primary outcome was the Cohen-Mansfield Agitation Inventory (CMAI) and the secondary outcome was the Observed Emotion Rating Scale (OERS). The screening and data collection research assistants, families, and care staff were blinded to participant allocation. Participants of the study were 55 long-term care residents aged 74-103 years (mean age 86.5), with moderate to severe dementia and a history of agitated behaviour according to the Pittsburgh Agitation Scale. A computer-program randomised participants to 10-min foot massage (intervention) or quiet presence (control), every weekday for 3 weeks. A carry-over effect was identified in the data, and so the data was treated as a parallel groups RCT. The mean total CMAI increased in both groups (reflecting an increase in agitation) with this increase greater in the quiet presence group than the foot massage group (p=0.03). There was a trend towards a difference on OERS General Alertness, with a positive change in alertness for participants in the foot massage group (indicating reduced alertness) and a negative change for participants in the quiet presence group (indicating increased alertness) (F(1,51)=3.88, p=0.05, partial ή(2)=0.07). The findings highlight the need for further research on the specific conditions under which massage might promote relaxation and improve mood for people with dementia. The unfamiliar research assistants and variations in usual activity may have contributed to the increase in agitation and this needs further research. ACTRN12612000658819. Copyright © 2013 Elsevier Ltd. All rights reserved.

Helping adolescents to better support their peers with a mental health problem: A cluster-randomised crossover trial of teen Mental Health First Aid.

PubMed

Hart, Laura M; Morgan, Amy J; Rossetto, Alyssia; Kelly, Claire M; Mackinnon, Andrew; Jorm, Anthony F

2018-02-01

teen Mental Health First Aid (tMHFA) is a classroom-based training programme for students aged 15-18 years to improve supportive behaviours towards peers, increase mental health literacy and reduce stigma. This research evaluated tMHFA by comparing it to a matched emergency Physical First Aid (PFA) training programme. A cluster-randomised crossover trial matched four public schools in two pairs and then randomised each to first receive tMHFA or PFA for all Year 10 students. In the subsequent calendar year, the new Year 10 cohort received the opposite intervention, giving eight cohorts. Online surveys were administered at baseline and 1 week post-training, measuring quality of first aid intentions, mental health literacy, problem recognition and stigmatising beliefs, towards fictional adolescents with depression and suicidality (John) and social anxiety (Jeanie). A total of 1942 students were randomised (979 received tMHFA, 948 received PFA), 1605 (84%) analysed for the John vignette at baseline and 1116 (69% of baseline) provided post-training data. The primary outcomes, 'helpful first aid intentions' towards John/Jeanie, showed significant group-by-time interactions with medium effect sizes favouring tMHFA ( ds = 0.50-0.58). Compared to PFA, tMHFA students also reported significantly greater improvements in confidence supporting a peer ( ds = 0.22-0.37) and number of adults rated as helpful ( ds = 0.45-0.46) and greater reductions in stigmatising beliefs ( ds = 0.12-0.40) and 'harmful first aid intentions' towards John/Jeanie ( ds = 0.15-0.41). tMHFA is an effective and feasible programme for increasing supportive first aid intentions and mental health literacy in adolescents in the short term. tMHFA could be widely disseminated to positively impact on help seeking for adolescent mental illness.

The acute effects of baobab fruit ( Adansonia digitata) on satiety in healthy adults.

PubMed

Garvey, Rebecca; Clegg, Miriam; Coe, Shelly

2017-06-01

The baobab fruit is high in both dietary fibre and polyphenols and therefore may increase satiety. The aim of the study was to measure the effects of baobab fruit extract on satiety. The study was conducted on 20 healthy participants. The study was a one-day single-blind crossover design. Participants were randomised to either a test smoothie consisting of 15 g of baobab extract or a control smoothie without the addition of baobab. Subjective ratings of satiety were taken on visual analogue scales immediately pre-consumption and then post-consumption, and energy intake at a post ad libitum meal was recorded. Subjective measures of hunger were reduced following the test smoothie compared with the control ( p < 0.05). There was no significant difference in calorie intake at an ad libitum meal. This research has positive implications for the use of baobab for reducing hunger, possibly having a positive effect on weight maintenance.

Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects

PubMed Central

Clifton, Peter M.

2004-01-01

Grape seed extract (GSE) has in vitro antioxidant activity but whether or not it works in vivo is not clear. In a fully randomised, crossover trial with 4-week treatment periods on 36 men and women with above-average vascular risk, we aimed to demonstrate that 2 g/day of GSE (1 g of polyphenols) alone, or with 1 g/day of added quercetin in yoghurt, favourably alters vascular function, endothelial function, and degree of oxidative damage in comparison to a control yoghurt. GSE alone improved flow-mediated dilatation determined ultrasonically by an absolute 1.1% compared with control. There was no effect of the combination of GSE with quercetin. No other blood or urine measure was altered. Thus sufficient polyphenols from GSE appear to be absorbed to influence endothelial nitric oxide production, and GSE has the potential to favourably influence vascular function. PMID:15577189

Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial.

PubMed

Cortes, Jorge E; De Souza, Carmino Antonio; Ayala, Manuel; Lopez, Jose Luis; Bullorsky, Eduardo; Shah, Sandip; Huang, Xiaojun; Babu, K Govind; Abdulkadyrov, Kudrat; de Oliveira, José Salvador Rodrigues; Shen, Zhi-Xiang; Sacha, Tomasz; Bendit, Israel; Liang, Zhizhou; Owugah, Tina; Szczudlo, Tomasz; Khanna, Sadhvi; Fellague-Chebra, Rafik; le Coutre, Philipp D

2016-12-01

Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0-2. Before enrolment, all patients had received 3-18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months' follow-up. This study is registered with ClinicalTrials.gov (NCT00802841). Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95·18% CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 7·9% in favour of nilotinib; 95% CI -6·2 to 22·0, p=0·31). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0·058). Grade 3-4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related. While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included. Novartis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Iron-chelating effect of silymarin in patients with β-thalassemia major: A crossover randomised control trial.

PubMed

Darvishi-Khezri, Hadi; Salehifar, Ebrahim; Kosaryan, Mehrnoush; Karami, Hossein; Mahdavi, Mohammadreza; Alipour, Abbas; Aliasgharian, Aily

2018-03-01

This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with β-thalassemia major. Copyright © 2017 John Wiley & Sons, Ltd.

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

PubMed Central

Jeszka, Jan; Podgórski, Tomasz

2017-01-01

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased (p = 0.049) with a simultaneous reduction of fat mass (p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold (p < 0.0001), threshold load (p = 0.017) and the threshold HR (p < 0.0001), as well as anaerobic peak power (p = 0.005), average power (p = 0.029), maximum speed (p < 0.001) and post-exercise lactate concentrations (p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes. PMID:28708126

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

PubMed

Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

2017-07-14

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased ( p = 0.049) with a simultaneous reduction of fat mass ( p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold ( p < 0.0001), threshold load ( p = 0.017) and the threshold HR ( p < 0.0001), as well as anaerobic peak power ( p = 0.005), average power ( p = 0.029), maximum speed ( p < 0.001) and post-exercise lactate concentrations ( p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes.

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

PubMed Central

Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

2004-01-01

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

Randomised controlled crossover trial of the effect on PtCO2 of oxygen-driven versus air-driven nebulisers in severe chronic obstructive pulmonary disease.

PubMed

Edwards, Llifon; Perrin, Kyle; Williams, Mathew; Weatherall, Mark; Beasley, Richard

2012-11-01

The comparative safety of oxygen versus air-driven nebulised bronchodilators in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain. A randomised controlled trial was performed to assess the effect on the arterial partial pressure of carbon dioxide of nebulised bronchodilator driven with oxygen versus air in stable severe COPD. In an open label randomised study, 18 subjects with stable severe COPD attended on 2 days to receive nebulised bronchodilator therapy driven by air or oxygen. Subjects received 5 mg salbutamol and 0.5 mg ipratropium bromide by nebulisation over 15 min, then, after 5 min, 5 mg salbutamol nebulised over 15 min, followed by 15 min of observation. Transcutaneous carbon dioxide tension (PtCO(2)) and oxygen saturations were recorded at 5 min intervals during the study. The primary outcome was the PtCO(2) after the completion of the second bronchodilator treatment. PtCO(2) was higher with nebulised bronchodilator therapy delivered by oxygen, but decreased back to the level associated with air nebulisation 15 min after completion of the second nebulised dose. One subject experienced an increase in PtCO(2) of 11 mm Hg after the first bronchodilator nebulisation driven by oxygen. The mean PtCO(2) difference between the oxygen and air groups after the second nebulisation was 3.1 mm Hg (95% CI 1.6 to 4.5, p<0.001). Nebulisers driven with oxygen result in significantly higher levels of PtCO(2) than those driven with air in patients with severe COPD. The study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12610000080022).

Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

PubMed

Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Latshang, Tsogyal D; Lo Cascio, Christian M; Sadler, Ross; Stadelmann, Katrin; Tesler, Noemi; Huber, Reto; Achermann, Peter; Bloch, Konrad E; Kohler, Malcolm

2014-05-01

Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/μl 95 % CI -370.8/-119.0, lactadherin+ -202/μl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/μl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 μl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised study

PubMed Central

Kalberg, Chris J.; Donald, Alison; Lipson, David A.; Shoaib, Muhammad; Tombs, Lee

2018-01-01

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT). Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed. UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV1 (206 mL, 95% CI 167–246), 3-h post-dose FRC (−346 mL, 95% CI −487 to −204) and CAT score (−1.07 units, 95% CI −2.09 to −0.05) versus placebo at week 12. UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status. PMID:29322050

Dietary grape powder increases IL-1ß and IL-6 production by lipopolysaccharide-activated monocytes and reduces plasma concentrations of large LDL-cholesterol particles in obese humans

USDA-ARS?s Scientific Manuscript database

Obesity increases the risk of developing cardiovascular disease, hypertension, type 2 diabetes, and bacterial and viral infections when compared to the normal weight population. In a 9 wk randomised, double-blind crossover study, 24 obese subjects between 20-60 y old and with a BMI between 30-45 k...

Dietary nitrate lowers ambulatory blood pressure in treated, uncontrolled hypertension: a 7-d, double-blind, randomised, placebo-controlled, cross-over trial.

PubMed

Kerley, Conor P; Dolan, Eamon; James, Philip E; Cormican, Liam

2018-03-01

Dietary nitrate has been shown to increase nitrate/nitrite levels and decrease blood pressure (BP) in multiple populations. There are few reports among hypertensives and these reports have provided conflicting evidence. We aimed to assess the effect of daily nitrate compared with placebo in subjects with uncontrolled hypertension (HTN). On day 0, hypertensives wore an ambulatory BP monitor (ABPM) for 24 h and blood was taken. Subjects were then randomised to 7-d nitrate-rich beetroot juice (NO3 -) (12·9 mmol nitrate) followed by 7-d nitrate-depleted beetroot juice (0·5 mmol nitrate) or vice versa. ABPM and blood were assessed before and after both conditions. In all, twenty subjects with treated yet uncontrolled HTN entered and completed the trial (mean age=62·5 years, mean BMI=30·7 kg/m2). Baseline BP was 137/80 (sd 7/7) mmHg. Dietary nitrate was well tolerated and resulted in significantly increased plasma nitrite (P=0·0004) and decreased 24-h systolic BP and diastolic BP compared with placebo (-8 mmHg; P=0·012 and -4 mmHg; P=0·018, respectively). Our results support the existing data suggesting an anti-hypertensive effect of dietary nitrate in treated yet uncontrolled hypertensives. Targeted dietary strategies appear promising contributors to BP control.

Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study.

PubMed

Bally, Lia; Thabit, Hood; Kojzar, Harald; Mader, Julia K; Qerimi-Hyseni, Jehona; Hartnell, Sara; Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Pieber, Thomas R; Evans, Mark L; Hovorka, Roman

2017-04-01

Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA 1c below 7·5% (58 mmol/mol). In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA 1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% [SD 8·1] when participants used usual pump therapy vs 76·2% [6·4] when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53-74, p<0·0001) and below 2·8 mmol/L by 76% (59-86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred. Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA 1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted. Swiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z). 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 effects of specialist and on-call respiratory physiotherapy treatments in mechanically ventilated children: A randomised crossover trial.

PubMed

Shannon, Harriet; Stocks, Janet; Gregson, Rachael K; Dunne, Catherine; Peters, Mark J; Main, Eleanor

2015-12-01

The study investigated treatment outcomes when respiratory physiotherapy was delivered by non-respiratory on-call physiotherapists, compared with specialist respiratory physiotherapists. Prospective, randomised crossover trial. Paediatric, tertiary care hospital in the United Kingdom. Mechanically ventilated children requiring two physiotherapy interventions during a single day were eligible. Twenty two physiotherapists (10 non-respiratory) and 93 patients were recruited. Patients received one treatment from a non-respiratory physiotherapist and another from a respiratory physiotherapist, in a randomised order. Treatments were individualised to the patients' needs, often including re-positioning followed by manual lung inflations, chest wall vibrations and endotracheal suction. The primary outcome was respiratory compliance. Secondary outcomes included adverse physiological events and clinically important respiratory changes (according to an a priori definition). Treatments delivered to 63 patients were analysed. There were significant improvements to respiratory compliance (mean increase [95% confidence intervals], 0.07 and 0.08ml·cmH2O(-1)·kg(-1) [0.01 to 0.14 and 0.04 to 0.13], p<0.01, for on-call and respiratory physiotherapists' treatments respectively). Case-by-case, there were fewer clinically important improvements following non-respiratory physiotherapists' treatments compared with the respiratory physiotherapists' (n=27 [43%] versus n=40 [63%], p=0.03). Eleven adverse events occurred, eight following non-respiratory physiotherapists' treatments. Significant disparities exist in treatment outcomes when patients are treated by non-respiratory on-call physiotherapists, compared with specialist respiratory physiotherapists. There is an urgent need for targeted training strategies, or alternative service delivery models, to be explored. This should aim to address the quality of respiratory physiotherapy services, both during and outside of normal working hours. Clinicaltrials.gov, NCT01999426. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Choosing appropriate analysis methods for cluster randomised cross-over trials with a binary outcome.

PubMed

Morgan, Katy E; Forbes, Andrew B; Keogh, Ruth H; Jairath, Vipul; Kahan, Brennan C

2017-01-30

In cluster randomised cross-over (CRXO) trials, clusters receive multiple treatments in a randomised sequence over time. In such trials, there is usual correlation between patients in the same cluster. In addition, within a cluster, patients in the same period may be more similar to each other than to patients in other periods. We demonstrate that it is necessary to account for these correlations in the analysis to obtain correct Type I error rates. We then use simulation to compare different methods of analysing a binary outcome from a two-period CRXO design. Our simulations demonstrated that hierarchical models without random effects for period-within-cluster, which do not account for any extra within-period correlation, performed poorly with greatly inflated Type I errors in many scenarios. In scenarios where extra within-period correlation was present, a hierarchical model with random effects for cluster and period-within-cluster only had correct Type I errors when there were large numbers of clusters; with small numbers of clusters, the error rate was inflated. We also found that generalised estimating equations did not give correct error rates in any scenarios considered. An unweighted cluster-level summary regression performed best overall, maintaining an error rate close to 5% for all scenarios, although it lost power when extra within-period correlation was present, especially for small numbers of clusters. Results from our simulation study show that it is important to model both levels of clustering in CRXO trials, and that any extra within-period correlation should be accounted for. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Calcium phosphate supplementation increases faecal Lactobacillus spp. in a randomised trial of young adults.

PubMed

Dahl, W J; Ford, A L; Coppola, J A; Lopez, D; Combs, W; Rohani, A; Ukhanova, M; Culpepper, T; Tompkins, T A; Christman, M; Mai, V

2016-02-01

The aim of the studies was to determine the effects of calcium carbonate and calcium phosphate supplementation on faecal Lactobacillus spp., with and without a probiotic supplement, in healthy adults. Study 1 comprised of a randomised, double-blind, crossover design; participants (n=15) received 2 capsules/d of 250 mg elemental calcium as calcium carbonate (Ca1) and calcium phosphate (Ca2) each for 2-week periods, with 2-week baseline and washout periods. Study 2 was a randomised, double-blind, crossover design; participants (n=17) received 2 capsules/d of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 (probiotic) alone, the probiotic with 2 capsules/d of Ca1, and probiotic with 2 capsules/d of Ca2 each for 2-week periods with 2-week baseline and washout periods. In both studies, stools were collected during the baseline, intervention and washout periods for Lactobacillus spp. quantification and qPCR analyses. Participants completed daily questionnaires of stool frequency and compliance. In Study 1, neither calcium supplement influenced viable counts of resident Lactobacillus spp., genome equivalents of lactic acid bacteria or stool frequency. In Study 2, faecal Lactobacillus spp. counts were significantly enhanced from baseline when the probiotic was administered with Ca2 (4.83±0.30, 5.79±0.31) (P=0.02), but not with Ca1 (4.98±0.31) or with the probiotic alone (5.36±0.31, 5.55±0.29) (not significant). Detection of L. helveticus R0052 and L. rhamnosus R0011 was significantly increased with all treatments, but did not differ among treatments. There were no changes in weekly stool frequency. Calcium phosphate co-administration may increase gastrointestinal survival of orally-administered Lactobacillus spp.

A crossover randomised and controlled trial of the impact of active video games on motor coordination and perceptions of physical ability in children at risk of Developmental Coordination Disorder.

PubMed

Straker, L; Howie, E; Smith, A; Jensen, L; Piek, J; Campbell, A

2015-08-01

Impaired motor development can significantly affect a child's life and may result in an increased risk of a range of physical and psychological disorders. Active video game (AVG) interventions have been demonstrated to enhance motor skills in children with Developmental Coordination Disorder (DCD); however a home-based intervention has not been assessed. The primary aim of this study was to compare the changes in motor coordination between a 16 week period of AVG use, with 16 weeks of normal activities (NAG). The secondary aim was to compare the child and parent perceptions of their physical performance between the AVG and NAG conditions. Twenty-one 9-12 year olds (10 males) were confirmed to be at risk of DCD (⩽ 16th percentile Movement Assessment Battery for Children-2nd edition (MABC-2) and ⩽ 15th percentile Developmental Coordination Disorder Questionnaire (DCDQ)) and participated in this crossover randomised and controlled trial. Data was collected at study entry, after the first 16 week condition and following the final 16 week condition, including; (1) the MABC-2, (2) three-dimensional motion analysis of single leg balance and finger-nose tasks, and (3) parent perception of physical skills. Participant perception of physical skills was collected only after the first and second conditions. There was no significant difference between AVG and NAG for any of the primary variables including the MABC-2, balance centre-of-mass path distance and finger-nose path distance. There was no significant intervention effect for secondary measures of motor coordination; however the children perceived their motor skills to be significantly enhanced as a result of the AVG intervention in comparison to the period of no intervention. A 16 week home based AVG intervention did not enhance motor skills in children with DCD, although they perceived their physical skills to be significantly improved. Australia and New Zealand Clinical trials Registry (ACTRN 12611000400965). Copyright © 2015 Elsevier B.V. All rights reserved.

Renal and Cardiovascular Effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial

PubMed Central

Mordi, Natalie A; Mordi, Ify R; Singh, Jagdeep S; Baig, Fatima; Choy, Anna-Maria; McCrimmon, Rory J; Struthers, Allan D; Lang, Chim C

2017-01-01

Introduction Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium–glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters. The effects of SGLT2 inhibitors as an osmotic diuretic and on natriuresis may underlie the cardiovascular and renal benefits demonstrated in the recent EMPA-REG study. Methods and analysis To assess the effect of SGLT2 inhibitors when used in combination with a loop diuretic, the RECEDE-CHF (Renal and Cardiovascular Effects of SGLT2 inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure) trial is a single-centre, randomised, double-blind, placebo-controlled, cross-over trial conducted in a secondary care setting within NHS Tayside, Scotland. 34 eligible participants, aged between 18 and 80 years, with stable T2D and CHF will be recruited. Renal physiological testing will be performed at two points (week 1 and week 6) on each arm to assess the effect of 25 mg empagliflozin, on the primary and secondary outcomes. Participants will be enrolled in the trial for a total period between 14 and 16 weeks. The primary outcome will assess the effect of empagliflozin versus placebo on urine output. The secondary outcomes are to assess the effect of empagliflozin on glomerular filtration rate, cystatin C, urinary sodium excretion, urinary protein/creatinine ratio and urinary albumin/creatinine ratio when compared with placebo. Ethics and dissemination Ethics approval was obtained by the East of Scotland Research Ethics Service. Results of the trial will be submitted for publication in a peer-reviewed journal. Trial registration number NCT03226457; Pre-results. PMID:29042392

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.

Effect of supplementation of fermented milk drink containing probiotic Lactobacillus casei Shirota on the concentrations of aflatoxin biomarkers among employees of Universiti Putra Malaysia: a randomised, double-blind, cross-over, placebo-controlled study.

PubMed

Mohd Redzwan, Sabran; Abd Mutalib, Mohd Sokhini; Wang, Jia-Sheng; Ahmad, Zuraini; Kang, Min-Su; Abdul Rahman, Nurul 'Aqilah; Nikbakht Nasrabadi, Elham; Jamaluddin, Rosita

2016-01-14

Human exposure to aflatoxin is through the diet, and probiotics are able to bind aflatoxin and prevent its absorption in the small intestine. This study aimed to determine the effectiveness of a fermented milk drink containing Lactobacillus casei Shirota (LcS) (probiotic drink) to prevent aflatoxin absorption and reduce serum aflatoxin B1-lysine adduct (AFB1-lys) and urinary aflatoxin M1 concentrations. The present study was a randomised, double-blind, cross-over, placebo-controlled study with two 4-week intervention phases. In all, seventy-one subjects recruited from the screening stage were divided into two groups--the Yellow group and the Blue group. In the 1st phase, one group received probiotic drinks twice a day and the other group received placebo drinks. Blood and urine samples were collected at baseline, 2nd and 4th week of the intervention. After a 2-week wash-out period, the treatments were switched between the groups, and blood and urine samples were collected at the 6th, 8th and 10th week (2nd phase) of the intervention. No significant differences in aflatoxin biomarker concentrations were observed during the intervention. A within-group analysis was further carried out. Aflatoxin biomarker concentrations were not significantly different in the Yellow group. Nevertheless, ANOVA for repeated measurements indicated that AFB1-lys concentrations were significantly different (P=0·035) with the probiotic intervention in the Blue group. The 2nd week AFB1-lys concentrations (5·14 (SD 2·15) pg/mg albumin (ALB)) were significantly reduced (P=0·048) compared with the baseline (6·24 (SD 3·42) pg/mg ALB). Besides, the 4th week AFB1-lys concentrations were significantly lower (P<0·05) with probiotic supplementation than with the placebo. Based on these findings, a longer intervention study is warranted to investigate the effects of continuous LcS consumption to prevent dietary aflatoxin exposure.

Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock.

PubMed

Unverzagt, Susanne; Buerke, Michael; de Waha, Antoinette; Haerting, Johannes; Pietzner, Diana; Seyfarth, Melchior; Thiele, Holger; Werdan, Karl; Zeymer, Uwe; Prondzinsky, Roland

2015-03-27

Intra-aortic balloon pump counterpulsation (IABP) is currently the most commonly used mechanical assist device for patients with cardiogenic shock due to acute myocardial infarction. Although there has been only limited evidence from randomised controlled trials, the previous guidelines of the American Heart Association/American College of Cardiology (AHA/ACC) and the European Society of Cardiology (ESC) strongly recommended the use of the IABP in patients with infarction-related cardiogenic shock on the basis of pathophysiological considerations, non-randomised trials and registry data. The recent guidelines downgraded the recommendation based on a meta-analysis which could only include non-randomised trials showing conflicting results. Up to now, there have been no guideline recommendations and no actual meta-analysis including the results of the large randomised multicentre IABP-SHOCK II Trial which showed no survival benefit with IABP support. This systematic review is an update of the review published in 2011. To evaluate, in terms of efficacy and safety, the effect of IABP versus non-IABP or other assist devices guideline compliant standard therapy on mortality and morbidity in patients with acute myocardial infarction complicated by cardiogenic shock. Searches of CENTRAL, MEDLINE (Ovid) and EMBASE (Ovid), LILACS, IndMed and KoreaMed, registers of ongoing trials and proceedings of conferences were updated in October 2013. Reference lists were scanned and experts in the field contacted to obtain further information. No language restrictions were applied. Randomised controlled trials on patients with acute myocardial infarction complicated by cardiogenic shock. Data collection and analysis were performed according to the published protocol. Individual patient data were provided for six trials and merged with aggregate data. Summary statistics for the primary endpoints were hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Seven eligible studies were identified from a total of 2314 references. One new study with 600 patients was added to the original review. Four trials compared IABP to standard treatment and three to other percutaneous left assist devices (LVAD). Data from a total of 790 patients with acute myocardial infarction and cardiogenic shock were included in the updated meta-analysis: 406 patients were treated with IABP and 384 patients served as controls; 339 patients were treated without assisting devices and 45 patients with other LVAD. The HR for all-cause 30-day mortality of 0.95 (95% CI 0.76 to 1.19) provided no evidence for a survival benefit. Different non-fatal cardiovascular events were reported in five trials. During hospitalisation, 11 and 4 out of 364 patients from the intervention groups suffered from reinfarction or stroke, respectively. Altogether 5 out of 363 patients from the control group suffered from reinfarction or stroke. Reocclusion was treated with subsequent re-revascularization in 6 out of 352 patients from the intervention group and 13 out of 353 patients of the control group. The high incidence of complications such as moderate and severe bleeding or infection in the control groups has to be attributed to interventions with other LVAD. Possible reasons for bias were more frequent in small studies with high cross-over rates, early stopping and the inclusion of patients with IABP at randomisation. Available evidence suggests that IABP may have a beneficial effect on some haemodynamic parameters. However, this did not result in survival benefits so there is no convincing randomised data to support the use of IABP in infarct-related cardiogenic shock.

Planned early delivery versus expectant management for monoamniotic twins.

PubMed

Shub, Alexis; Walker, Susan P

2015-04-23

Monoamniotic twin pregnancies are formed when a single egg is fertilised and the resulting inner cell mass splits to form twins sharing the same amniotic sac. This condition is rare and affects about one in 10,000 pregnancies overall. Monoamniotic twin pregnancies are susceptible to complications including cord entanglement, increased congenital anomalies, intrauterine growth restriction, twin-to-twin transfusion syndrome and increased perinatal mortality. All twin pregnancies also carry additional maternal risks including pre-eclampsia, anaemia, antepartum haemorrhage, postpartum haemorrhage and operative delivery.The optimal timing for the delivery of monoamniotic twins is not known. The options include 'planned early delivery' between 32 and 34 weeks, or alternatively awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks' gestation), unless there is a specific indication for earlier delivery. To assess whether routine early delivery in monoamniotic twin pregnancies improves fetal, neonatal or maternal outcomes compared with 'expectant management'. Expectant management means awaiting spontaneous labour at least up until the usual time of planned delivery for other monochorionic twins (approximately 36 to 38 weeks' gestation in many centres), unless a specific indication for delivery occurs in the meantime, e.g. for non-reassuring antenatal testing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015). Published and unpublished randomised controlled trials (including cluster-randomised trials) comparing outcomes for women and infants who were randomised to planned early delivery of a monoamniotic twin pregnancy with outcomes for women and infants who were randomised to either planned term delivery or expectant management. However, we did not identify any trials for inclusion in this review.Quasi-randomised controlled trials, trials published in abstract form only, and trials using a cross-over design are not eligible for inclusion in this review. No trials were identified by the search strategy. No trials were identified by the search strategy. Monoamniotic twins are rare, and there is insufficient randomised controlled evidence on which to draw strong conclusions about the best management. In their absence, we can refer to historical case series and expert consensus. Management plans should take into consideration the availability of high-quality neonatal care if early delivery is chosen. Women and their families should be involved in the decision making about these high-risk pregnancies.Ongoing, multicentre audits of maternal and perinatal outcomes for monoamniotic twins are needed in order to inform families and clinicians about up-to-date perinatal outcomes with contemporary obstetric practice. Research should consider the social and economic implications of planned interventions, as well as the perinatal outcomes.

The Effect of Beta Adrenergic Blockade on Ratings of Perceived Exertion.

DTIC Science & Technology

1984-01-01

exrcis is uvo Hughson, et al. (47) investigated the effect of beta blockade using a single, 100-mg oral dose of metoprolol or matched placebo on 12...administered either placebo, propranolol (80 mug) or metoprolol (100 mug) in a double- blind, randomised manner. Before the muscle-strength tests were...The non-selective BABA propranolol and the selective agent metoprolol were compared with a placebo in a double blind cross-over design. Measurements

Rationale and methods of a randomised cross-over cluster trial to assess the effectiveness of MOVI-KIDS on preventing obesity in pre-schoolers.

PubMed

Martínez-Vizcaino, Vicente; Mota, Jorge; Solera-Martínez, Montserrat; Notario-Pacheco, Blanca; Arias-Palencia, Natalia; García-Prieto, Jorge Cañete; González-García, Alberto; Álvarez-Bueno, Celia; Sánchez-López, Mairena

2015-02-22

Childhood obesity has become an alarming worldwide increasing public health problem. The earlier adiposity rebound occurs, the greater the risk of becoming obese during puberty and adolescence. It has been speculated about the potential influence of vigorous physical activity on modifying the age of onset of adiposity rebound. Moreover, studies aimed to evaluate the effectiveness of physical activity interventions programs on reducing adiposity and other cardiovascular risk factors in children younger than 6 years are scarce. This paper describes the rationale and methods of a study aimed to test the effectiveness of a two-years multidimensional pre-school intervention on preventing obesity and improving physical fitness during the adiposity rebound period. Twenty-one schools from the provinces of Cuenca and Ciudad Real, Spain, were randomised to an intervention and a control arm. In the first academic year, children in third grade of pre-school and first grade of primary school in the intervention group received the physical activity intervention (MOVI-KIDS). After an academic year schools were crossed over to the alternative arm. According to the socio-ecological model, the intervention included children, their parents and teachers, and the school environment where MOVI-KIDS was conducted. MOVI-KIDS consisted of: i) three-h/week sessions of recreational non-competitive physical activity in after-school time; ii) educational materials to parents and teachers about physical activity benefits and sedentary lifestyle risks; and iii) modifications in the playground to promote physical activity during recess. Baseline and post-intervention outcomes are going to be measured in both arms three times, at the beginning and at the end of first academic year, and at the end of the second academic year. Primary outcomes included body mass index, waist circumference, triceps skinfold thickness, percentage of both body fat and fat-free mass, and blood pressure. Secondary end points were physical activity, fitness, and carotid intima-media thickness. This paper reports the design of a randomised cross-over cluster trial aimed at assessing the effectiveness of the multidimensional physical activity intervention (MOVI-KIDS) during two years in pre-school children. Clinical trials.gov: NCT01971840 . (Date of registration: Initial Release: 10/07/2013; Record Verification: 23/10/2013).

10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension.

PubMed

Bone, Henry G; Wagman, Rachel B; Brandi, Maria L; Brown, Jacques P; Chapurlat, Roland; Cummings, Steven R; Czerwiński, Edward; Fahrleitner-Pammer, Astrid; Kendler, David L; Lippuner, Kurt; Reginster, Jean-Yves; Roux, Christian; Malouf, Jorge; Bradley, Michelle N; Daizadeh, Nadia S; Wang, Andrea; Dakin, Paula; Pannacciulli, Nicola; Dempster, David W; Papapoulos, Socrates

2017-07-01

Long-term safety and efficacy of osteoporosis treatment are important because of the chronic nature of the disease. We aimed to assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of postmenopausal women with osteoporosis. In the multicentre, randomised, double-blind, placebo-controlled, phase 3 FREEDOM trial, postmenopausal women aged 60-90 years with osteoporosis were enrolled in 214 centres in North America, Europe, Latin America, and Australasia and were randomly assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years. All participants who completed the FREEDOM trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the open-label, 7-year extension, in which all participants received denosumab. The data represent up to 10 years of denosumab exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (long-term group), and up to 7 years for women who received 3 years of placebo and transitioned to denosumab in the extension (crossover group). The primary outcome was safety monitoring, comprising assessments of adverse event incidence and serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry and haematology), and participant incidence of denosumab antibody formation. Secondary outcomes included new vertebral, hip, and non-vertebral fractures as well as bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius. Analyses were done according to the randomised FREEDOM treatment assignments. All participants who received at least one dose of investigational product in FREEDOM or the extension were included in the combined safety analyses. All participants who enrolled in the extension with observed data were included in the efficacy analyses. The FREEDOM trial (NCT00089791) and its extension (NCT00523341) are both registered with ClinicalTrials.gov. Between Aug 3, 2004, and June 1, 2005, 7808 women were enrolled in the FREEDOM study. 5928 (76%) women were eligible for enrolment in the extension, and of these, 4550 (77%) were enrolled (2343 long-term, 2207 crossover) between Aug 7, 2007, and June 20, 2008. 2626 women (1343 long-term; 1283 crossover) completed the extension. The yearly exposure-adjusted participant incidence of adverse events for all individuals receiving denosumab decreased from 165·3 to 95·9 per 100 participant-years over the course of 10 years. Serious adverse event rates were generally stable over time, varying between 11·5 and 14·4 per 100 participant-years. One atypical femoral fracture occurred in each group during the extension. Seven cases of osteonecrosis of the jaw were reported in the long-term group and six cases in the crossover group. The yearly incidence of new vertebral fractures (ranging from 0·90% to 1·86%) and non-vertebral fractures (ranging from 0·84% to 2·55%) remained low during the extension, similar to rates observed in the denosumab group during the first three years of the FREEDOM study, and lower than rates projected for a virtual long-term placebo cohort. In the long-term group, BMD increased from FREEDOM baseline by 21·7% at the lumbar spine, 9·2% at total hip, 9·0% at femoral neck, and 2·7% at the one-third radius. In the crossover group, BMD increased from extension baseline by 16·5% at the lumbar spine, 7·4% at total hip, 7·1% at femoral neck, and 2·3% at one-third radius. Denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau. Amgen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sample size calculation for stepped wedge and other longitudinal cluster randomised trials.

PubMed

Hooper, Richard; Teerenstra, Steven; de Hoop, Esther; Eldridge, Sandra

2016-11-20

The sample size required for a cluster randomised trial is inflated compared with an individually randomised trial because outcomes of participants from the same cluster are correlated. Sample size calculations for longitudinal cluster randomised trials (including stepped wedge trials) need to take account of at least two levels of clustering: the clusters themselves and times within clusters. We derive formulae for sample size for repeated cross-section and closed cohort cluster randomised trials with normally distributed outcome measures, under a multilevel model allowing for variation between clusters and between times within clusters. Our formulae agree with those previously described for special cases such as crossover and analysis of covariance designs, although simulation suggests that the formulae could underestimate required sample size when the number of clusters is small. Whether using a formula or simulation, a sample size calculation requires estimates of nuisance parameters, which in our model include the intracluster correlation, cluster autocorrelation, and individual autocorrelation. A cluster autocorrelation less than 1 reflects a situation where individuals sampled from the same cluster at different times have less correlated outcomes than individuals sampled from the same cluster at the same time. Nuisance parameters could be estimated from time series obtained in similarly clustered settings with the same outcome measure, using analysis of variance to estimate variance components. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial.

PubMed

Richter, Chesney K; Skulas-Ray, Ann C; Fleming, Jennifer A; Link, Christina J; Mukherjea, Ratna; Krul, Elaine S; Kris-Etherton, Penny M

2017-05-01

Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (-2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.

Lubiprostone decreases the small bowel transit time by capsule endoscopy: an exploratory, randomised, double-blind, placebo-controlled 3-way crossover study.

PubMed

Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

2014-01-01

The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE.

Instructional methods and cognitive and learning styles in web-based learning: report of two randomised trials.

PubMed

Cook, David A; Gelula, Mark H; Dupras, Denise M; Schwartz, Alan

2007-09-01

Adapting web-based (WB) instruction to learners' individual differences may enhance learning. Objectives This study aimed to investigate aptitude-treatment interactions between learning and cognitive styles and WB instructional methods. We carried out a factorial, randomised, controlled, crossover, post-test-only trial involving 89 internal medicine residents, family practice residents and medical students at 2 US medical schools. Parallel versions of a WB course in complementary medicine used either active or reflective questions and different end-of-module review activities ('create and study a summary table' or 'study an instructor-created table'). Participants were matched or mismatched to question type based on active or reflective learning style. Participants used each review activity for 1 course module (crossover design). Outcome measurements included the Index of Learning Styles, the Cognitive Styles Analysis test, knowledge post-test, course rating and preference. Post-test scores were similar for matched (mean +/- standard error of the mean 77.4 +/- 1.7) and mismatched (76.9 +/- 1.7) learners (95% confidence interval [CI] for difference - 4.3 to 5.2l, P = 0.84), as were course ratings (P = 0.16). Post-test scores did not differ between active-type questions (77.1 +/- 2.1) and reflective-type questions (77.2 +/- 1.4; P = 0.97). Post-test scores correlated with course ratings (r = 0.45). There was no difference in post-test subscores for modules completed using the 'construct table' format (78.1 +/- 1.4) or the 'table provided' format (76.1 +/- 1.4; CI - 1.1 to 5.0, P = 0.21), and wholist and analytic styles had no interaction (P = 0.75) or main effect (P = 0.18). There was no association between activity preference and wholist or analytic scores (P = 0.37). Cognitive and learning styles had no apparent influence on learning outcomes. There were no differences in outcome between these instructional methods.

Effects of whole-grain rye porridge with added inulin and wheat gluten on appetite, gut fermentation and postprandial glucose metabolism: a randomised, cross-over, breakfast study.

PubMed

Lee, Isabella; Shi, Lin; Webb, Dominic-Luc; Hellström, Per M; Risérus, Ulf; Landberg, Rikard

2016-12-01

Whole-grain rye foods reduce appetite, insulin and sometimes glucose responses. Increased gut fermentation and plant protein may mediate the effect. The aims of the present study were to investigate whether the appetite-suppressing effects of whole-grain rye porridge could be enhanced by replacing part of the rye with fermented dietary fibre and plant protein, and to explore the role of gut fermentation on appetite and metabolic responses over 8 h. We conducted a randomised, cross-over study using two rye porridges (40 and 55 g), three 40-g rye porridges with addition of inulin:gluten (9:3; 6:6; 3:9 g) and a refined wheat bread control (55 g), served as part of complete breakfasts. A standardised lunch and an ad libitum dinner were served 4 and 8 h later, respectively. Appetite, breath hydrogen and methane, glucose, insulin and glucagon-like peptide-1 (GLP-1) responses were measured over 8 h. Twenty-one healthy men and women, aged 23-60 years, with BMI of 21-33 kg/m2 participated in this study. Before lunch, the 55-g rye porridges lowered hunger by 20 % and desire to eat by 22 % and increased fullness by 29 % compared with wheat bread (P<0·05). Breath hydrogen increased proportionally to dietary fibre content (P<0·05). Plasma glucose after lunch was 6 % lower after the 55-g rye porridges compared with wheat bread (P<0·05) and correlated to breath hydrogen (P<0·001). No differences were observed in ad libitum food intake, insulin or GLP-1. We conclude that no further increase in satiety was observed when replacing part of the rye with inulin and gluten compared with plain rye porridges.

Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.

PubMed

Cambau, Emmanuelle; Durand-Zaleski, Isabelle; Bretagne, Stéphane; Brun-Buisson, Christian; Cordonnier, Catherine; Duval, Xavier; Herwegh, Stéphanie; Pottecher, Julien; Courcol, René; Bastuji-Garin, Sylvie

2017-11-01

Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE). Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler ® SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE). A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4-20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98-39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP €14,826, €18,118 ± 17,775; CP €17,828, €18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients. Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

A mixed diet supplemented with L-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects.

PubMed

Halschou-Jensen, Kia; Bach Knudsen, Knud E; Nielsen, Søren; Bukhave, Klaus; Andersen, Jens R

2015-01-14

In addition to a yet-to-be published study showing arabinose to have an inhibiting effect on maltase, in vitro studies have shown L-arabinose to exert an inhibiting effect on small-intestinal sucrase and maltase and the consumption of a sucrose-rich drink containing L-arabinose to exert positive effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding L-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of L-arabinose added to a sugar drink could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose and starch from wheat flour (meal A) or starch from wheat flour (meal B) supplemented with 0, 5 and 10 % L-arabinose by weight after a 12 h fast. A total of six healthy men participated in study 2, a randomised, double-blind, cross-over trial. In this study, the subjects also consumed meal B served in two different textures and a liquid meal with maltose supplemented with 0 and 20% L-arabinose. In addition, 1·5 g of paracetamol was chosen as an indirect marker to assess gastric emptying. Postprandial plasma glucose, insulin and C-peptide concentrations were measured regularly for 3 h. The results of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of L-arabinose added to sucrose drinks when L-arabinose was mixed in a solid or semi-solid mixed meal.

Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects--a randomised open-label cross-over study.

PubMed

Sakurai, Y; Mori, Y; Okamoto, H; Nishimura, A; Komura, E; Araki, T; Shiramoto, M

2015-09-01

Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an alternative to PPIs. To evaluate efficacy, rapidity and duration of acid-inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype. In this randomised, open-label, two-period cross-over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH. Acid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2-33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2-40.4]. The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation. This study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases. © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Influences of OSCE design on students' diagnostic reasoning.

PubMed

Lafleur, Alexandre; Côté, Luc; Leppink, Jimmie

2015-02-01

Some characteristics of assessments exert a strong influence on how students study. Understanding these pre-assessment learning effects is of key importance to the designing of medical assessments that foster students' reasoning abilities. Perceptions of the task demands of an assessment significantly influence students' cognitive processes. However, why and how certain tasks positively 'drive' learning remain unknown. Medical tasks can be assessed as coherent meaningful whole tasks (e.g. examining a patient based on his complaint to find the diagnosis) or can be divided into simpler part tasks (e.g. demonstrating the physical examination of a pre-specified disease). Comparing the benefits of whole-task and part-task assessments in a randomised controlled experiment could guide the design of 'assessments for learning'. The purpose of this study was to determine whether the knowledge that an objective structured clinical examination (OSCE) will contain whole tasks, as opposed to part tasks, increases the use of diagnostic reasoning by medical students when they study for this assessment. In this randomised, controlled, mixed-methods experiment, 40 medical students were randomly paired and filmed while studying together for two imminent physical examination OSCE stations. Each 25-minute study period began with video cues and ended with a questionnaire on cognitive loads. Cues disclosed either a part-task OSCE station (examination of a healthy patient) or a whole-task OSCE station (hypothesis-driven physical examination [HDPE]). In a crossover design, sequences were randomised for both task and content (shoulder or spine). Two blinded and independent authors scored all 40 videos in distinct randomised orders, listening to participants studying freely. Mentioning a diagnosis in association with a sign was scored as a backward association, and the opposite was scored as a forward association; both revealed the use of diagnostic reasoning. Qualitative data were obtained through group interviews. Studying for whole-task OSCE stations resulted in a greater use of diagnostic reasoning. Qualitative data triangulate these findings and show the precedence of cues sourced from the 'student grapevine'. In comparison with 'traditional' part-task OSCEs, whole-task OSCEs like the HDPE increase students' use of diagnostic reasoning during study time. © 2015 John Wiley & Sons Ltd.

[The CASS-CHOU study of mesenteric angina. The comparative effects of cassoulet and sauerkraut with sausages].

PubMed

Danchin, N; Juillière, Y; de la Chaise, A T; Selton-Suty, C

1999-04-01

The goal of study was evaluate in 1,837 consecutive patients the comparative effects of French cassoulet (CASS) and international sauerkraut (CHOU). After procedures of exclusion classical, 8 patients could be evaluated and received in a randomised, doubleblind, crossover protocol an mouth dose of 22.5 g/kg of CASS or CHOU. The results show a very significative difference between the 2 products. A regular absorption of couscous is therefore recommended.

Preference for gel over suppository as delivery vehicle for a rectal microbicide: results of a randomised, crossover acceptability trial among men who have sex with men.

PubMed

Carballo-Diéguez, A; Dolezal, C; Bauermeister, J A; O'Brien, W; Ventuneac, A; Mayer, K

2008-11-01

To assess whether men who have sex with men (MSM) prefer a gel or a suppository as a delivery vehicle for a rectal microbicide. 77 HIV-negative MSM with a recent history of inconsistent condom use during receptive anal intercourse (RAI) who acknowledged being at risk of contracting HIV were enrolled in a randomised, crossover acceptability trial. They compared 35 ml placebo gel with 8 g placebo rectal suppositories used on up to three RAI occasions each. Participants preferred the gel over the suppository (75% versus 25%, p<0.001) and so did their partners (71% versus 29%, p<0.001). The gel received more favourable ratings overall and on attributes such as colour, smell, consistency, feeling in rectum immediately after insertion and/or 30 minutes after insertion and application process. The gel resulted in less negative ratings in terms of participants being bothered by leakage, soiling, bloating, gassiness, stomach cramps, urge to have bowel movement, diarrhoea, pain or trauma. Participants liked the gel more in terms of feelings during anal sex, sexual satisfaction, partners' sexual satisfaction and liking the product when condoms were used and when condoms were not used. In this sample taken from one of the populations most likely to benefit from rectal microbicide availability, gel had greater acceptability than a suppository as a potential microbicide vehicle.

Effect of shortened sleep on energy expenditure, core body temperature, and appetite: a human randomised crossover trial.

PubMed

Hibi, Masanobu; Kubota, Chie; Mizuno, Tomohito; Aritake, Sayaka; Mitsui, Yuki; Katashima, Mitsuhiro; Uchida, Sunao

2017-01-10

The effects of sleep restriction on energy metabolism and appetite remain controversial. We examined the effects of shortened sleep duration on energy metabolism, core body temperature (CBT), and appetite profiles. Nine healthy men were evaluated in a randomised crossover study under two conditions: a 3.5-h sleep duration and a 7-h sleep duration for three consecutive nights followed by one 7-h recovery sleep night. The subjects' energy expenditure (EE), substrate utilisation, and CBT were continually measured for 48 h using a whole-room calorimeter. The subjects completed an appetite questionnaire every hour while in the calorimeter. Sleep restriction did not affect total EE or substrate utilisation. The 48-h mean CBT decreased significantly during the 3.5-h sleep condition compared with the 7-h sleep condition (7-h sleep, 36.75 ± 0.11 °C; 3.5-h sleep, 36.68 ± 0.14 °C; p = 0.016). After three consecutive nights of sleep restriction, fasting peptide YY levels and fullness were significantly decreased (p = 0.011), whereas hunger and prospective food consumption were significantly increased, compared to those under the 7-h sleep condition. Shortened sleep increased appetite by decreasing gastric hormone levels, but did not affect EE, suggesting that greater caloric intake during a shortened sleep cycle increases the risk of weight gain.

A randomised crossover study comparing bimatoprost and latanoprost in subjects with primary angle closure glaucoma.

PubMed

How, A C S; Kumar, R S; Chen, Y-M; Su, D H; Gao, H; Oen, F T; Ho, C-L; Seah, S K; Aung, T

2009-06-01

To compare the intraocular pressure (IOP) lowering efficacy and side effects of latanoprost 0.005% and bimatoprost 0.03% in subjects with chronic primary angle closure glaucoma (PACG). This was an observer-masked randomised crossover study of 60 PACG subjects who received either latanoprost or bimatoprost for 6 weeks, after which they were crossed over to the other medication for another 6 weeks. The IOP-reducing effect of the medications was assessed by the reduction in IOP after 6 weeks of treatment compared with baseline. Fifty-four subjects (80 eyes) completed the study. Latanoprost reduced IOP (mean (SD)) by 8.4 (3.8) mm Hg and bimatoprost by 8.9 (3.9) mm Hg from a baseline of 25.2 (3.6) mm Hg and 25.2 (3.6) mm Hg respectively (p = 0.23). Adverse events were mild in both groups; however there were twice as many reports of an adverse event in the bimatoprost group (81%) compared with the latanoprost group (40%, p<0.01). Ocular irritation was the most frequently reported adverse event in both groups; 22 subjects (37.9%) treated with bimatoprost experienced ocular hyperaemia as compared with 13 subjects (22.4%) treated with latanoprost (p = 0.11). Bimatoprost once daily was similarly effective in reducing IOP compared with latanoprost once daily in subjects with chronic PACG. Both drugs were well tolerated with mild ocular adverse events.

Effect of "preoperative" oral carbohydrate treatment on insulin action--a randomised cross-over unblinded study in healthy subjects.

PubMed

Svanfeldt, Monika; Thorell, Anders; Hausel, Jonatan; Soop, Mattias; Nygren, Jonas; Ljungqvist, Olle

2005-10-01

Preoperative intake of a clear carbohydrate-rich drink reduces insulin resistance after surgery. In this study, we evaluated whether this could be related to increased insulin sensitivity at the onset of surgery. Furthermore, we aimed to establish the optimal dose-regimen. Six healthy volunteers underwent hyperinsulinaemic (0.8 mU/kg/min), normoglycaemic (4.5 mmol/l) clamps and indirect calorimetry on four occasions in a crossover-randomised order; after overnight fasting (CC), after a single evening dose (800 ml) of the drink (LC), after a single morning dose (400 ml, CL) and after intake of the drink in the evening and in the morning before the clamp (LL). Data are presented as mean+/-SD. Statistical analysis was performed using the Student's t-test and ANOVA. Insulin sensitivity was higher in CL and LL (9.2+/-1.5 and 9.3+/-1.9 mg/kg/min, respectively) compared to CC and LC (6.1+/-1.6 and 6.6+/-1.9 mg/kg/min, P<0.01 vs. CL and LL). A carbohydrate-rich drink enhances insulin action 3 h later by approximately 50%. Enhanced insulin action to normal postprandial day-time level at the time of onset of anaesthesia or surgery is likely to, at least partly, explain the effects on postoperative insulin resistance.

Aquatic Exercise Training is Effective in Maintaining Exercise Performance in Trained Heart Failure Patients: A Randomised Crossover Pilot Trial.

PubMed

Adsett, Julie; Morris, Norman; Kuys, Suzanne; Hwang, Rita; Mullins, Robert; Khatun, Mohsina; Paratz, Jennifer; Mudge, Alison

2017-06-01

Providing flexible models and a variety of exercise options are fundamental to supporting long-term exercise participation for patients with heart failure (HF). The aim of this pilot study was to determine the feasibility and efficacy of aquatic exercise training during a maintenance phase for a clinical heart failure population. In this 2 x 2 crossover design trial, individuals who had previously completed HF rehabilitation were randomised into either a land-based or aquatic training program once per week for six weeks, after which time they changed to the alternate exercise training protocol for an additional six weeks. Six-minute walk test (6MWT), grip strength, walk speed, and measures of balance were compared for the two training protocols. Fifty-one participants (43 males, mean age 69.2 yrs) contributed data for the analysis. Both groups maintained function during the follow-up period, however improvements in 6MWT were greater in the land-based training group (95% CI: 0.7, 22.5; p=0.038), by a mean difference of 10.8 metres. No significant difference was observed for other parameters when the two training protocols were compared. Attending an aquatic exercise program once per week is feasible for patients with stable HF and may provide a suitable option to maintain functional performance in select patients. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Effect of lean red meat from lamb v. lean white meat from chicken on the serum lipid profile: a randomised, cross-over study in women.

PubMed

Mateo-Gallego, Rocio; Perez-Calahorra, Sofia; Cenarro, Ana; Bea, Ana M; Andres, Eva; Horno, Jaime; Ros, Emilio; Civeira, Fernando

2012-05-01

The main dietary guidelines recommend restricting total and saturated fat intake in the management of high blood cholesterol levels for cardiovascular risk. These recommendations are usually oversimplified by considering that all red meats should be limited and replaced by white meats. However, lean red meat can be as low in fat as white meat. We examined the effects of red meat (lean breed lamb) and lean white meat (chicken) intake on the lipid profile of a group of women with stable life conditions (nuns living in convents). An open-label, randomised, cross-over study was carried out in thirty-six nuns who consumed either lamb or chicken three times per week for 5-week periods with their usual diet. Clinical, dietary and biochemical variables were evaluated at baseline and the end of each diet period. A validated FFQ was used to assess nutrient intake and monitor compliance. The results showed neither between-diet differences in lipid responses nor differences from baseline in total cholesterol, LDL-cholesterol or TAG for any diet period. In conclusion, consumption of lean red meat (lamb) or lean white meat (chicken) as part of the usual diet is associated with a similar lipid response. These two foods can be exchanged in a healthy diet to increase palatability.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults

PubMed Central

Chambers, Edward S; Viardot, Alexander; Psichas, Arianna; Morrison, Douglas J; Murphy, Kevin G; Zac-Varghese, Sagen E K; MacDougall, Kenneth; Preston, Tom; Tedford, Catriona; Finlayson, Graham S; Blundell, John E; Bell, Jimmy D; Thomas, E Louise; Mt-Isa, Shahrul; Ashby, Deborah; Gibson, Glen R; Kolida, Sofia; Dhillo, Waljit S; Bloom, Stephen R; Morley, Wayne; Clegg, Stuart; Frost, Gary

2015-01-01

Objective The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. Design To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. Results Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. Trial registration number NCT00750438. PMID:25500202

Nefopam, a non-opioid analgesic, does not alleviate experimental work/effort dyspnoea in healthy humans: A randomised controlled trial.

PubMed

Dangers, Laurence; Laviolette, Louis; Charbit, Bény; Similowski, Thomas; Morélot-Panzini, Capucine

2016-08-01

Dyspnoea is a distressing and debilitating symptom with a major impact on quality of life. Alleviation of dyspnoea therefore constitutes a major clinical challenge. When causative physiological disorders cannot be corrected ("persistent dyspnoea"), nonspecific treatment must be considered. Morphine alleviates dyspnoea but has numerous side-effects including ventilatory depression, which justifies looking for alternatives. Certain forms of dyspnoea involve C-fibres, and can be attenuated by C-fibres blockade. We hypothesised that nefopam, a non-sedative benzoxazocine analgesic known to block the transient receptor potential vanilloid subtype 1 abundantly present on C-fibres, would attenuate dyspnoea. We conducted a randomised, double-blind, placebo-controlled crossover study of nefopam in healthy subjects submitted to experimental work/effort dyspnoea by inspiratory threshold loading (15 healthy male volunteers; age 23-41). We studied a perceptual outcome (dyspnoea visual analogue scale -D-VAS-) and a neurophysiological outcome (effect of nefopam on dyspnoea-pain counter-irritation as assessed by laser-evoked potentials; an effect of nefopam on dyspnoea was hypothetised to reduce the ability of dyspnoea to inhibit pain). Somaesthetic evoked potentials (SEPs) were studied as a control. A statistically significant decrease in LEP amplitude was observed in response to loading with nefopam (F = 19.1; p < 0.001) and placebo (F = 5.73 and p < 0.001), with no significant difference between nefopam and placebo and no change in SEP characteristics. In this study, nefopam did not exhibit any effects on dyspnoea. Copyright © 2016 Elsevier Ltd. All rights reserved.

Surgery versus conservative treatment in patients with type A distal radius fractures, a randomized controlled trial

PubMed Central

2014-01-01

Background Fractures of the distal radius are common and account for an estimated 17% of all fractures diagnosed. Two-thirds of these fractures are displaced and require reduction. Although distal radius fractures, especially extra-articular fractures, are considered to be relatively harmless, inadequate treatment may result in impaired function of the wrist. Initial treatment according to Dutch guidelines consists of closed reduction and plaster immobilisation. If fracture redisplacement occurs, surgical treatment is recommended. Recently, the use of volar locking plates has become more popular. The aim of this study is to compare the functional outcome following surgical reduction and fixation with a volar locking plate with the functional outcome following closed reduction and plaster immobilisation in patients with displaced extra-articular distal radius fractures. Design This single blinded randomised controlled trial will randomise between open reduction and internal fixation with a volar locking plate (intervention group) and closed reduction followed by plaster immobilisation (control group). The study population will consist of all consecutive adult patients who are diagnosed with a displaced extra-articular distal radius fracture, which has been adequately reduced at the Emergency Department. The primary outcome (functional outcome) will be assessed by means of the Disability Arm Shoulder Hand Score (DASH). Secondary outcomes comprise the Patient-Rated Wrist Evaluation score (PRWE), quality of life, pain, range of motion, radiological parameters, complications and cross-overs. Since the treatment allocated involves a surgical procedure, randomisation status will not be blinded. However, the researcher assessing the outcome at one year will be unaware of the treatment allocation. In total, 90 patients will be included and this trial will require an estimated time of two years to complete and will be conducted in the Academic Medical Centre Amsterdam and its partners of the regional trauma care network. Dicussion Ideally, patients would be randomised before any kind of treatment has been commenced. However, we deem it not patient-friendly to approach possible participants before adequate reduction has been obtained. Trial registration This study is registered at the Netherlands Trial Register (NTR3113) and was granted permission by the Medical Ethical Review Committee of the Academic Medical Centre on 01-10-2012. PMID:24642190

Active versus passive humidification for self-ventilating tracheostomy and laryngectomy patients: a systematic review of the literature.

PubMed

Wong, C Y Y; Shakir, A A; Farboud, A; Whittet, H B

2016-12-01

To determine whether active or passive humidification methods are more effective in preventing pulmonary complications in self-ventilating neck breather patients. Systematic Review adhering to PRISMA guidance (checklist sourced from www.equator-network.org/). Review of current published relevant literature at a tertiary department of Otolaryngology and Head & Neck Surgery. We included all separate studies and comparison studies of active and passive humidification techniques in adult and paediatric neck breather patients. The primary outcome is the reduction in pulmonary complications. Secondary outcomes include patient compliance; carer and user satisfaction. Seven studies were included in this review: two RCTs (133 patients), one randomised controlled cross-over trial (29 patients), three randomised prospective studies (171 patients), and one retrospective study (73 patients). Only one study was conducted on paediatric neck breathers. The overall quality of the studies was low. Five studies were at a high risk of bias. Of the remaining two studies, one study had a low risk of bias and the other had an unclear risk. Despite limited subject evidence, results show that passive methods of humidification (mainly HME) is the preferred choice of humidification in the spontaneously breathing neck breather patients group mainly due to the reduction in pulmonary complaints, and better patient compliance. © 2015 John Wiley & Sons Ltd.

Pharmacological interventions for sleepiness and sleep disturbances caused by shift work.

PubMed

Liira, Juha; Verbeek, Jos H; Costa, Giovanni; Driscoll, Tim R; Sallinen, Mikael; Isotalo, Leena K; Ruotsalainen, Jani H

2015-02-01

Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality. To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst of work, or both, in workers undertaking shift work. We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews. We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while of work, alertness and sleepiness, or fatigue at work. Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate. We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined caffeine plus naps to decrease sleepiness or to increase alertness.

Double-blind randomised controlled trial of the independent and synergistic effect of Spirulina maxima with exercise (ISESE) on general fitness, lipid profile and redox status in overweight and obese subjects: study protocol

PubMed Central

Hernández-Lepe, Marco Antonio; López-Díaz, José Alberto; de la Rosa, Laura Alejandra; Hernández-Torres, Rosa Patricia; Wall-Medrano, Abraham; Juarez-Oropeza, Marco Antonio; Pedraza-Chaverri, José; Urquidez-Romero, Rene; Ramos-Jiménez, Arnulfo

2017-01-01

Introduction In order to reduce cardiovascular disease risk factors, a healthy diet must include dietary antioxidants from different sources (eg, Spirulina maxima) and regular practice of exercise should be promoted. There is some evidence from animal studies that S. maxima and exercise decrease cardiovascular disease risks factors. However, very few studies have proved the independent or synergistic effect of S. maxima plus exercise in humans. This study attempts to address the independent and synergistic effects in overweight and obese subjects participating in a systematic physical exercise programme at moderate intensity on general fitness, plasma lipid profile and antioxidant capacity. Methods and analysis Using a randomised, double-blind, placebo-controlled, counterbalanced crossover study design, 80 healthy overweight and obese subjects will be evaluated during a 12-week isoenergetic diet accompanied by 4.5 g/day S. maxima intake and/or a physical systematic exercise programme at moderate intensity. Body composition, oxygen uptake, heart rate, capillary blood lactate, plasma concentrations of triacylglycerols, total, low-density and high-density lipoprotein cholesterol, antioxidant status, lipid oxidation, protein carbonyls, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione reductase and paraoxonase will be assessed. Ethics and dissemination This study and all the procedures have been approved by the Universidad Autonoma de Ciudad Juarez Bioethics Committee. Findings will be disseminated through peer-reviewed journals, national and international conferences. Trial registration number ClinicalTrials.gov: NCT02837666. PMID:28645949

Effect of whole-body mild-cold exposure on arterial stiffness and central haemodynamics: a randomised, cross-over trial in healthy men and women.

PubMed

King, Sibella G; Ahuja, Kiran D K; Wass, Jezreel; Shing, Cecilia M; Adams, Murray J; Davies, Justin E; Sharman, James E; Williams, Andrew D

2013-05-01

Aortic pulse wave velocity (PWV) and augmentation index (AIx) are independent predictors of cardiovascular risk and mortality, but little is known about the effect of air temperature changes on these variables. Our study investigated the effect of exposure to whole-body mild-cold on measures of arterial stiffness (aortic and brachial PWV), and on central haemodynamics [including augmented pressure (AP), AIx], and aortic reservoir components [including reservoir and excess pressures (P ex)]. Sixteen healthy volunteers (10 men, age 43 ± 19 years; mean ± SD) were randomised to be studied under conditions of 12 °C (mild-cold) and 21 °C (control) on separate days. Supine resting measures were taken at baseline (ambient temperature) and after 10, 30, and 60 min exposure to each experimental condition in a climate chamber. There was no significant change in brachial blood pressure between mild-cold and control conditions. However, compared to control, AP [+2 mmHg, 95 % confidence interval (CI) 0.36-4.36; p = 0.01] and AIx (+6 %, 95 % CI 1.24-10.1; p = 0.02) increased, and time to maximum P ex (a component of reservoir function related to timing of peak aortic in-flow) decreased (-7 ms, 95 % CI -15.4 to 2.03; p = 0.01) compared to control. Yet there was no significant change in aortic PWV (+0.04 m/s, 95 % CI -0.47 to 0.55; p = 0.87) or brachial PWV (+0.36 m/s; -0.41 to 1.12; p = 0.35) between conditions. We conclude that mild-cold exposure increases central haemodynamic stress and alters timing of peak aortic in-flow without differentially affecting arterial stiffness.

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

PubMed Central

Farr, Olivia M.; Sofopoulos, Michail; Tsoukas, Michael A.; Dincer, Fadime; Thakkar, Bindiya; Sahin-Efe, Ayse; Filippaios, Andreas; Bowers, Jennifer; Srnka, Alexandra; Gavrieli, Anna; Ko, Byung-Joon; Liakou, Chrysoula; Kanyuch, Nickole; Tseleni-Balafouta, Sofia; Mantzoros, Christos S.

2016-01-01

Aims/hypothesis Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrollment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. PMID:26831302

Recruitment and retention of young women into nutrition research studies: practical considerations.

PubMed

Leonard, Alecia; Hutchesson, Melinda; Patterson, Amanda; Chalmers, Kerry; Collins, Clare

2014-01-16

Successful recruitment and retention of participants into research studies is critical for optimising internal and external validity. Research into diet and lifestyle of young women is important due to the physiological transitions experienced at this life stage. This paper aims to evaluate data related to recruitment and retention across three research studies with young women, and present practical advice related to recruiting and retaining young women in order to optimise study quality within nutrition research. Recruitment and retention strategies used in three nutrition studies that targeted young women (18 to 35 years) were critiqued. A randomised controlled trial (RCT), a crossover validation study and a cross-sectional survey were conducted at the University of Newcastle, Australia between 2010 and 2013Successful recruitment was defined as maximum recruitment relative to time. Retention was assessed as maximum participants remaining enrolled at study completion. Recruitment approaches included notice boards, web and social network sites (Facebook and Twitter), with social media most successful in recruitment. The online survey had the highest recruitment in the shortest time-frame (751 participants in one month). Email, phone and text message were used in study one (RCT) and study two (crossover validation) and assisted in low attrition rates, with 93% and 75.7% completing the RCT and crossover validation study respectively. Of those who did not complete the RCT, reported reasons were: being too busy; and having an unrelated illness. Recruiting young women into nutrition research is challenging. Use of social media enhances recruitment, while Email, phone and text message contact improves retention within interventions. Further research comparing strategies to optimise recruitment and retention in young women, including flexible testing times, reminders and incentives is warranted.

The effectiveness and safety of combining varenicline with nicotine e-cigarettes for smoking cessation in people with mental illnesses and addictions: study protocol for a randomised-controlled trial.

PubMed

Bullen, Chris; Verbiest, Marjolein; Galea-Singer, Susanna; Kurdziel, Tomasz; Laking, George; Newcombe, David; Parag, Varsha; Walker, Natalie

2018-05-04

Smoking rates are higher in New Zealand (NZ) adults with mental illnesses and alcohol and other drug (AOD) addictions, compared to the overall population. Quit attempts using "gold standard" smoking cessation treatments often fail in people with these conditions, so more flexible treatment regimens that adapt to a person's responsiveness to treatment are worth investigating. The STATUS trial aims to evaluate the effectiveness and safety of combining varenicline with nicotine e-cigarettes for smoking cessation among varenicline non-responders in treatment for mental health illnesses and/or AOD addictions. This is a pragmatic two-arm, open-label, randomised trial. Participants will be daily smokers using mental health and/or addiction services in Auckland, aged ≥18 years, motivated to quit smoking, and eligible to access varenicline through the NZ special authority process. After 2 weeks of using varenicline plus behavioural support, participants who have not reduced their daily smoking by ≥50% will be randomised (1:1) to either 10 weeks of continued varenicline use or 10 weeks of varenicline plus an 18 mg/mL nicotine e-cigarette. All participants will receive weekly withdrawal-orientated behavioural support calls for 6 weeks post-randomisation. The primary outcome is self-reported biochemically-verified (exhaled carbon monoxide) continuous abstinence at 24 weeks post-randomisation. Secondary outcomes, measured at six, 12 and 24 weeks post-randomisation include: self-reported continuous abstinence, 7-day point prevalence abstinence, smoking reduction, time to relapse, cross-over, use of other smoking cessation support, serious adverse events, treatment adherence, compliance, acceptability, dual use, continuation of treatment use, mental illness symptoms and AOD use, health-related quality of life, and cost-analysis. A sample size of 338 will confer 80% power (p = 0.05) to detect a 15% absolute difference between the varenicline alone and varenicline plus e-cigarette groups. People with mental illness and/or AOD addictions are just as motivated as others to quit smoking, but are less likely to succeed. Adapting smoking cessation medication after a lack of responsiveness in the first 2 weeks of initial treatment in this priority population by adding a nicotine e-cigarette may be one way to increase long-term quit rates. Australian NZ Clinical Trial Registry: ACTRN12616001355460 (29 September 2016).

Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea

PubMed Central

Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

2011-01-01

Objective To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). Design An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline ‘trigger meals’ and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. Setting Outpatient internal medicine practice clinic. Patients 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised ‘food triggers’, no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11–30 years and 16% for more than 40 years. Interventions After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. Main outcome measures The primary analysis was number of patients who chose PEZ over placebo for the extended use. Results Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. Conclusions PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation. PMID:22095308

Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.

PubMed

Krarup, A L; Ny, L; Astrand, M; Bajor, A; Hvid-Jensen, F; Hansen, M B; Simrén, M; Funch-Jensen, P; Drewes, A M

2011-05-01

Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor 'transient receptor potential vanilloid 1'(TRPV1) are a potential drug class for GERD treatment. To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Twenty-two healthy men (20-31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. intention-to-treat. A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10-38%] and 28%, respectively (CI: 14-43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1-3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0-5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported 'feeling cold' and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4±0.3 °C and 0.7±0.3 °C, respectively, P<0.05). AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD. © 2011 Blackwell Publishing Ltd.

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients.

PubMed

Sweis, R; Kaufman, E; Anggiansah, A; Wong, T; Dettmar, P; Fried, M; Schwizer, W; Avvari, R K; Pal, A; Fox, M

2013-06-01

Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. MRI visualized a "mass" of GA form at the oesophago-gastric junction (OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome. © 2013 Blackwell Publishing Ltd.

Effects of breaking up sitting on adolescents' postprandial glucose after consuming meals varying in energy: a cross-over randomised trial.

PubMed

Fletcher, Elly A; Salmon, Jo; McNaughton, Sarah A; Orellana, Liliana; Wadley, Glenn D; Bruce, Clinton; Dempsey, Paddy C; Lacy, Kathleen E; Dunstan, David W

2018-03-01

To explore the impact of uninterrupted sitting versus sitting with resistance-type activity breaks on adolescents' postprandial glucose responses while consuming a diet varying in energy. Cross-over randomised trial. Thirteen healthy participants (16.4±1.3years) completed a four-treatment cross-over trial: (1) uninterrupted sitting+high-energy diet; (2) sitting with breaks+high-energy diet; (3) uninterrupted sitting+standard-energy diet; and (4) sitting with breaks+standard-energy diet. For all four conditions, two identical meals were consumed; at 0h and 3h. A continuous glucose monitoring system (CGM) recorded interstitial glucose concentrations every five minutes. Linear mixed models examined differences in glucose positive incremental area under the curve (iAUC) and total AUC between the sitting and diet conditions for the first meal, second meal and entire trial period. Compared to the uninterrupted sitting conditions, the breaks condition elicited a 36.0mmol/L/h (95%CI 6.6-65.5) and 35.9mmol/L/h (95%CI 6.6-65.5) lower iAUC response after the first and second meal, respectively, but not for the entire trial period or for total AUC. Compared to the standard-energy diet, the high-energy diet elicited a 55.0mmol/L/h (95%CI 25.8-84.2) and 75.7mmol/L/h (95%CI 8.6-142.7) higher iAUC response after the first meal and entire trial, respectively. Similar response to the high-energy diet were observed for total AUC. According to iAUC, interrupting sitting had a significant effect on lowering postprandial glucose for both dietary conditions, however, it was not significant when examining total AUC. Larger studies are needed to confirm these findings. ACTRN12615001145594. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Dark chocolate: consumption for pleasure or therapy?

PubMed

Lippi, Giuseppe; Franchini, Massimo; Montagnana, Martina; Favaloro, Emmanuel J; Guidi, Gian Cesare; Targher, Giovanni

2009-11-01

Traditional chocolate is derived from the cocoa bean, which is one of the most concentrated sources of flavanols, a subgroup of the natural antioxidant plant compounds called flavonoids. Accumulating evidence from the past 10 years demonstrates that moderate consumption of chocolate, especially dark chocolate, may exert protective effects against the development of cardiovascular disease. Several mechanisms have been proposed to explain this positive influence, including metabolic, antihypertensive, anti-inflammatory, and anti-thrombotic effects, as well as effects on insulin sensitivity and vascular endothelial function. Should these results be confirmed in randomised, controlled, cross-over, multi-dose trials, then the pleasure associated with chocolate consumption might also be justified from health and psychological perspectives. However, since dark chocolate has substantially higher levels of flavonoids than milk chocolate, and milk proteins may inhibit absorption of flavonoids, it might be preferable to consume dark chocolate than the white (milk) variety.

[Reduced pain from osteoarthritis in hip joint or knee joint during treatment with calcium ascorbate. A randomized, placebo-controlled cross-over trial in general practice].

PubMed

Jensen, Niels Hertz

2003-06-16

Although vitamin C is essential for the formation of collagen and proteoglycan and has been shown to minimise surgically induced arthritis in guinea pigs, no controlled trial has examined its effect on human osteoarthritis. The trial was a multicenter, double-blind, randomised, placebo-controlled, crossover-trial performed by ten general practitioners. The Declaration of Helsinki and the European guidelines for good clinical practice were strictly followed. One hundred and thirty-three patients with radiographically verified symptomatic osteoarthritis of the hip joints and/or the knee joints were treated with one gram of calcium ascorbate or identically looking placebo tablets. The calcium ascorbate tablets and the placebo tablets should be swallowed daily for 14 +/- 3 days respectively, separated by 7 +/- 3 days wash out. The main outcome measure was difference on the 100 mm visual analog scale (VAS) score for pain in a preselected joint. The secondary outcomes were Lequesne score for function and patient preference. Calculated on an intention-to-treat principle, calcium ascorbate reduced pain significantly compared to placebo (p = 0.0078 by analysis of variance between groups (ANOVA) for difference in VAS, mean difference 4.6 mm (95% CI 1.2-8.0). Similar superiority was found for Lequesne index (p = 0.036, difference 0.56 (95% CI 0.04-1.08) and for patient preference (p = 0.012). The demonstrated effect is less than half as pronounced as commonly reported for NSAID etc. If the finding can be reproduced with a smaller, acceptable intake of vitamin C this would be of importance considering the large prevalence of osteoarthrosis.

Bupropion for the treatment of apathy in Huntington’s disease: A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

PubMed Central

Gelderblom, Harald; Wüstenberg, Torsten; McLean, Tim; Mütze, Lisanne; Fischer, Wilhelm; Saft, Carsten; Hoffmann, Rainer; Süssmuth, Sigurd; Schlattmann, Peter; van Duijn, Erik; Landwehrmeyer, Bernhard; Priller, Josef

2017-01-01

Objective To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington’s disease (HD). Methods In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy—Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). Results At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. Conclusion Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. Trial registration ClinicalTrials.gov 01914965 PMID:28323838

Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial.

PubMed

Goebel, Andreas; Baranowski, Andrew; Maurer, Konrad; Ghiai, Artemis; McCabe, Candy; Ambler, Gareth

2010-02-02

Treatment of long-standing complex regional pain syndrome (CRPS) is empirical and often of limited efficacy. Preliminary data suggest that the immune system is involved in sustaining this condition and that treatment with low-dose intravenous immunoglobulin (IVIG) may substantially reduce pain in some patients. To evaluate the efficacy of IVIG in patients with longstanding CRPS under randomized, controlled conditions. A randomized, double-blind, placebo-controlled crossover trial. (National Research Registry number: N0263177713; International Standard Randomised Controlled Trial Number Registry: 63918259) University College London Hospitals Pain Management Centre. Persons who had pain intensity greater than 4 on an 11-point (0 to 10) numerical rating scale and had CRPS for 6 to 30 months that was refractory to standard treatment. IVIG, 0.5 g/kg, and normal saline in separate treatments, divided by a washout period of at least 28 days. The primary outcome was pain intensity 6 to 19 days after the initial treatment and the crossover treatment. 13 eligible participants were randomly assigned between November 2005 and May 2008; 12 completed the trial. The average pain intensity was 1.55 units lower after IVIG treatment than after saline (95% CI, 1.29 to 1.82; P < 0.001). In 3 patients, pain intensity after IVIG was less than after saline by 50% or more. No serious adverse reactions were reported. The trial was small, and recruitment bias and chance variation could have influenced results and their interpretation. IVIG, 0.5 g/kg, can reduce pain in refractory CRPS. Studies are required to determine the best immunoglobulin dose, the duration of effect, and when repeated treatments are needed. Association of Anaesthetists of Great Britain and Ireland, University College London Hospitals Charity, and CSL-Behring.

Effects of pressure applied during standardized spinal mobilizations on peripheral skin blood flow: A randomised cross-over study.

PubMed

Zegarra-Parodi, Rafael; Pazdernik, Vanessa K; Roustit, Matthieu; Park, Peter Yong Soo; Degenhardt, Brian F

2016-02-01

Peripheral skin blood flow (SBF) changes during and after spinal mobilization (SM), evaluated with laser Doppler flowmetry, may document physiological responses associated with SM. To document variations in SBF during and after application of an SM and evaluate influence of pressure on SBF by applying the same standardized SM with 3 different nonnoxious pressures. Cross-over design with 4 interventions on 4 different days: control (no touch) and 3 SMs applied rhythmically at 5%, 40%, or 80% of pain pressure threshold (sham SM, low-pressure SM, or high-pressure SM, respectively). Thirty-two individuals participated. The inspiratory gasp (IG) test was our positive control of vasoconstriction through excitation of the skin sympathetic nervous activity (SSNA). Each session comprised 5 phases: (1) baseline at the end of a 20-min acclimatization, (2) IG test, (3) post-IG phase, (4) SM phase or no manual contact for control, and (5) post-SM phase. A Biopac MP36 system collected SBF data, and a Novel Pliance-X system recorded pressure data. Equal and significant bilateral vasodilation occurred during application of unilateral sham SM, low-pressure SM, and high-pressure SM. Post-SM significant vasodilation persisted after high-pressure SM. The current study is the first to describe bilateral peripheral SBF changes occurring during and 5 min after application of standardized SMs. Our post-SM vasodilation suggests involvement of mechanisms other than the putative SSNA-excitatory mechanism proposed with skin conductance measurements. Persistence of post-SM vasodilation following only high-pressure SM suggests possible pressure-dependent mechanisms. However, further research is warranted to clarify our findings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial.

PubMed

Haidar, Ahmad; Legault, Laurent; Messier, Virginie; Mitre, Tina Maria; Leroux, Catherine; Rabasa-Lhoret, Rémi

2015-01-01

The artificial pancreas is an emerging technology for the treatment of type 1 diabetes and two configurations have been proposed: single-hormone (insulin alone) and dual-hormone (insulin and glucagon). We aimed to delineate the usefulness of glucagon in the artificial pancreas system. We did a randomised crossover trial of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy (continuous subcutaneous insulin infusion) in participants aged 12 years or older with type 1 diabetes. Participants were assigned in a 1:1:1:1:1:1 ratio with blocked randomisation to the three interventions and attended a research facility for three 24-h study visits. During visits when the patient used the single-hormone artificial pancreas, insulin was delivered based on glucose sensor readings and a predictive dosing algorithm. During dual-hormone artificial pancreas visits, glucagon was also delivered during low or falling glucose. During conventional insulin pump therapy visits, patients received continuous subcutaneous insulin infusion. The study was not masked. The primary outcome was the time for which plasma glucose concentrations were in the target range (4·0-10·0 mmol/L for 2 h postprandially and 4·0-8·0 mmol/L otherwise). Hypoglycaemic events were defined as plasma glucose concentration of less than 3·3 mmol/L with symptoms or less than 3·0 mmol/L irrespective of symptoms. Analysis was by modified intention to treat, in which we included data for all patients who completed at least two visits. A p value of less than 0·0167 (0·05/3) was regarded as significant. This trial is registered with ClinicalTrials.gov, number NCT01754337. The mean proportion of time spent in the plasma glucose target range over 24 h was 62% (SD 18), 63% (18), and 51% (19) with single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional insulin pump therapy, respectively. The mean difference in time spent in the target range between single-hormone artificial pancreas and conventional insulin pump therapy was 11% (17; p=0·002) and between dual-hormone artificial pancreas and conventional insulin pump therapy was 12% (21; p=0·00011). There was no difference (15; p=0·75) in the proportion of time spent in the target range between the single-hormone and dual-hormone artificial pancreas systems. There were 52 hypoglycaemic events with conventional insulin pump therapy (12 of which were symptomatic), 13 with the single-hormone artificial pancreas (five of which were symptomatic), and nine with the dual-hormone artificial pancreas (0 of which were symptomatic); the number of nocturnal hypoglycaemic events was 13 (0 symptomatic), 0, and 0, respectively. Single-hormone and dual-hormone artificial pancreas systems both provided better glycaemic control than did conventional insulin pump therapy. The single-hormone artificial pancreas might be sufficient for hypoglycaemia-free overnight glycaemic control. Canadian Diabetes Association; Fondation J A De Sève; Juvenile Diabetes Research Foundation; and Medtronic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1,2-octanediol spray versus placebo.

PubMed

Burgess, Ian F; Brunton, Elizabeth R; French, Rebecca; Burgess, Nazma A; Lee, Peter N

2014-05-30

To determine whether regular use of a spray containing 1,2-octanediol 1%, which has been shown to inhibit survival of head lice, is able to work as a preventive against establishment of new infestations. Randomised, double-blind, cross-over, community study in Cambridgeshire, UK. 63 male and female schoolchildren aged 4-16 years judged to have a high risk of recurrent infestation. Only the youngest member of a household attending school participated. Participants were treated to eliminate lice, randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over to the other spray for 6 weeks. Parents applied the sprays at least twice weekly or more frequently if the hair was washed. Investigators monitored weekly for infestation and replenished supplies of spray. The primary endpoint was the time taken until the first infestation event occurred. The secondary measure was safety of the product in regular use. Intention-to-treat analysis found a total of 32 confirmed infestations in 20 participants, with 9 of them infested while using both products. In these nine participants the time to first infestation showed a significant advantage to 1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the population included was not large enough to demonstrate significance. There were no serious adverse events and only two adverse events possibly related to treatment, one was a case of transient erythema and another of a rash that resolved after 5 days. Routine use of 1% octanediol spray provided a significant level of protection from infestation. It was concluded that this product is effective if applied regularly and thoroughly. ISRCTN09524995. 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 randomised crossover placebo-controlled trial investigating the effect of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) on postchallenge plasma glucose and insulin levels in men and women.

PubMed

Paradis, Marie-Eve; Couture, Patrick; Lamarche, Benoît

2011-12-01

This study examined the impact of brown seaweed on post-load plasma glucose and insulin concentrations in men and women. Twenty-three participants (11 men, 12 women) aged 19-59 years were recruited in this double-blind, randomized, placebo-controlled crossover study. The test product consisted of a commercially available blend of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) with known inhibitory action on α-amylase and α-glucosidase activities (InSea²). Two 250 mg seaweed capsules and 2 placebo capsules were consumed on each occasion 30 min prior to the consumption of 50 g of carbohydrates from bread. Plasma glucose and insulin concentrations were measured over a period of 3 h postcarbohydrate ingestion at predetermined time points. Both treatments were separated by a 1-week washout period. Data were analysed using mixed models for repeated measures. Compared with placebo, consumption of seaweed was associated with a 12.1% reduction in the insulin incremental area under the curve (p = 0.04, adjusted for baseline) and a 7.9% increase in the Cederholm index of insulin sensitivity (p < 0.05). The single ingestion of 500 mg of brown seaweed had no significant effect on the glucose response (p = 0.24, adjusted for baseline). Glucose and insulin responses were similar between men and women. Consumption of the seaweed capsules was not associated with any adverse event. These data suggest that brown seaweed may alter the insulin homeostasis in response to carbohydrate ingestion.

A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects.

PubMed

Costabile, Adele; Kolida, Sofia; Klinder, Annett; Gietl, Eva; Bäuerlein, Michael; Frohberg, Claus; Landschütze, Volker; Gibson, Glenn R

2010-10-01

There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides-Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed. There were no adverse gastrointestinal symptoms apart from a significant increase in mild and moderate bloating upon VLCI ingestion. These observations were also confirmed by in vitro gas production measurements. In conclusion, daily consumption of VLCI extracted from globe artichoke exerted a pronounced prebiotic effect on the human faecal microbiota composition and was well tolerated by all volunteers.

A randomised clinical study to measure the anti-erosion benefits of a stannous-containing sodium fluoride dentifrice

PubMed Central

West, Nicola; Seong, Joon; Macdonald, Emma; He, Tao; Barker, Matthew; Hooper, Susan

2015-01-01

Background: To compare the enamel protection efficacy of stannous-containing sodium fluoride and sodium monofluorophosphate (MFP)/triclosan dentifrices marketed in India in an in situ erosion model with acidic challenge. Materials and Methods: This randomised and controlled, in situ, supervised, double-blind clinical trial employed a two-treatment, four-period crossover design, wherein subjects wore an appliance fitted with human enamel samples 6 h/day during each 10 day treatment period and swished twice daily with their assigned dentifrice slurry: Oral-B® Pro-Health (maximum 1,000 ppm F as sodium fluoride with stannous chloride) or Colgate® Strong Teeth with Cavity Protection (maximum 1,000 F as sodium MFP and triclosan). Subjects swished with 250 ml of orange juice over a 10 min period after each treatment and twice daily for the acidic erosive challenge. Enamel samples were measured for tooth surface loss using contact profilometry at baseline and day 10. Results: A total of 34 subjects were randomised to treatment; 32 subjects completed the final visit. Baseline profilometry measurements of the specimen surfaces were near zero within ± 0.3 μm, and no statistically significant difference (P > 0.48) on average was observed between the two test dentifrices. At day 10, the stannous-containing dentifrice demonstrated 88% less erosion (P < 0.0001) relative to the MFP/triclosan dentifrice. Estimated medians (95% confidence intervals) were 0.21 μm (0.17, 0.25) for the stannous-containing dentifrice versus 1.66 μm (1.39, 1.99) for the MFP/triclosan dentifrice. Both dentifrices were well-tolerated. Conclusions: Compared with MFP/triclosan toothpaste, a stabilised stannous-containing sodium fluoride dentifrice gave statistically significantly greater protection against tooth enamel surface loss in situ following repeated acid erosive challenge. PMID:26015669

A randomised cross-over pharmacokinetic bioavailability study of synthetic versus kiwifruit-derived vitamin C.

PubMed

Carr, Anitra C; Bozonet, Stephanie M; Vissers, Margreet C M

2013-11-11

Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged 18-35 years) received either a chewable tablet (200 mg vitamin C) or the equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold). Fasting blood and urine were collected half hourly to hourly over the eight hours following intervention. The ascorbate content of the plasma and urine was determined using HPLC with electrochemical detection. Plasma ascorbate levels increased from 0.5 h after the intervention (P = 0.008). No significant differences in the plasma time-concentration curves were observed between the two interventions (P = 0.645). An estimate of the total increase in plasma ascorbate indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived vitamin C. There was an increase in urinary ascorbate excretion, relative to urinary creatinine, from two hours post intervention (P < 0.001). There was also a significant difference between the two interventions, with enhanced ascorbate excretion observed in the kiwifruit group (P = 0.016). Urinary excretion was calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic vitamin C.

Effect of shortened sleep on energy expenditure, core body temperature, and appetite: a human randomised crossover trial

PubMed Central

Hibi, Masanobu; Kubota, Chie; Mizuno, Tomohito; Aritake, Sayaka; Mitsui, Yuki; Katashima, Mitsuhiro; Uchida, Sunao

2017-01-01

The effects of sleep restriction on energy metabolism and appetite remain controversial. We examined the effects of shortened sleep duration on energy metabolism, core body temperature (CBT), and appetite profiles. Nine healthy men were evaluated in a randomised crossover study under two conditions: a 3.5-h sleep duration and a 7-h sleep duration for three consecutive nights followed by one 7-h recovery sleep night. The subjects’ energy expenditure (EE), substrate utilisation, and CBT were continually measured for 48 h using a whole-room calorimeter. The subjects completed an appetite questionnaire every hour while in the calorimeter. Sleep restriction did not affect total EE or substrate utilisation. The 48-h mean CBT decreased significantly during the 3.5-h sleep condition compared with the 7-h sleep condition (7-h sleep, 36.75 ± 0.11 °C; 3.5-h sleep, 36.68 ± 0.14 °C; p = 0.016). After three consecutive nights of sleep restriction, fasting peptide YY levels and fullness were significantly decreased (p = 0.011), whereas hunger and prospective food consumption were significantly increased, compared to those under the 7-h sleep condition. Shortened sleep increased appetite by decreasing gastric hormone levels, but did not affect EE, suggesting that greater caloric intake during a shortened sleep cycle increases the risk of weight gain. PMID:28071649

Consumption of a diet rich in Brassica vegetables is associated with a reduced abundance of sulphate‐reducing bacteria: A randomised crossover study

PubMed Central

Kellingray, Lee; Tapp, Henri S.; Saha, Shikha; Doleman, Joanne F.; Narbad, Arjan

2017-01-01

Scope We examined whether a Brassica‐rich diet was associated with an increase in the relative abundance of intestinal lactobacilli and sulphate‐reducing bacteria (SRB), or alteration to the composition of the gut microbiota, in healthy adults. Methods and results A randomised crossover study was performed with ten healthy adults who were fed a high‐ and a low‐Brassica diet for 2‐wk periods, with a 2‐wk washout phase separating the diets. The high‐Brassica diet consisted of six 84 g portions of broccoli, six 84 g portions of cauliflower and six 300 g portions of a broccoli and sweet potato soup. The low‐Brassica diet consisted of one 84 g portion of broccoli and one 84 g portion of cauliflower. Faecal microbiota composition was measured in samples collected following 2‐wk Brassica‐free periods (consumption of all Brassica prohibited), and after each diet, whereby the only Brassica consumed was that supplied by the study team. No significant changes to the relative abundance of lactobacilli were observed (p = 0.8019). The increased consumption of Brassica was associated with a reduction in the relative abundance of SRB (p = 0.0215), and members of the Rikenellaceae, Ruminococcaceae, Mogibacteriaceae, Clostridium and unclassified Clostridiales (p < 0.01). Conclusion The increased consumption of Brassica vegetables was linked to a reduced relative abundance of SRB, and therefore may be potentially beneficial to gastrointestinal health. PMID:28296348

Including pork in the Mediterranean diet for an Australian population: Protocol for a randomised controlled trial assessing cardiovascular risk and cognitive function.

PubMed

Wade, Alexandra T; Davis, Courtney R; Dyer, Kathryn A; Hodgson, Jonathan M; Woodman, Richard J; Keage, Hannah A D; Murphy, Karen J

2017-12-22

The Mediterranean diet is characterised by the high consumption of extra virgin olive oil, fruits, vegetables, grains, legumes and nuts; moderate consumption of fish, poultry, eggs and dairy; and low consumption of red meat and sweets. Cross sectional, longitudinal and intervention studies indicate that a Mediterranean diet may be effective for the prevention of cardiovascular disease and dementia. However, previous research suggests that an Australian population may find red meat restrictions difficult, which could affect long term sustainability of the diet. This paper outlines the protocol for a randomised controlled trial that will assess the cardiovascular and cognitive benefits of a Mediterranean diet modified to include 2-3 weekly serves of fresh, lean pork. A 24-week cross-over design trial will compare a modified Mediterranean diet with a low-fat control diet in at-risk men and women. Participants will follow each of the two diets for 8 weeks, with an 8-week washout period separating interventions. Home measured systolic blood pressure will be the primary outcome measure. Secondary outcomes will include body mass index, body composition, fasting blood lipids, C-reactive protein, fasting plasma glucose, fasting serum insulin, erythrocyte fatty acids, cognitive function, psychological health and well-being, and dementia risk. To our knowledge this research is the first to investigate whether an alternate source of protein can be included in the Mediterranean diet to increase sustainability and feasibility for a non-Mediterranean population. Findings will be significant for the prevention of cardiovascular disease and age-related decline, and may inform individuals, clinicians and public health policy. ACTRN12616001046493 . Registered 5 August 2016.

Remineralisation by chewing sugar-free gums in a randomised, controlled in situ trial including dietary intake and gauze to promote plaque formation.

PubMed

Cochrane, N J; Shen, P; Byrne, S J; Walker, G D; Adams, G G; Yuan, Y; Reynolds, C; Hoffmann, B; Dashper, S G; Reynolds, E C

2012-01-01

Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not. Copyright © 2012 S. Karger AG, Basel.

Eight-day consumption of inulin added to a yogurt breakfast lowers postprandial appetite ratings but not energy intakes in young healthy females: a randomised controlled trial.

PubMed

Heap, Sarah; Ingram, Jessica; Law, Marron; Tucker, Amy J; Wright, Amanda J

2016-01-28

Increasing feelings of satiety may reduce appetite and energy intake. The role of inulin consumption in impacting satiety is unclear. A randomised double-blind controlled crossover trial aimed to determine the effects of inulin+yogurt on satiety after 1 and 8-d consumption. The preload breakfast included 100 g vanilla yogurt with (yogurt-inulin (YI)) and without (yogurt-control (YC)) 6 g inulin. A total of nineteen healthy females (22·8 (sd 2·7) years) with non-restrained eating behaviour and taking hormonal contraceptives participated in the study. Day 1 and 8 visual analogue scale (VAS) ratings of Hunger, Fullness, Desire to Eat and Prospective Food Consumption (PFC) were collected at fasting and every 30 min for 180 min. Energy intake was calculated from a weighed ad libitum lunch and remainder of day food records. Total AUC was calculated for each VAS. Day 1 (VAS only) and 8 (VAS and energy intakes) data were compared between YI and YC using ANCOVA, and ANOVA was used to compare energy intakes on Day 1. There were no significant differences between Day 1 YI and YC AUC appetite ratings or energy intakes. However, 8-d consumption of YI v. YC was associated with lower Desire to Eat and PFC ratings but similar lunch and total day energy intakes. Therefore, the addition of 6 g inulin to a commercially available yogurt affected feelings of appetite, but not energy intake, after repeated consumption. These results suggest that inulin may be a suitable ingredient to increase dietary fibre consumption, with potential to impact appetite.

Do healthy school meals affect illness, allergies and school attendance in 8- to 11-year-old children? A cluster-randomised controlled study.

PubMed

Laursen, R P; Lauritzen, L; Ritz, C; Dyssegaard, C B; Astrup, A; Michaelsen, K F; Damsgaard, C T

2015-05-01

A nutritionally adequate diet in childhood is important for health and resistance of allergies and infections. This study explored the effects of school meals rich in fish, vegetables and fibre on school attendance, asthma, allergies and illness in 797 Danish 8- to 11-year-old children. No comparable studies conducted in high-income settings have been identified. The OPUS School Meal Study was a cluster-randomised cross-over trial. Children from third and fourth grades at nine Danish schools received school meals or usual packed lunch (control) for two 3-month periods. Occurrence and duration of illnesses, asthma and allergies during the last 14 days were recorded by parental questionnaires at baseline and after each 3-month period. Self-reported well-being was assessed by visual analogue scales. The school meals did not affect school attendance, parent-reported occurrence or duration of asthma and allergies or self-reported well-being. The most common symptoms of illness were stomach pain (24%), headache (28%) and cold (24%). A slightly higher number of children experienced headaches in the school meal (27%) compared with the control period (22%) (P=0.02). However, subgroup analyses showed that this effect was only seen in children eating school meals in the classroom (P=0.007), and not in common dining areas (P=0.2). No effect was found on other symptoms of illness. Provision of nutritionally balanced school meals did not affect school attendance, asthma, allergies, illness or well-being in 8- to 11-year-old children. The slight increase in occurrence of headaches seems to be related to the physical eating environment.

[The exercise training restores the heart rate variability in heart failure patients. A systematic review].

PubMed

Segovia, Victoria; Manterola, Carlos; González, Marcelo; Rodríguez-Núñez, Iván

Cardiovascular diseases are a significant cause of morbidity and mortality in the general population. In this sense, the autonomic imbalance is the cornerstone of the pathophysiology underlying the development of these diseases. The aim of this study was to determine the efficacy of exercise training on heart rate variability (HRV) in adult patients with chronic heart failure. A systematic literature review was conducted in electronic databases. The considered studies were randomised clinical trials, quasi-experimental studies with non-randomised control group, quasi-experimental studies with analysis of pre- and post- intervention, and crossover studies with randomly assigned training and non-training periods. The standardised mean differences were calculated between pre- and post-intervention in both the control and experimental group. Within-subject analysis of the control group showed no statistical significance in the standardised mean differences of HRV. In the experimental group, the standardised mean differences were positive for the root mean square of successive difference (+0.468±0.215; P=.032), high frequency band (HF) (0.934±0.256; P < .001) and low frequency band (LF) (< 0.415±0.096; P=.001). Moreover, the standardised mean difference was negative for LF/HF (-0.747±0.369, P=<.044). On the other hand, only 3 studies entered the comparative meta-analysis. The effect of exercise training was favourable for the experimental group in LF/HF (-2.21±95% CI: -3.83 to -0.60), HF, and LF. The exercise training was effective in increasing HRV and restoring the autonomic balance in patients with heart failure. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome.

PubMed

Lund, P; Sangild, P T; Aunsholt, L; Hartmann, B; Holst, J J; Mortensen, J; Mortensen, P B; Jeppesen, P B

2012-09-01

Colostrum is rich in immunoregulatory, antimicrobial and trophic components supporting intestinal development and function in newborns. We assessed whether bovine colostrum could enhance intestinal adaptation and function in adult short bowel syndrome (SBS) patients. Twelve SBS patients in this randomised cross-over study received 4 weeks oral supplement of bovine colostrum or an iso-energetic and iso-proteinaceous control (2.4 MJ/d, 500 ml/day) separated by a 4-week washout period. Patients were admitted four times for 72-h periods of fluid, electrolyte and nutrient balance studies. Meals, faeces and urine were weighed, and energy, macronutrient and electrolyte contents were analysed to calculate net nutrient uptake. Body composition was measured by dual-energy X-ray absorptiometry scans, and functional tests of handgrip strength and lung functions were performed. Eight patients completed the study and were included in the analysis. Both supplements (colostrum and control) not only increased protein (0.96 ± 0.42 MJ/d, P=0.004 1.03 ± 0.44 MJ/d, P=0.003) and energy (1.46 ± 1.02 MJ/d, P=0.005, 1.76 ± 1.46 MJ/d, P=0.01) absorption but also absolute faecal wet weight excretions (231 ± 248 g/d, P=0.002, 319 ± 299 g/d, P=0.03), compared with baseline measurements. Both supplements improved handgrip strength (P=0.03) while only the control supplement increased lean body mass (1.12 ± 1.33 kg, P<0.049). Colostrum was not found to be superior to the control. Intake of high-protein milk supplements increased net nutrient absorption for adult SBS patients, but at the expense of increased diarrhoea. Despite high contents of bioactive factors, colostrum did not significantly improve intestinal absorption, body composition or functional tests compared with the control.

Evaluation of personalised, one-to-one interaction using Montessori-type activities as a treatment of challenging behaviours in people with dementia: the study protocol of a crossover trial.

PubMed

van der Ploeg, Eva S; O'Connor, Daniel W

2010-01-24

The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out) are stressful to both nursing home residents and their carers and are difficult to treat. Behaviours stemming from pain, major depression or psychosis benefit from treatment with analgesics, antidepressants or antipsychotics. In other cases, psychotropic medications have limited efficacy but are used very widely. Therefore, increasingly more attention has been paid to nonpharmacological interventions which are associated with fewer risks. The aim of the current study is to test if personalised one-to-one interaction activities based on Montessori principles will reduce the frequency of behavioural symptoms of dementia significantly more than a relevant control condition. We will conduct a controlled trial with randomised cross-over between conditions. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to Montessori or control blocks for two weeks then switched to the other condition. Montessori activities derive from the principles espoused by Maria Montessori and subsequent educational theorists to promote engagement in learning, namely task breakdown, guided repetition, progression in difficulty from simple to complex, and the careful matching of demands to levels of competence. The control intervention consists of conversation or reading from and looking at pictures in a newspaper to control for non-specific benefits of one-to-one interaction. Presence of target behaviour will be noted as well as level of engagement and type of affect displayed. Secondary measures also include the Cohen-Mansfield Agitation Inventory and information on time and funds spend to prepare the activities. If our results show that use of Montessori activities is effective in treating challenging behaviours in individuals with dementia, it will potentially provide a safer and more enjoyable intervention rather than reliance on pharmacology alone. Australian New Zealand Clinical Trials Registry - ACTRN12609000564257.

No effects of 20 Hz-rTMS of the primary motor cortex in vegetative state: A randomised, sham-controlled study.

PubMed

Cincotta, Massimo; Giovannelli, Fabio; Chiaramonti, Roberta; Bianco, Giovanni; Godone, Marco; Battista, Donato; Cardinali, Consuelo; Borgheresi, Alessandra; Sighinolfi, Antonella; D'Avanzo, Anna Maria; Breschi, Marco; Dine, Ylli; Lino, Mario; Zaccara, Gaetano; Viggiano, Maria Pia; Rossi, Simone

2015-10-01

We assessed the effects of a non-invasive neuromodulatory intervention with repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with vegetative state (VS) by a randomised, sham-controlled study with a cross-over design. Eleven patients classified as being in VS (9 post-anoxic, 2 post-traumatic, time elapsed from the injury 9-85 months) were included in the study. Real or sham 20 Hz rTMS were applied to the left primary motor cortex (M1) for 5 consecutive days. Primary outcome measures were changes in the JFK Coma Recovery Scale-Revised (CRS-R) scale total score and Clinical Global Impression Improvement (CGI-I) scale. Additional measures were EEG changes and impression of the patients' relatives using the CGI-I scale. Evaluations were blindly performed at baseline, after the first day of treatment, immediately after the end of the 5-days treatment, 1 week and 1 month later. Slight changes observed in the CRS-R and CGI-I scores did not significantly differ between real or sham stimulation conditions. EEG was not significantly changed on average, although spots of brain reactivity were occasionally found underneath the stimulation point. Findings did not provide evidence of therapeutic effect of 20 Hz rTMS of the M1 in chronic VS, at least with conventional coils and current safety parameters. Therefore, they might be useful to better allocate human and financial resources in future trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique.

PubMed

Parkinson, Bonny; Pearson, Sallie-Anne; Viney, Rosalie

2014-01-01

Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs). This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions. A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator. Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective. There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.

Evaluation of the injection pain with the use of DentalVibe injection system during supraperiosteal anaesthesia in children: a randomised clinical trial.

PubMed

Şermet Elbay, Ülkü; Elbay, Mesut; Yıldırım, Sİnem; Kaya, Emİne; Kaya, Can; Uğurluel, Ceren; Baydemİr, Canan

2016-09-01

The purpose of this study was to compare the use of a traditional syringe (TS) and the DentalVibe (DV) Injection Comfort System on the pain of needle insertion and injection of supraperiosteal (SP) anaesthesia into the mandibles and maxillas of children aged 6-12 years. The study was a randomised, controlled, crossover clinical trial, comprising 60 children requiring an operative procedure with SP anaesthesia on both their mandibular and maxillary molars, bilaterally. One of the molars was treated with a TS, and the contralateral tooth was treated with the DV for both arches. On each visit, subjective and objective pain was evaluated using the Wong-Baker FACES Pain Rating Scale and the Face, Leg, Activity, Cry, Consolability Scale. Patients were asked which technique they preferred. The data were analysed using Wilcoxon signed-rank test, Spearman's correlation test, and Mann-Whitney U-test. No statistically significant differences were noted between TS and DV for pain during injection and needle insertion for supraperiosteal anaesthesia in either the maxillary and mandibular operative procedures. Children experienced similar pain during SP anaesthesia administered with a TS and the DV, regardless of gender and jaw differences. DV was less preferred over the traditional procedure in children. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Does oral alprazolam affect ventilation? A randomised, double-blind, placebo-controlled trial.

PubMed

Carraro, G E; Russi, E W; Buechi, S; Bloch, Konrad E

2009-05-01

The respiratory effects of benzodiazepines have been controversial. This investigation aimed to study the effects of oral alprazolam on ventilation. In a randomised, double-blind cross-over protocol, 20 healthy men ingested 1 mg of alprazolam or placebo in random order, 1 week apart. Ventilation was unobtrusively monitored by inductance plethysmography along with end-tidal PCO(2) and pulse oximetry 60-160 min after drug intake. Subjects were encouraged to keep their eyes open. Mean +/- SD minute ventilation 120 min after alprazolam and placebo was similar (6.21 +/- 0.71 vs 6.41 +/- 1.12 L/min, P = NS). End-tidal PCO(2) and oxygen saturation did also not differ between treatments. However, coefficients of variation of minute ventilation after alprazolam exceeded those after placebo (43 +/- 23% vs 31 +/- 13%, P < 0.05). More encouragements to keep the eyes open were required after alprazolam than after placebo (5.2 +/- 5.7 vs 1.3 +/- 2.3 calls, P < 0.05). In a multiple regression analysis, higher coefficients of variation of minute ventilation after alprazolam were related to a greater number of calls. Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men. The increased variability of ventilation on alprazolam seems related to vigilance fluctuations rather than to a direct drug effect on ventilation.

Verbal working memory-related functional connectivity alterations in boys with attention-deficit/hyperactivity disorder and the effects of methylphenidate.

PubMed

Wu, Zhao-Min; Bralten, Janita; An, Li; Cao, Qing-Jiu; Cao, Xiao-Hua; Sun, Li; Liu, Lu; Yang, Li; Mennes, Maarten; Zang, Yu-Feng; Franke, Barbara; Hoogman, Martine; Wang, Yu-Feng

2017-08-01

Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH). Twenty-two boys with ADHD were scanned twice, under either MPH (single dose, 10 mg) or placebo, in a randomised, cross-over, counterbalanced placebo-controlled design. Thirty healthy boys were scanned once. We used fMRI during a numerical n-back task to examine functional connectivity patterns in case-control and MPH-placebo comparisons, using independent component analysis. There was no significant difference in behavioural performance between children with ADHD, treated with MPH or placebo, and healthy controls. Compared with controls, participants with ADHD under placebo showed increased functional connectivity within fronto-parietal and auditory networks, and decreased functional connectivity within the executive control network. MPH normalized the altered functional connectivity pattern and significantly enhanced functional connectivity within the executive control network, though in non-overlapping areas. Our study contributes to the identification of the neural substrates of working memory. Single dose of MPH normalized the altered brain functional connectivity network, but had no enhancing effect on (non-impaired) behavioural performance.

Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial.

PubMed

Diéras, Véronique; Miles, David; Verma, Sunil; Pegram, Mark; Welslau, Manfred; Baselga, José; Krop, Ian E; Blackwell, Kim; Hoersch, Silke; Xu, Jin; Green, Marjorie; Gianni, Luca

2017-06-01

The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m 2 self-administered orally twice daily on days 1-14 on each 21-day cycle, plus lapatinib 1250 mg orally once daily on days 1-21). Randomisation was stratified by world region (USA vs western Europe vs or other), number of previous chemotherapy regimens for unresectable, locally advanced, or metastatic disease (0 or 1 vs >1), and disease involvement (visceral vs non-visceral). The coprimary efficacy endpoints were progression-free survival (per independent review committee assessment) and overall survival. Efficacy was analysed in the intention-to-treat population; safety was analysed in all patients who received at least one dose of study treatment, with patients analysed according to the treatment actually received. On May 30, 2012, the study protocol was amended to allow crossover from control to trastuzumab emtansine after the second interim overall survival analysis crossed the prespecified overall survival efficacy boundary. This study is registered with ClinicalTrials.gov, number NCT00829166. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]). This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial.

PubMed

Lockyer, Stacey; Rowland, Ian; Spencer, Jeremy Paul Edward; Yaqoob, Parveen; Stonehouse, Welma

2017-06-01

Dietary polyphenols have been demonstrated to favourably modify a number of cardiovascular risk markers such as blood pressure (BP), endothelial function and plasma lipids. We conducted a randomised, double-blind, controlled, crossover trial to investigate the effects of a phenolic-rich olive leaf extract (OLE) on BP and a number of associated vascular and metabolic measures. A total of 60 pre-hypertensive [systolic blood pressure (SBP): 121-140 mmHg; diastolic blood pressure (DBP): 81-90 mmHg] males [mean age 45 (±SD 12.7 years, BMI 26.7 (±3.21) kg/m 2 ] consumed either OLE (136 mg oleuropein; 6 mg hydroxytyrosol) or a polyphenol-free control daily for 6 weeks before switching to the alternate arm after a 4-week washout. Daytime [-3.95 (±SD 11.48) mmHg, p = 0.027] and 24-h SBP [-3.33 (±SD 10.81) mmHg, p = 0.045] and daytime and 24-h DBP [-3.00 (±SD 8.54) mmHg, p = 0.025; -2.42 (±SD 7.61) mmHg, p = 0.039] were all significantly lower following OLE intake, relative to the control. Reductions in plasma total cholesterol [-0.32 (±SD 0.70) mmol/L, p = 0.002], LDL cholesterol [-0.19 (±SD 0.56) mmol/L, p = 0.017] and triglycerides [-0.18 (±SD 0.48), p = 0.008] were also induced by OLE compared to control, whilst a reduction in interleukin-8 [-0.63 (±SD 1.13) pg/ml; p = 0.026] was also detected. Other markers of inflammation, vascular function and glucose metabolism were not affected. Our data support previous research, suggesting that OLE intake engenders hypotensive and lipid-lowering effects in vivo.

Auditory integration training and other sound therapies for autism spectrum disorders: a systematic review

PubMed Central

Sinha, Y; Silove, N; Wheeler, D; Williams, K

2006-01-01

Objectives To determine the effectiveness of auditory integration training (AIT) or other methods of sound therapy in people with autism spectrum disorders (ASD). Study design A systematic review was carried out of randomised controlled trials (RCTs) of adults or children with ASD. Meta‐analysis was attempted. Results Six RCTs of AIT, including one crossover trial, were identified, with a total of 171 participants aged 3–39 years. 17 different outcome measures were used, with only two outcome measures used by three or more studies. Meta‐analysis was not possible owing to very high heterogeneity or presentation of data in unusable forms. Three studies did not show any benefit of AIT over control conditions. Three studies reported improvements at 3 months in the AIT group for total mean scores of the Aberrant Behaviour Checklist (ABC), which is of questionable validity. Of these, one study also reported improvements at 3 months in the AIT group for ABC subgroup scores. No significant adverse effects of AIT were reported. Conclusion At present there is not sufficient evidence to support its use. PMID:16887860

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

PubMed Central

Gray, Stephen

2017-01-01

Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation. PMID:27648641

A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification

PubMed Central

Garaiova, Iveta; Guschina, Irina A; Plummer, Sue F; Tang, James; Wang, Duolao; Plummer, Nigel T

2007-01-01

Background The health benefits of increased intakes of omega-3 fatty acids are well established but palatability often presents a problem. The process of emulsification is used in the food industry to provide a wider spectrum of use, often with the result of increased consumption. Moreover, as emulsification is an important step in the digestion and absorption of fats, the pre-emulsification process may enhance digestion and absorption. In this study the levels of plasma fatty acid and triacylglycerol (TAG) following the ingestion of either an oil mixture or an emulsified oil mixture have been compared. Methods In this randomised cross-over study, 13 volunteers received the oil mixture and 11 received the oil emulsion as part of an otherwise fat free meal. Blood samples were collected at 0, 1.5, 3, 4.5, 6, 7.5 and 9 hours after ingestion of oil, separated and stored at -20°C. Plasma triacylglycerols were assessed spectrophotometrically and fatty acids were determined by gas chromatography. Following a washout period of twenty days the procedure was repeated with the assignments reversed. Results The postprandial plasma TAG and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels for the emulsified oil group were increased significantly (P = 0.0182; P = 0.0493; P = 0.0137; P < 0.0001; P = 0.0355 respectively) compared with the non-emulsified oil group. The C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not significantly different for the oil and emulsified oil groups. Conclusion Pre-emulsification of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not affect absorption of shorter chain less saturated fatty acids, suggesting that pre-emulsification of fish oils may be a useful means of boosting absorption of these beneficial fatty acids. Trial registration: Current Controlled Trials ISRCTN43202606 PMID:17254329

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

PubMed

Somaraju, Usha Rani; Solis-Moya, Arturo

2014-10-13

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 14 August 2014.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 12 May 2014. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 11 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 426 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67, P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, abdominal pain and fecal fat excretion. Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency. There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial.

PubMed

Farr, Olivia M; Sofopoulos, Michail; Tsoukas, Michael A; Dincer, Fadime; Thakkar, Bindiya; Sahin-Efe, Ayse; Filippaios, Andreas; Bowers, Jennifer; Srnka, Alexandra; Gavrieli, Anna; Ko, Byung-Joon; Liakou, Chrysoula; Kanyuch, Nickole; Tseleni-Balafouta, Sofia; Mantzoros, Christos S

2016-05-01

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrolment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (functional MRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide -0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. ClinicalTrials.gov NCT01562678 FUNDING : The study was funded by Novo Nordisk, NIH UL1 RR025758 and 5T32HD052961.

Effects of subacute ingestion of chlorogenic acids on sleep architecture and energy metabolism through activity of the autonomic nervous system: a randomised, placebo-controlled, double-blinded cross-over trial.

PubMed

Park, Insung; Ochiai, Ryuji; Ogata, Hitomi; Kayaba, Momoko; Hari, Sayaka; Hibi, Masanobu; Katsuragi, Yoshihisa; Satoh, Makoto; Tokuyama, Kumpei

2017-04-01

Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous consumption of CGA reduces body fat and body weight. Since energy metabolism and sleep are controlled by common regulatory factors, consumption of CGA might modulate sleep. Lack of sleep has been identified as a risk factor for obesity, hypertension and type 2 diabetes. The aim of this study was to determine the effects of ingesting CGA over 5 d on energy metabolism and sleep quality in humans. A total of nine healthy subjects (four male and five female) completed a placebo-controlled, double-blinded, cross-over intervention study. Subjects consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth night, subjects stayed in a whole-room metabolic chamber to measure energy metabolism; sleep was evaluated using polysomnographic recording. It was found that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0·05) compared with the control, whereas no effect on sleep architecture, such as slow-wave sleep, rapid eye movement or waking after sleep onset, was observed. Indirect calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem 84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h), P<0·05) but did not affect energy expenditure during sleep. Consumption of CGA enhanced parasympathetic activity assessed from heart-rate variability during sleep (999 (sem 77) v. 919 (sem 54), P<0·05). A period of 5-d CGA consumption significantly increased fat oxidation during sleep, suggesting that beverages containing CGA may be beneficial to reduce body fat and prevent obesity. Consumption of CGA shortened sleep latency and did not adversely affect sleep quality.

Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

PubMed

Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio

2012-06-01

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

Impact of treatment crossovers on clinical outcomes in the rate and rhythm control strategies for atrial fibrillation: Insights from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial.

PubMed

Maan, Abhishek; Zhang, Zheng; Qin, Ziling; Wang, Yanbing; Dudley, Samuel; Dabhadakar, Kaustubh; Refaat, Marwan; Mansour, Moussa; Ruskin, Jeremy N; Heist, E Kevin

2017-07-01

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control. © 2017 Wiley Periodicals, Inc.

The effects of foot and facial massage on sleep induction, blood pressure, pulse and respiratory rate: crossover pilot study.

PubMed

Ejindu, Anna

2007-11-01

The study aimed to compare the effects of facial massage with that of foot massage on sleep induction and vital signs of healthy adults and to test a methodology that could be used by a lone researcher in such a study. A randomised within-group crossover pilot study of six healthy female volunteers was conducted. The interventions were a 20min foot and a 20min facial massage using peach-kernel base oil Prunus persica. A drop in systolic blood pressure of 8.5mmHg was recorded immediately after facial massage compared to that of 1mmHg recorded after foot massage. Both treatments were equally effective in reducing subjective levels of alertness during the interventions, with face massage marginally better at producing subjective sleepiness. A lone researcher using these methods would be able objectively to measure vital signs before and after interventions, but not during; and would be able subjectively to measure sleep induction in non-sleep-laboratory contexts.

Sport stacking in auditory and visual attention of grade 3 learners.

PubMed

Mortimer, J; Krysztofiak, J; Custard, S; McKune, A J

2011-08-01

The effect of sport stacking on auditory and visual attention in 32 Grade 3 children was examined using a randomised, cross-over design. Children were randomly assigned to a sport stacking (n=16) or arts/crafts group (n=16) with these activities performed over 3 wk. (12 30-min. sessions, 4 per week). This was followed by a 3-wk. wash-out period after which there was a cross-over and the 3-wk. intervention repeated, with the sports stacking group performing arts/crafts and the arts/crafts group performing sports stacking. Performance on the Integrated Visual and Auditory Continuous Performance Test, a measure of auditory and visual attention, was assessed before and after each of the 3-wk. interventions for each group. Comparisons indicated that sport stacking resulted in significant improvement in high demand function and fine motor regulation, while it caused a significant reduction in low demand function. Auditory and visual attention adaptations to sport stacking may be specific to the high demand nature of the task.

Consumption of a diet rich in Brassica vegetables is associated with a reduced abundance of sulphate-reducing bacteria: A randomised crossover study.

PubMed

Kellingray, Lee; Tapp, Henri S; Saha, Shikha; Doleman, Joanne F; Narbad, Arjan; Mithen, Richard F

2017-09-01

We examined whether a Brassica-rich diet was associated with an increase in the relative abundance of intestinal lactobacilli and sulphate-reducing bacteria (SRB), or alteration to the composition of the gut microbiota, in healthy adults. A randomised crossover study was performed with ten healthy adults who were fed a high- and a low-Brassica diet for 2-wk periods, with a 2-wk washout phase separating the diets. The high-Brassica diet consisted of six 84 g portions of broccoli, six 84 g portions of cauliflower and six 300 g portions of a broccoli and sweet potato soup. The low-Brassica diet consisted of one 84 g portion of broccoli and one 84 g portion of cauliflower. Faecal microbiota composition was measured in samples collected following 2-wk Brassica-free periods (consumption of all Brassica prohibited), and after each diet, whereby the only Brassica consumed was that supplied by the study team. No significant changes to the relative abundance of lactobacilli were observed (p = 0.8019). The increased consumption of Brassica was associated with a reduction in the relative abundance of SRB (p = 0.0215), and members of the Rikenellaceae, Ruminococcaceae, Mogibacteriaceae, Clostridium and unclassified Clostridiales (p < 0.01). The increased consumption of Brassica vegetables was linked to a reduced relative abundance of SRB, and therefore may be potentially beneficial to gastrointestinal health. © 2017 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A busy day has minimal effect on factors associated with falls in older people: An ecological randomised crossover trial.

PubMed

Sturnieks, Daina L; Yak, Sin Lin; Ratanapongleka, Mayna; Lord, Stephen R; Menant, Jasmine C

2018-06-01

Fatigue is a common complaint in older people. Laboratory-induced muscle fatigue has been found to affect physical functions in older populations but these protocols are rigorous and are unlikely to accurately reflect daily activities. This study used an ecological approach to determine the effects of a busy day on self-reported fatigue and fall-related measures of physical and cognitive function in older people. Fifty community-dwelling adult volunteers, aged 60-88 (mean 73) years participated in this randomised crossover trial. Participants undertook assessments of balance, strength, gait, mobility, cognitive function and self-reported fatigue, before and after a planned rest day and a planned busy day (randomly allocated) at least one week apart. Participants wore an activity monitor on both the rest and busy days. On average, participants undertook twice as many steps and 2.5 times more minutes of activity on the busy, compared with the rest day. Participants had a significant increase in self-reported fatigue on the afternoon of the busy day and no change on the rest day. Repeated measures ANOVAs found no significant day (rest/busy) × time (am/pm) interaction effects, except for the timed up and go test of mobility, resulting from relatively improved mobility performance over the rest day, compared with the busy day. This study showed few effects of a busy day on physical and cognitive performance tests associated with falls in older people. Copyright © 2018 Elsevier Inc. All rights reserved.

Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF)--what is the difference?

PubMed

Höglund, M

1998-12-01

Two forms of recombinant human G-CSF (rhG-CSF) are available for clinical use: filgrastim is expressed in E coli and non-glycosylated, whereas lenograstim is derived from Chinese hamster ovary (CHO) cells and glycosylated. The function of the sugar chain, accounting for approximately 4% of the molecular weight of lenograstim (and native G-CSF), is not known. Glycosylation of the G-CSF molecule does not prolong its circulation half life. Lenograstim is more active than filgrastim (and research-use deglycosylated G-CSF) on a weight-by-weight basis in in vitro colony-forming and cell line assays. An international potency standard assigns a specific activity of 100,000 IU/microgram to filgrastim and 127,760 IU/microgram to lenograstim. Correspondingly, two randomised crossover studies in normal subjects, comparing mass equivalent doses of the two rhG-CSFs, have demonstrated a 25-30% higher concentration of blood stem cells (CD34+, CFU-GM) during lenograstim administration. No difference in side effects was observed. Results from a prospective, randomised, non-crossover trial in breast cancer patients suggest that bioequivalent doses of filgrastim and lenograstim have a similar effect on mobilisation of CD34+ cells and immature CD34+ cell subsets, respectively. Although comparisons outside the setting of stem cell mobilisation are lacking, the clinical relevance of the greater specific activity of lenograstim may thus be limited. The difference in potency between microgram identical doses of the two rhG-CSFs makes dosing in biological units (IU) rather than mass units (microgram) more appropriate.

Impact of High-Intensity-NIV on the heart in stable COPD: a randomised cross-over pilot study.

PubMed

Duiverman, Marieke Leontine; Maagh, Petra; Magnet, Friederike Sophie; Schmoor, Claudia; Arellano-Maric, Maria Paola; Meissner, Axel; Storre, Jan Hendrik; Wijkstra, Peter Jan; Windisch, Wolfram; Callegari, Jens

2017-05-02

Although high-intensity non-invasive ventilation has been shown to improve outcomes in stable COPD, it may adversely affect cardiac performance. Therefore, the aims of the present pilot study were to compare cardiac and pulmonary effects of 6 weeks of low-intensity non-invasive ventilation and 6 weeks of high-intensity non-invasive ventilation in stable COPD patients. In a randomised crossover pilot feasibility study, the change in cardiac output after 6 weeks of each NIV mode compared to baseline was assessed with echocardiography in 14 severe stable COPD patients. Furthermore, CO during NIV, gas exchange, lung function, and health-related quality of life were investigated. Three patients dropped out: two deteriorated on low-intensity non-invasive ventilation, and one presented with decompensated heart failure while on high-intensity non-invasive ventilation. Eleven patients were included in the analysis. In general, cardiac output and NTproBNP did not change, although individual effects were noticed, depending on the pressures applied and/or the co-existence of heart failure. High-intensity non-invasive ventilation tended to be more effective in improving gas exchange, but both modes improved lung function and the health-related quality of life. Long-term non-invasive ventilation with adequate pressure to improve gas exchange and health-related quality of life did not have an overall adverse effect on cardiac performance. Nevertheless, in patients with pre-existing heart failure, the application of very high inspiratory pressures might reduce cardiac output. The trial was registered in the Deutsches Register Klinischer Studien (DRKS-ID: DRKS00007977 ).

A Randomised Cross-Over Pharmacokinetic Bioavailability Study of Synthetic versus Kiwifruit-Derived Vitamin C

PubMed Central

Carr, Anitra C.; Bozonet, Stephanie M.; Vissers, Margreet C. M.

2013-01-01

Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged 18–35 years) received either a chewable tablet (200 mg vitamin C) or the equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold). Fasting blood and urine were collected half hourly to hourly over the eight hours following intervention. The ascorbate content of the plasma and urine was determined using HPLC with electrochemical detection. Plasma ascorbate levels increased from 0.5 h after the intervention (P = 0.008). No significant differences in the plasma time-concentration curves were observed between the two interventions (P = 0.645). An estimate of the total increase in plasma ascorbate indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived vitamin C. There was an increase in urinary ascorbate excretion, relative to urinary creatinine, from two hours post intervention (P < 0.001). There was also a significant difference between the two interventions, with enhanced ascorbate excretion observed in the kiwifruit group (P = 0.016). Urinary excretion was calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic vitamin C. PMID:24284610

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

PubMed

Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

2015-06-01

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study.

PubMed

Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

2007-11-01

To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Randomised, double blind, placebo controlled crossover trial, with two 2-week treatment periods separated by a 2-week placebo washout. Six UK paediatric departments. 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting > or =3 months), defined as < or =2 complete bowel movements per week and one of the following: pain on defaecation on 25% of days; > or =25% of bowel movements with straining; > or =25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; p<0.001). Further significant differences in favour of PEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (p<0.001), stool consistency (p<0.001) and percentage of hard stools (p = 0.001). Treatment related adverse events (all mild or moderate) occurred in similar numbers of children on PEG+E (41%) and placebo during treatment (45%). PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study

PubMed Central

Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

2007-01-01

Objectives To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Design Randomised, double blind, placebo controlled crossover trial, with two 2‐week treatment periods separated by a 2‐week placebo washout. Setting Six UK paediatric departments. Participants 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting ⩾3 months), defined as ⩽2 complete bowel movements per week and one of the following: pain on defaecation on 25% of days; ⩾25% of bowel movements with straining; ⩾25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Main outcome measures Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. Results The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; p<0.001). Further significant differences in favour of PEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (p<0.001), stool consistency (p<0.001) and percentage of hard stools (p = 0.001). Treatment related adverse events (all mild or moderate) occurred in similar numbers of children on PEG+E (41%) and placebo during treatment (45%). Conclusions PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children. PMID:17626140

Glucose effectiveness, but not insulin sensitivity, is improved after short-term interval training in individuals with type 2 diabetes mellitus: a controlled, randomised, crossover trial.

PubMed

Karstoft, Kristian; Clark, Margaret A; Jakobsen, Ida; Knudsen, Sine H; van Hall, Gerrit; Pedersen, Bente K; Solomon, Thomas P J

2017-12-01

The role of glucose effectiveness (S G ) in training-induced improvements in glucose metabolism in individuals with type 2 diabetes is unknown. The objectives and primary outcomes of this study were: (1) to assess the efficacy of interval walking training (IWT) and continuous walking training (CWT) on S G and insulin sensitivity (S I ) in individuals with type 2 diabetes; and (2) to assess the association of changes in S G and S I with changes in glycaemic control. Fourteen participants with type 2 diabetes underwent three trials (IWT, CWT and no training) in a crossover study. Exclusion criteria were exogenous insulin treatment, smoking, pregnancy, contraindications to structured physical activity and participation in recurrent training (>90 min/week). The trials were performed in a randomised order (computerised-generated randomisation). IWT and CWT consisted of ten supervised treadmill walking sessions, each lasting 60 min, over 2 weeks. IWT was performed as repeated cycles of 3 min slow walking and 3 min fast walking (aiming for 54% and 89% of [Formula: see text], respectively, which was measured during the last minute of each interval), and CWT was performed aiming for a moderate walking speed (73% of [Formula: see text]). A two-step (pancreatic and hyperinsulinaemic) hyperglycaemic clamp was implemented before and after each trial. All data were collected in a hospitalised setting. Neither participants nor assessors were blinded to the trial interventions. Thirteen individuals completed all procedures and were included in the analyses. IWT improved S G (mean ± SEM: 0.6 ± 0.1 mg kg -1  min -1 , p < 0.05) but not S I (p > 0.05), whereas CWT matched for energy expenditure and time duration improved neither S G nor S I (both p > 0.05). Changes in S G , but not in S I , were associated with changes in mean (β = -0.62 ± 0.23, r 2  = 0.17, p < 0.01) and maximum (β = -1.18 ± 0.52, r 2  = 0.12, p < 0.05) glucose levels during 24 h continuous glucose monitoring. Two weeks of IWT, but not CWT, improves S G but not S I in individuals with type 2 diabetes. Moreover, changes in S G are associated with changes in glycaemic control. Therefore, increased S G is likely an important mechanism by which training improves glycaemic control in individuals with type 2 diabetes. ClinicalTrials.gov NCT02320526 FUNDING: CFAS is supported by a grant from TrygFonden. During the study period, the Centre of Inflammation and Metabolism (CIM) was supported by a grant from the Danish National Research Foundation (DNRF55). The study was further supported by grants from Diabetesforeningen, Augustinusfonden and Krista og Viggo Petersens Fond. CIM/CFAS is a member of DD2-the Danish Center for Strategic Research in Type 2 Diabetes (the Danish Council for Strategic Research, grant no. 09-067009 and 09-075724).

Combined caffeine and bright light reduces dangerous driving in sleep-deprived healthy volunteers: a pilot cross-over randomised controlled trial.

PubMed

Hartley, S L; Barbot, F; Machou, M; Lejaille, M; Moreau, B; Vaugier, I; Lofaso, F; Quera-Salva, M A

2013-06-01

To explore the effects of caffeine and bright light therapy on simulated nighttime driving in sleep-deprived healthy volunteers. Twelve male healthy volunteers aged 20 to 50 years participated in a randomized cross-over study of simulated nighttime driving at a sleep laboratory, followed by recovery sleep with polysomnography at home. The volunteers received variable combinations of caffeine 200mg (C+), caffeine placebo (C-), bright light 10,000 lux (L+), and bright light placebo<50 lux (L-), in four sessions (C+L+, C+L-, C-L+, C-L-), in random order with a wash-out period of 7 days. Treatments were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and 6 a.m. Lane drifting was the primary outcome measure. Other measures were reaction times, self-rated fatigue, sleepiness and recovery sleep. Without treatment, lane drifting increased throughout the night, and objective and subjective vigilance declined. Paired comparisons showed that lane drifting was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a global treatment effect on lane drifting. Lane drifting at 6 a.m. was significantly decreased with C+L+ compared to C-L-. Bright light therapy combined with caffeine administered at 1 a.m. decreased lane drifting by healthy volunteers during simulated nighttime driving. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption.

PubMed

Tuck, C J; Ross, L A; Gibson, P R; Barrett, J S; Muir, J G

2017-02-01

In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h -1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders. © 2016 The British Dietetic Association Ltd.

Milk minerals modify the effect of fat intake on serum lipid profile: results from an animal and a human short-term study.

PubMed

Lorenzen, Janne K; Jensen, Søren K; Astrup, Arne

2014-04-28

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid profile. We present data from two studies. Study I had a randomised, blinded, parallel design (n 24 pigs) with a 10 d adaptation period during which a high-fat diet was fed to the pigs and a 14 d intervention period during which the same diet either enriched with milk minerals (MM group) or placebo (control group) was fed to the pigs. Study II had a randomised cross-over design (n 9 men) where the subjects were fed either a high-fat diet enriched with milk minerals (MM period) or a regular diet (control period). In both the studies, blood variables were measured before and after the intervention and faecal and urine samples were collected at the end of the dietary periods. The increase in plasma total cholesterol and LDL-cholesterol concentrations but not in HDL-cholesterol concentration was markedly lowered by milk minerals in both the studies. In the animal study, baseline adjusted total cholesterol and LDL-cholesterol concentrations in the MM group were 11% (P = 0.004) and 13% (P = 0.03) lower compared with those in the control group after the intervention. Similarly in the human study, baseline adjusted total cholesterol and LDL-cholesterol concentrations were 6% (P = 0.002) and 9% (P = 0.03) lower after the MM period compared with those in the control period. HDL-cholesterol concentration was not lowered by milk minerals. These short-term studies indicate that the addition of milk minerals to a high-fat diet to some extent attenuates the increase in total cholesterol and LDL-cholesterol concentrations, without affecting HDL-cholesterol concentration.

Cluster randomised crossover trials with binary data and unbalanced cluster sizes: application to studies of near-universal interventions in intensive care.

PubMed

Forbes, Andrew B; Akram, Muhammad; Pilcher, David; Cooper, Jamie; Bellomo, Rinaldo

2015-02-01

Cluster randomised crossover trials have been utilised in recent years in the health and social sciences. Methods for analysis have been proposed; however, for binary outcomes, these have received little assessment of their appropriateness. In addition, methods for determination of sample size are currently limited to balanced cluster sizes both between clusters and between periods within clusters. This article aims to extend this work to unbalanced situations and to evaluate the properties of a variety of methods for analysis of binary data, with a particular focus on the setting of potential trials of near-universal interventions in intensive care to reduce in-hospital mortality. We derive a formula for sample size estimation for unbalanced cluster sizes, and apply it to the intensive care setting to demonstrate the utility of the cluster crossover design. We conduct a numerical simulation of the design in the intensive care setting and for more general configurations, and we assess the performance of three cluster summary estimators and an individual-data estimator based on binomial-identity-link regression. For settings similar to the intensive care scenario involving large cluster sizes and small intra-cluster correlations, the sample size formulae developed and analysis methods investigated are found to be appropriate, with the unweighted cluster summary method performing well relative to the more optimal but more complex inverse-variance weighted method. More generally, we find that the unweighted and cluster-size-weighted summary methods perform well, with the relative efficiency of each largely determined systematically from the study design parameters. Performance of individual-data regression is adequate with small cluster sizes but becomes inefficient for large, unbalanced cluster sizes. When outcome prevalences are 6% or less and the within-cluster-within-period correlation is 0.05 or larger, all methods display sub-nominal confidence interval coverage, with the less prevalent the outcome the worse the coverage. As with all simulation studies, conclusions are limited to the configurations studied. We confined attention to detecting intervention effects on an absolute risk scale using marginal models and did not explore properties of binary random effects models. Cluster crossover designs with binary outcomes can be analysed using simple cluster summary methods, and sample size in unbalanced cluster size settings can be determined using relatively straightforward formulae. However, caution needs to be applied in situations with low prevalence outcomes and moderate to high intra-cluster correlations. © The Author(s) 2014.

Acute ingestion of different macronutrients differentially enhances aspects of memory and attention in healthy young adults.

PubMed

Jones, Emma K; Sünram-Lea, Sandra I; Wesnes, Keith A

2012-02-01

The role of carbohydrates on mood and cognition is fairly well established, however research examining the behavioural effects of the other macronutrients is limited. The current study compared the effects of a 25 g glucose drink to energetically matched protein and fat drinks and an inert placebo. Following a blind, placebo-controlled, randomised crossover design, 18 healthy young adults consumed drinks containing fat, glucose, protein and placebo. Cognitive performance was examined at baseline and again 15- and 60 min post drink. Mood was assessed at baseline and then 10-, 35- and 80 min post drink. Attention and speed were enhanced 15 min following fat or glucose ingestion and working memory was enhanced 15 min following protein ingestion. Sixty minutes post drink memory enhancements were observed after protein and memory impairment was observed following glucose. All drinks increased ratings of alertness. The findings suggest that macronutrients: (i) have different windows of opportunity for effects (ii) target different cognitive domains. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of cereal bar containing polydextrose on subjective feelings of appetite and energy intake in overweight adults over 15 d.

PubMed

Martinelli, Marcela; Hick, Emilia; Walz, Florencia; Drago, Silvina R

2018-01-18

The effects of 15 d polydextrose (16.7 g) consumption on energy intake (EI) and appetite feelings were investigated. Overweight adults consumed a polydextrose-bar or a control-bar matched in energy content as a midmorning snack for 15 consecutive days in a single-blind, randomised, crossover design. The two 15-d intervention periods were separated by a 15-d washout period. On the day 1 and the day 15 of each intervention period, energy intake (primary outcome) and appetite feelings (secondary outcome) were assessed. There were not significant main effects of the day, type of bar, or their interaction for EI (at lunchtime test meal, at rest of the day, or at total daily) or subjective feelings (hunger, desire to eat, fullness, and prospective food consumption) during the satiation and satiety periods. The results showed the consumption of polydextrose-bar during 15 d did not significantly affect energy intake and subjective feelings of appetite in overweight adults.

Controlled trial of Iodosorb in chronic venous ulcers.

PubMed Central

Ormiston, M C; Seymour, M T; Venn, G E; Cohen, R I; Fox, J A

1985-01-01

Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly. PMID:3926169

Vitamin K supplementation for cystic fibrosis.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

2011-01-19

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 April 2010. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Vitamin K supplementation for cystic fibrosis.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

2013-04-30

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 11 October 2012. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

A randomised crossover trial of the acute effects of a deep-fried Mars bar or porridge on the cerebral vasculature.

PubMed

Dunn, William G; Walters, Matthew R

2014-11-01

The deep-fried Mars bar has been cited as 'all that is wrong with the high-fat, high-sugar Scottish diet'. We investigated the effect of ingestion of a deep-fried Mars bar or porridge on cerebrovascular reactivity. We hypothesised that deep-fried Mars bar ingestion would impair cerebrovascular reactivity, which is associated with increased risk of ischaemic stroke. Twenty-four fasted volunteers were randomised to receive a deep-fried Mars bar and then porridge (control), or vice-versa. We used transcranial Doppler ultrasound to calculate Breath Holding Index as a surrogate measure of cerebrovascular reactivity. Change in Breath Holding Index post-ingestion was the primary outcome measure. Twenty-four healthy adults (mean (SD) age 21.5 (1.7) years, 14 males) completed the protocol. Deep-fried Mars bar ingestion caused a non-significant reduction in cerebrovascular reactivity relative to control (mean difference in absolute Breath Holding Index after deep-fried Mars bar versus porridge -0.11, p = 0.40). Comparison of the difference between the absolute change in Breath Holding Index between genders demonstrated a significant impairment of cerebrovascular reactivity in males (mean difference women minus men of 0.65, 95% CI 0.30 to 1.00, p = 0.0003). Ingestion of a bolus of sugar and fat caused no overall difference in cerebrovascular reactivity, but there was a modest decrease in males. Impaired cerebrovascular reactivity is associated with increased stroke risk, and therefore deep-fried Mars bar ingestion may acutely contribute to cerebral hypoperfusion in men. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Wheat bran extract alters colonic fermentation and microbial composition, but does not affect faecal water toxicity: a randomised controlled trial in healthy subjects.

PubMed

Windey, Karen; De Preter, Vicky; Huys, Geert; Broekaert, Willem F; Delcour, Jan A; Louat, Thierry; Herman, Jean; Verbeke, Kristin

2015-01-28

Wheat bran extract (WBE), containing arabinoxylan-oligosaccharides that are potential prebiotic substrates, has been shown to modify bacterial colonic fermentation in human subjects and to beneficially affect the development of colorectal cancer (CRC) in rats. However, it is unclear whether these changes in fermentation are able to reduce the risk of developing CRC in humans. The aim of the present study was to evaluate the effects of WBE on the markers of CRC risk in healthy volunteers, and to correlate these effects with colonic fermentation. A total of twenty healthy subjects were enrolled in a double-blind, cross-over, randomised, controlled trial in which the subjects ingested WBE (10 g/d) or placebo (maltodextrin, 10 g/d) for 3 weeks, separated by a 3-week washout period. At the end of each study period, colonic handling of NH3 was evaluated using the biomarker lactose[15N, 15N']ureide, colonic fermentation was characterised through a metabolomics approach, and the predominant microbial composition was analysed using denaturing gradient gel electrophoresis. As markers of CRC risk, faecal water genotoxicity was determined using the comet assay and faecal water cytotoxicity using a colorimetric cell viability assay. Intake of WBE induced a shift from urinary to faecal 15N excretion, indicating a stimulation of colonic bacterial activity and/or growth. Microbial analysis revealed a selective stimulation of Bifidobacterium adolescentis. In addition, WBE altered the colonic fermentation pattern and significantly reduced colonic protein fermentation compared with the run-in period. However, faecal water cytotoxicity and genotoxicity were not affected. Although intake of WBE clearly affected colonic fermentation and changed the composition of the microbiota, these changes were not associated with the changes in the markers of CRC risk.

An intervention for pulmonary rehabilitators to develop a social identity for patients attending exercise rehabilitation: a feasibility and pilot randomised control trial protocol.

PubMed

Levy, Andrew R; Matata, Bashir; Pilsworth, Sam; Mcgonigle, Adrian; Wigelsworth, Lyndsey; Jones, Linda; Pott, Nicola; Bettany, Max; Midgley, Adrian W

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health-related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators' practice. This study aims to pilot and feasibly explore a social identity group management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. This is a two-centre, randomised cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre- and post-exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants' contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention's effectiveness for improving HRQoL for COPD patients. ClinicalTrials.gov NCT02288039. Date 31 October 2014.

Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

PubMed

Lees, J; Michalopoulou, P G; Lewis, S W; Preston, S; Bamford, C; Collier, T; Kalpakidou, A; Wykes, T; Emsley, R; Pandina, G; Kapur, S; Drake, R J

2017-10-01

Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.

PubMed

Cross, M D; Mills, N L; Al-Abri, M; Riha, R; Vennelle, M; Mackay, T W; Newby, D E; Douglas, N J

2008-07-01

The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.

Impact of N-acetylcysteine on endothelial function, B-type natriuretic peptide and renal function in patients with the cardiorenal syndrome: a pilot cross over randomised controlled trial.

PubMed

Camuglia, Anthony C; Maeder, Micha T; Starr, Jennifer; Farrington, Catherine; Kaye, David M

2013-04-01

Both heart and renal failure are characterised by increased systemic oxidative stress and endothelial dysfunction and occur in the cardiorenal syndrome (CRS). The aim of the present study was to assess the impact of N-acetylcysteine (NAC), a potent antioxidant, on endothelial function, B-type natriuretic peptide (BNP) and renal function in patients with CRS. In a double blind, placebo controlled manner, we randomised nine stable outpatients with both heart failure (LVEF<40% and NYHA class II or III) and renal failure (Cockroft Gault clearance of 20-60ml/min) to placebo or NAC (500mg orally twice daily) for 28 days followed by a wash out period (>7 days) and crossover to the other treatment. Eight patients completed the study and all data (N=9) was used in the analysis. Mean forearm blood flow improved significantly with NAC with mean ratio of improvement of 1.99 (SEM: ±0.49) for NAC and 0.73 (SEM: ±0.23) for placebo with a p-value of 0.047. There was no significant difference in BNP (p=0.25), renal function (p=0.71) or NYHA class (p=0.5). No deaths occurred during the trial. In this pilot trial of patients with CRS, NAC therapy was associated with improved forearm blood flow. This may represent a general improvement in endothelial function and warrants further investigation of antioxidant therapy in these patients. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Postprandial effects of test meals including concentrated arabinoxylan and whole grain rye in subjects with the metabolic syndrome: a randomised study.

PubMed

Hartvigsen, M L; Lærke, H N; Overgaard, A; Holst, J J; Bach Knudsen, K E; Hermansen, K

2014-05-01

Prospective studies have shown an inverse relationship between whole grain consumption and the risk of type 2 diabetes, where short chain fatty acids (SCFA) may be involved. Our objective was to determine the effect of isolated arabinoxylan alone or in combination with whole grain rye kernels on postprandial glucose, insulin, free fatty acids (FFA), gut hormones, SCFA and appetite in subjects with the metabolic syndrome (MetS). Fifteen subjects with MetS participated in this acute, randomised, cross-over study. The test meals each providing 50 g of digestible carbohydrate were as follows: semolina porridge added concentrated arabinoxylan (AX), rye kernels (RK) or concentrated arabinoxylan combined with rye kernels (AXRK) and semolina porridge as control (SE). A standard lunch was served 4 h after the test meals. Blood samples were drawn during a 6-h period, and appetite scores and breath hydrogen were assessed every 30 min. The AXRK meal reduced the acute glucose (P=0.005) and insulin responses (P<0.001) and the feeling of hunger (P=0.005; 0-360 min) compared with the control meal. The AX and AXRK meals increased butyrate and acetate concentrations after 6 h. No significant differences were found for the second meal responses of glucose, insulin, FFA, glucagon-like peptide-1 or ghrelin. Our results indicate a stimulatory effect of arabinoxylan on butyrate and acetate production, however, with no detectable effect on the second meal glucose response. It remains to be tested in a long-term study if a beneficial effect on the glucose response of the isolated arabinoxylan will be related to the SCFA production.

Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

PubMed

Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

2016-06-01

No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

Effect of fibre additions to flatbread flour mixes on glucose kinetics: a randomised controlled trial.

PubMed

Boers, Hanny M; van Dijk, Theo H; Hiemstra, Harry; Hoogenraad, Anne-Roos; Mela, David J; Peters, Harry P F; Vonk, Roel J; Priebe, Marion G

2017-11-01

We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different 13C-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T 50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T 50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production.

Acute effect of sorghum flour-containing pasta on plasma total polyphenols, antioxidant capacity and oxidative stress markers in healthy subjects: A randomised controlled trial.

PubMed

Khan, Imran; Yousif, Adel M; Johnson, Stuart K; Gamlath, Shirani

2015-06-01

It has been previously reported that pasta containing wholegrain sorghum flour exhibits high content of polyphenols and antioxidant capacity and hence might enhance antioxidant status and reduce markers of oxidative stress in vivo; however no clinical studies have yet been reported. Therefore, the present study assessed the effect of pasta containing red or white wholegrain sorghum flour on plasma total polyphenols, antioxidant capacity and oxidative stress markers in humans. The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN: 12612000324819). In a randomised crossover design, healthy subjects (n = 20) consumed three test meals of control pasta (CP), 30% red sorghum pasta (RSP) or 30% white sorghum pasta (WSP), 1-2 wk apart. The test meals were consumed as breakfast after an overnight fast. Blood samples were obtained at fasting and 2 h after consumption and analysed for total polyphenols, antioxidant capacity, superoxide dismutase (SOD) activity, protein carbonyl and 8-isoprostanes. Compared to baseline, the 2 h post-prandial levels following the RSP meal of plasma polyphenols, antioxidant capacity and SOD activity were significantly (P < 0.001) higher while the protein carbonyl level was significantly lower (P = 0.035). Furthermore, net changes in polyphenols, antioxidant capacity and SOD activity were significantly (P < 0.001) higher while protein carbonyl were significantly (P = 0.035) lower following consumption of the RSP meal than the CP meal. The results demonstrated that pasta containing red wholegrain sorghum flour enhanced antioxidant status and improved markers of oxidative stress in healthy subjects. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Double-blind randomised controlled trial of the independent and synergistic effect of Spirulina maxima with exercise (ISESE) on general fitness, lipid profile and redox status in overweight and obese subjects: study protocol.

PubMed

Hernández-Lepe, Marco Antonio; López-Díaz, José Alberto; Rosa, Laura Alejandra de la; Hernández-Torres, Rosa Patricia; Wall-Medrano, Abraham; Juarez-Oropeza, Marco Antonio; Pedraza-Chaverri, José; Urquidez-Romero, Rene; Ramos-Jiménez, Arnulfo

2017-06-23

In order to reduce cardiovascular disease risk factors, a healthy diet must include dietary antioxidants from different sources (eg, Spirulina maxima ) and regular practice of exercise should be promoted. There is some evidence from animal studies that S. maxima and exercise decrease cardiovascular disease risks factors. However, very few studies have proved the independent or synergistic effect of S. maxima plus exercise in humans. This study attempts to address the independent and synergistic effects in overweight and obese subjects participating in a systematic physical exercise programme at moderate intensity on general fitness, plasma lipid profile and antioxidant capacity. Using a randomised, double-blind, placebo-controlled, counterbalanced crossover study design, 80 healthy overweight and obese subjects will be evaluated during a 12-week isoenergetic diet accompanied by 4.5 g/day S. maxima intake and/or a physical systematic exercise programme at moderate intensity. Body composition, oxygen uptake, heart rate, capillary blood lactate, plasma concentrations of triacylglycerols, total, low-density and high-density lipoprotein cholesterol, antioxidant status, lipid oxidation, protein carbonyls, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione reductase and paraoxonase will be assessed. This study and all the procedures have been approved by the Universidad Autonoma de Ciudad Juarez Bioethics Committee. Findings will be disseminated through peer-reviewed journals, national and international conferences. ClinicalTrials.gov: NCT02837666. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A randomised controlled trial evaluating the effect of potassium supplementation on vascular function and the renin-angiotensin-aldosterone system.

PubMed

Graham, U M; McCance, D R; Young, I S; Mullan, K R

2014-05-01

There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs. 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs. 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs. 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs. 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone.

A Case Study of Controlling Crossover in a Selection Hyper-heuristic Framework Using the Multidimensional Knapsack Problem.

PubMed

Drake, John H; Özcan, Ender; Burke, Edmund K

2016-01-01

Hyper-heuristics are high-level methodologies for solving complex problems that operate on a search space of heuristics. In a selection hyper-heuristic framework, a heuristic is chosen from an existing set of low-level heuristics and applied to the current solution to produce a new solution at each point in the search. The use of crossover low-level heuristics is possible in an increasing number of general-purpose hyper-heuristic tools such as HyFlex and Hyperion. However, little work has been undertaken to assess how best to utilise it. Since a single-point search hyper-heuristic operates on a single candidate solution, and two candidate solutions are required for crossover, a mechanism is required to control the choice of the other solution. The frameworks we propose maintain a list of potential solutions for use in crossover. We investigate the use of such lists at two conceptual levels. First, crossover is controlled at the hyper-heuristic level where no problem-specific information is required. Second, it is controlled at the problem domain level where problem-specific information is used to produce good-quality solutions to use in crossover. A number of selection hyper-heuristics are compared using these frameworks over three benchmark libraries with varying properties for an NP-hard optimisation problem: the multidimensional 0-1 knapsack problem. It is shown that allowing crossover to be managed at the domain level outperforms managing crossover at the hyper-heuristic level in this problem domain.

Advice to walk after meals is more effective for lowering postprandial glycaemia in type 2 diabetes mellitus than advice that does not specify timing: a randomised crossover study.

PubMed

Reynolds, Andrew N; Mann, Jim I; Williams, Sheila; Venn, Bernard J

2016-12-01

Regular physical activity is a cornerstone of diabetes management. We conducted a study to evaluate whether specifying the timing of walking in relation to meals enhances the benefits conferred by current physical activity guidelines. A total of 41 adults with type 2 diabetes mellitus (mean ± SD age 60 ± 9.9 years; mean diabetes duration 10 years) participated in this randomised, crossover study. Randomisation was by a computer-generated protocol. For periods of 2 weeks, advice to walk 30 min each day was compared with advice to walk for 10 min after each main meal. Both sets of advice met current physical activity guidelines for people with type 2 diabetes mellitus. Physical activity was measured by accelerometry over the full intervention, and glycaemia was measured using continuous glucose monitoring in 5 min intervals over 7 days. The primary outcome of postprandial glycaemia was assessed during the 3 h after a meal by the incremental area under the blood glucose curve (iAUC). The iAUC was significantly lower when participants walked after meals compared with on a single daily occasion (ratio of geometric means 0.88, 95% CI 0.78, 0.99). The improvement was particularly striking after the evening meal (0.78, 95% CI 0.67, 0.91) when the most carbohydrate was consumed and sedentary behaviours were highest. One participant died during the 30 day washout period between interventions, but participation in this study was not judged to contribute to this unfortunate event. The benefits relating to physical activity following meals suggest that current guidelines should be amended to specify post-meal activity, particularly when meals contain a substantial amount of carbohydrate. ACTRN12613000832774 FUNDING: : This study was supported by grants from the University of Otago and the New Zealand Artificial Limb Service. Glycated albumin reagents were provided by Asahi Kasei.

Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study

PubMed Central

Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

2017-01-01

Introduction Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. Methods and analysis The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4–7 days, followed by the other for a further 4–7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. Ethics and dissemination This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. Trial registration number ACTRN12617000251325; Pre-results. PMID:28760798

Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study.

PubMed

Hobbs, Jodie G; Ryan, Melissa K; Ritchie, Brett; Sluggett, Janet K; Sluggett, Andrew J; Ralton, Lucy; Reynolds, Karen J

2017-07-31

Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4-7 days, followed by the other for a further 4-7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. ACTRN12617000251325; 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.

Study protocol to assess the effectiveness and safety of a flexible family visitation model for delirium prevention in adult intensive care units: a cluster-randomised, crossover trial (The ICU Visits Study).

PubMed

Rosa, Regis Goulart; Falavigna, Maicon; Robinson, Caroline Cabral; da Silva, Daiana Barbosa; Kochhann, Renata; de Moura, Rafaela Moraes; Santos, Mariana Martins Siqueira; Sganzerla, Daniel; Giordani, Natalia Elis; Eugênio, Cláudia; Ribeiro, Tarissa; Cavalcanti, Alexandre Biasi; Bozza, Fernando; Azevedo, Luciano Cesar Pontes; Machado, Flávia Ribeiro; Salluh, Jorge Ibrain Figueira; Pellegrini, José Augusto Santos; Moraes, Rafael Barberena; Hochegger, Taís; Amaral, Alexandre; Teles, José Mario Meira; da Luz, Lucas Gobetti; Barbosa, Mirceli Goulart; Birriel, Daniella Cunha; Ferraz, Iris de Lima; Nobre, Vandack; Valentim, Helen Martins; Corrêa E Castro, Livia; Duarte, Péricles Almeida Delfino; Tregnago, Rogério; Barilli, Sofia Louise Santin; Brandão, Nilton; Giannini, Alberto; Teixeira, Cassiano

2018-04-13

Flexible intensive care unit (ICU) visiting hours have been proposed as a means to improve patient-centred and family-centred care. However, randomised trials evaluating the effects of flexible family visitation models (FFVMs) are scarce. This study aims to compare the effectiveness and safety of an FFVM versus a restrictive family visitation model (RFVM) on delirium prevention among ICU patients, as well as to analyse its potential effects on family members and ICU professionals. A cluster-randomised crossover trial involving adult ICU patients, family members and ICU professionals will be conducted. Forty medical-surgical Brazilian ICUs with RFVMs (<4.5 hours/day) will be randomly assigned to either an RFVM (visits according to local policies) or an FFVM (visitation during 12 consecutive hours per day) group at a 1:1 ratio. After enrolment and follow-up of 25 patients, each ICU will be switched over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome will be the cumulative incidence of delirium among ICU patients, measured twice a day using the Confusion Assessment Method for the ICU. Secondary outcome measures will include daily hazard of delirium, ventilator-free days, any ICU-acquired infections, ICU length of stay and hospital mortality among the patients; symptoms of anxiety and depression and satisfaction among the family members; and prevalence of burnout symptoms among the ICU professionals. Tertiary outcomes will include need for antipsychotic agents and/or mechanical restraints, coma-free days, unplanned loss of invasive devices and ICU-acquired pneumonia, urinary tract infection or bloodstream infection among the patients; self-perception of involvement in patient care among the family members; and satisfaction among the ICU professionals. The study protocol has been approved by the research ethics committee of all participant institutions. We aim to disseminate the findings through conferences and peer-reviewed journals. NCT02932358. © 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.

Low glycaemic index, or low glycaemic load, diets for diabetes mellitus.

PubMed

Thomas, Diana; Elliott, Elizabeth J

2009-01-21

The aim of diabetes management is to normalise blood glucose levels, since improved blood glucose control is associated with reduction in development, and progression, of complications. Nutritional factors affect blood glucose levels, however there is currently no universal approach to the optimal dietary treatment for diabetes. There is controversy about how useful the glycaemic index (GI) is in diabetic meal planning. Improved glycaemic control through diet could minimise medications, lessen risk of diabetic complications, improve quality of life and increase life expectancy. To assess the effects of low glycaemic index, or low glycaemic load, diets on glycaemic control in people with diabetes. We performed electronic searches of The Cochrane Library, MEDLINE, EMBASE and CINAHL with no language restriction. We assessed randomised controlled trials of four weeks or longer that compared a low glycaemic index, or low glycaemic load, diet with a higher glycaemic index, or load, or other diet for people with either type 1 or 2 diabetes mellitus, whose diabetes was not already optimally controlled. Two reviewers independently extracted data on study population, intervention and outcomes for each included study, using standardised data extraction forms. Eleven relevant randomised controlled trials involving 402 participants were identified. There was a significant decrease in the glycated haemoglobin A1c (HbA1c) parallel group of trials, the weighted mean difference (WMD) was -0.5% with a 95% confidence interval (CI) of - 0.9 to -0.1, P = 0.02; and in the cross-over group of trials the WMD was -0.5% with a 95% CI of -1.0 to -0.1, P = 0.03. Episodes of hypoglycaemia were significantly fewer with low compared to high GI diet in one trial (difference of -0.8 episodes per patient per month, P < 0.01), and proportion of participants reporting more than 15 hyperglycaemic episodes per month was lower for low-GI diet compared to measured carbohydrate exchange diet in another study (35% versus 66%, P = 0.006). No study reported on mortality, morbidity or costs. A low-GI diet can improve glycaemic control in diabetes without compromising hypoglycaemic events.

CUPID: a protocol of a randomised controlled trial to identify characteristics of similar Chinese patent medicines

PubMed Central

Cao, Hongbo; Zhai, Jingbo; Li, Nan; Cao, Hongxia; Lei, Xiang; Mu, Wei; Liu, Zhi; Wang, Hui; Shang, Hongcai

2014-01-01

Introduction Traditional Chinese medicine (TCM) has accumulated some experience in curing stable angina pectoris (SAP) and efficacy has been demonstrated. Chinese patent medicines, known as modern dosage forms of TCM, can attain the desired effect in clinical application only with the guidance of TCM syndrome theory. However, due to their use by a large number of persons with little knowledge of TCM theories and practices, their efficacy and reputation have been seriously affected. Method and analysis Two common syndrome types of SAP in TCM, ‘qi deficiency and blood stasis’ and ‘qi stagnation and blood stasis’, will be studied in 144 subjects from four TCM hospitals in Tianjin in China using a partial crossover design. The two syndromes will be broken down into six symptom combinations; patients will select a combination of the most distressing to them, and then will be randomised into two groups. Each group, on the basis of routine medication, will be administered one kind of Chinese patent drug: Qishenyiqi Dripping Pills or Compound Danshen Dripping Pills. The treatment characteristics of the two medicines will be evaluated with the COME-PIO method developed by our research team. Ethics and dissemination This protocol has been approved by the medical ethics committee of Tianjin University of TCM (registration number TJUTCM-EC20130005). The study is safe and reliable. Trial registration number Chinese clinical trials register ChiCTR-TTRCC-14004406. PMID:25431225

Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation

PubMed Central

Taranto-Montemurro, Luigi; Sands, Scott A.; Edwards, Bradley A.; Azarbarzin, Ali; Marques, Melania; de Melo, Camila; Eckert, Danny J.; White, David P.; Wellman, Andrew

2017-01-01

We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea–hypopnea index (AHI) in OSA patients. A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V′0,passive) and active (V′0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP. Desipramine reduced active Pcrit (median (interquartile range) −5.2 (4.3) cmH2O on desipramine versus −1.9 (2.7) cmH2O on placebo; p=0.049) but not passive Pcrit (−2.2 (3.4) versus −0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined as V′0,active−V′0, passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009). In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation. PMID:27799387

Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; van der Veen, F

2004-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in these women. Although ovulation and pregnancy have been achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been clearly demonstrated. To assess the effectiveness of pulsatile GnRH administration in women with polycystic ovary syndrome (PCOS), in terms of ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched 13 August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. All relevant published randomised clinical trials were selected for inclusion if treatment consisted of pulsatile GnRH administration versus another treatment for ovulation induction in subfertile women with PCOS. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto method. Four randomised clinical trials involving 57 women were identified comparing four different treatments: GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus clomiphene citrate. This means that there was only one trial in any one comparison. In two studies, data of pre- and post-crossover were not described separately. All trials were small and of too short duration to show any significant differences in pregnancy results. The odds ratio for ongoing pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation syndrome was seen only in women allocated to ovulation induction with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Inhaled mannitol for cystic fibrosis.

PubMed

Nolan, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

2015-10-09

Several agents are used to clear secretions from the airways of people with cystic fibrosis. Inhaled dry powder mannitol is now available in Australia and some countries in Europe. The exact mechanism of action of mannitol is unknown, but it increases mucociliary clearance. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 16 April 2015. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The searches identified nine separate studies (45 publications), of which four studies (36 publications) were included with a total of 667 participants, one study (only available as an abstract) is awaiting assessment and two studies are ongoing. Duration of treatment in the included studies ranged from two weeks to six months with open-label treatment for an additional six months in two of the studies. Three studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol); two of these were parallel studies with a similar design and data could be pooled, where data for a particular outcome and time point were available; also, one short-term cross-over study supplied additional results. The fourth study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. There was generally a low risk of bias in relation to randomisation and blinding; evidence from the parallel studies was judged to be of low to moderate quality and from the cross-over studies was judged to be of low to very low quality. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. There was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised to the studies; therefore the study results are not applicable to the cystic fibrosis population as a whole.For the comparison of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains, except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. Up to and including six months, lung function in terms of forced expiratory volume at one second (millilitres) and per cent predicted were significantly improved in all three studies comparing mannitol to control. Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non users. A significant reduction was shown in the incidence of pulmonary exacerbations in favour of mannitol at six months; however, the estimate of this effect was imprecise so it is unclear whether the effect is clinically meaningful. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects on both treatments. Mannitol was not associated with any increase in isolation of bacteria over a six-month period.In the 12-week cross-over study (28 participants), no significant differences were found in the recorded domains of health-related quality of life or measures of lung function between mannitol versus dornase alfa alone and versus mannitol plus dornase alfa. There seemed to be a higher rate of pulmonary exacerbations in the mannitol plus dornase alfa arm compared with dornase alfa alone; although not statistically significant, this was the most common reason for stopping treatment in this arm. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. Mannitol (with or without dornase alfa) was not associated with any increase in isolation of bacteria over the 12-week period. There is evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is no evidence that quality of life is improved for participants taking mannitol compared to control; a decrease in burden of treatment was observed up to four months on mannitol compared to control but this difference was not maintained to six months. Randomised information regarding the burden of adding mannitol to an existing treatment is limited. There is no randomised evidence of improvement in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa.Mannitol as a single or concomitant treatment to dornase alfa may be of benefit to people with cystic fibrosis, but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term.The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; however, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice.

Is a controlled randomised trial the non-plus-ultra design? A contribution to discussion on comparative, controlled, non-randomised trials.

PubMed

Gaus, Wilhelm; Muche, Rainer

2013-05-01

Clinical studies provide formalised experience for evidence-based medicine (EBM). Many people consider a controlled randomised trial (CRT, identical to a randomised controlled trial RCT) to be the non-plus-ultra design. However, CRTs also have limitations. The problem is not randomisation itself but informed consent for randomisation and masking of therapies according to today's legal and ethical standards. We do not want to de-rate CRTs, but we would like to contribute to the discussion on clinical research methodology. Informed consent to a CRT and masking of therapies plainly select patients. The excellent internal validity of CRTs can be counterbalanced by poor external validity, because internal and external validity act as antagonists. In a CRT, patients may feel like guinea pigs, this can decrease compliance, cause protocol violations, reduce self-healing properties, suppress unspecific therapeutic effects and possibly even modify specific efficacy. A control group (comparative study) is most important for the degree of evidence achieved by a trial. Study control by detailed protocol and good clinical practice (controlled study) is second in importance and randomisation and masking is third (thus the sequence CRT instead of RCT). Controlled non-randomised trials are just as ambitious and detailed as CRTs. We recommend clinicians and biometricians to take high quality controlled non-randomised trials into consideration more often. They combine good internal and external validity, better suit daily medical practice, show better patient compliance and fewer protocol violations, deliver estimators unbiased by alienated patients, and perhaps provide a clearer explanation of the achieved success. Copyright © 2013 Elsevier Inc. All rights reserved.

Baclofen for alcohol withdrawal.

PubMed

Liu, Jia; Wang, Lu-Ning

2017-08-20

Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence). No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.

Continuous versus bolus intragastric tube feeding for preterm and low birth weight infants with gastro-oesophageal reflux disease.

PubMed

Richards, Robyn; Foster, Jann P; Psaila, Kim

2014-07-17

Gastro-oesophageal reflux disease is a particularly common condition in preterm and low birth weight infants. These infants are also more likely to have excessive regurgitation, as they do not have a fully developed antireflux mechanism. Preterm and low birth weight infants who are unable to suck oral feeds are required to be fed via an intragastric tube for varying lengths of time. Intragastric tube feeding can be delivered by the intermittent bolus or continuous feeding method. Use of continuous or intermittent bolus intragastric feeding may have a positive or negative effect on the incidence or severity of gastro-oesophageal reflux disease. To determine whether continuous or intermittent bolus intragastric tube feeding reduces the number of episodes and the duration of gastro-oesophageal reflux disease (GORD) in preterm and low birth weight infants.We intended to perform subgroup analyses for gestational age; birth weight; age in days from birth at full enteral feeding via intragastric tube (breast vs bottle); frequency of intermittent bolus feed; and type of medication for treatment of GORD (only if medication prescribed and given similarly to both intervention groups). We used the standard search strategy of the Cochrane Neonatal Group as described in The Cochrane Library (www.thecochranelibrary.com) to search for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE (1966 to September 2013), EMBASE (1980 to September 2013) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to September 2013). We also searched previous reviews, including cross-references, abstracts and conference and symposia proceedings of the Perinatal Society of Australia and New Zealand and the Pediatric Academic Societies (American Pediatric Society/Society for Pediatric Research and European Society for Paediatric Research) from 1990 to 2012. Published and unpublished RCTs and quasi-RCTs were eligible for inclusion in this review, as were cluster-randomised and cross-over randomised trials that compared the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants. Two review authors independently assessed study eligibility and quality. We found no trials that met the inclusion criteria for this review. We did not identify any randomised trials that evaluated the effects of continuous versus intermittent bolus intragastric tube feeding on gastro-oesophageal reflux disease in preterm and low birth weight infants. Well-designed and adequately powered trials are needed.

The Preservation of Cued Recall in the Acute Mentally Fatigued State: A Randomised Crossover Study.

PubMed

Flindall, Ian Richard; Leff, Daniel Richard; Pucks, Neysan; Sugden, Colin; Darzi, Ara

2016-01-01

The objective of this study is to investigate the impact of acute mental fatigue on the recall of clinical information in the non-sleep-deprived state. Acute mental fatigue in the non-sleep-deprived subject is rarely studied in the medical workforce. Patient handover has been highlighted as an area of high risk especially in fatigued subjects. This study evaluates the deterioration in recall of clinical information over 2 h with cognitively demanding work in non-sleep-deprived subjects. A randomised crossover study involving twenty medical students assessed free (presentation) and cued (MCQ) recall of clinical case histories at 0 and 2 h under low and high cognitive load using the N-Back task. Acute mental fatigue was assessed through the Visual Analogue Scale, Stanford Scale and NASA-TLX Mental Workload Rating Scale. Free recall is significantly impaired by increased cognitive load (p < 0.05) with subjects demonstrating perceived mental fatigue during the high cognitive load assessment. There was no significant difference in the amount of information retrieved by cued recall under high and low cognitive load conditions (p = 1). This study demonstrates the loss of clinical information over a short time period involving a mentally fatiguing, high cognitive load task. Free recall for the handover of clinical information is unreliable. Memory cues maintain recall of clinical information. This study provides evidence towards the requirement for standardisation of a structured patient handover. The use of memory cues (involving recognition memory and cued recall methodology) would be beneficial in a handover checklist to aid recall of clinical information and supports evidence for their adoption into clinical practice.

Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study

PubMed Central

Schweiggert, Ralf M.; Kopec, Rachel E.; Villalobos-Gutierrez, Maria G.; Högel, Josef; Quesada, Silvia; Esquivel, Patricia; Schwartz, Steven J.; Carle, Reinhold

2014-01-01

Carrot, tomato and papaya represent important dietary sources of β-carotene and lycopene. The main objective of the present study was to compare the bioavailability of carotenoids from these food sources in healthy human subjects. A total of sixteen participants were recruited for a randomised cross-over study. Test meals containing raw carrots, tomatoes and papayas were adjusted to deliver an equal amount of β-carotene and lycopene. For the evaluation of bioavailability, TAG-rich lipoprotein (TRL) fractions containing newly absorbed carotenoids were analysed over 9.5 h after test meal consumption. The bioavailability of β-carotene from papayas was approximately three times higher than that from carrots and tomatoes, whereas differences in the bioavailability of β-carotene from carrots and tomatoes were insignificant. Retinyl esters appeared in the TRL fractions at a significantly higher concentration after the consumption of the papaya test meal. Similarly, lycopene was approximately 2.6 times more bioavailable from papayas than from tomatoes. Furthermore, the bioavailability of β-cryptoxanthin from papayas was shown to be 2.9 and 2.3 times higher than that of the other papaya carotenoids β-carotene and lycopene, respectively. The morphology of chromoplasts and the physical deposition form of carotenoids were hypothesised to play a major role in the differences observed in the bioavailability of carotenoids from the foods investigated. Particularly, the liquid-crystalline deposition of β-carotene and the storage of lycopene in very small crystalloids in papayas were found to be associated with their high bioavailability. In conclusion, papaya was shown to provide highly bioavailable β-carotene, β-cryptoxanthin and lycopene and may represent a readily available dietary source of provitamin A for reducing the incidence of vitamin A deficiencies in many subtropical and tropical developing countries. PMID:23931131

Patient ratings of chewing ability from a randomised crossover trial: lingualised vs. first premolar/canine-guided occlusion for complete dentures.

PubMed

Heydecke, Guido; Akkad, Ahmed Shadi; Wolkewitz, Martin; Vogeler, Michael; Türp, Jens C; Strub, Joerg R

2007-06-01

Complex procedures involving a facebow transfer and the use of lingualised teeth are deemed to have a positive influence on the chewing ability with complete dentures. To determine if patients' ratings of their ability to chew depend on the method of complete denture fabrication. Edentulous patients (n = 20) participated in a within-subject crossover trial. Each patient received two sets of new complete dentures. One pair was manufactured based on intraoral tracing of centric relation and facebow transfer; semi-anatomical teeth with lingualised occlusion denture (LOD) were chosen. The second pair was made using a simplified procedure without facebow transfer; jaw relations were recorded with wax occlusion rims, and anatomical teeth with a first premolar/canine-guidance (CGD) were selected. The dentures were delivered in randomised order, and each was worn for 3 months. Three months after delivery, patients' ratings of each new prosthesis were recorded on visual analogue scales for their ability to chew seven index foods. Repeated measurements analysis of variance was performed to investigate possible carry-over effects accounting for confounding by treatment period. When comparing the two treatments, participants rated their ability to chew in general, to masticate carrots, hard sausage, steak and raw apple in particular, was significantly better with the CGD (anatomical teeth) than with the LOD (p < 0.05). Comprehensive methods for the fabrication of complete dentures including semi-anatomical lingualised teeth and a full registration do not seem to influence the perceived chewing ability, when compared with more simple procedures. Chewing ability for tough foods appears to benefit from the use of anatomical teeth.

Preference, satisfaction and critical errors with Genuair and Breezhaler inhalers in patients with COPD: a randomised, cross-over, multicentre study

PubMed Central

Pascual, Sergi; Feimer, Jan; De Soyza, Anthony; Sauleda Roig, Jaume; Haughney, John; Padullés, Laura; Seoane, Beatriz; Rekeda, Ludmyla; Ribera, Anna; Chrystyn, Henry

2015-01-01

Background: The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). Aims: To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use. Methods: Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication. The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire). Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device. Results: Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years). Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs. 27.3%; P<0.001). Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs. 5.3, respectively; P<0.001). After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs. 3.3%, respectively). Conclusions: Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler. The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. PMID:25927321

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study.

PubMed

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. UMIN000034701.

Study for every other day administration of vonoprazan in maintenance treatment of erosive GERD: study protocol for a multicentre randomised cross-over study

PubMed Central

Kato, Mototsugu; Ito, Noriko; Demura, Mamiko; Kubo, Kimitoshi; Mabe, Katsuhiro; Harada, Naohiko

2018-01-01

Introduction The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. Methods and analysis This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. Ethics and dissemination This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). Discussion If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. Trial registration number UMIN000034701. PMID:29527318

Motion detection technology as a tool for cardiopulmonary resuscitation (CPR) quality training: a randomised crossover mannequin pilot study.

PubMed

Semeraro, Federico; Frisoli, Antonio; Loconsole, Claudio; Bannò, Filippo; Tammaro, Gaetano; Imbriaco, Guglielmo; Marchetti, Luca; Cerchiari, Erga L

2013-04-01

Outcome after cardiac arrest is dependent on the quality of chest compressions (CC). A great number of devices have been developed to provide guidance during CPR. The present study evaluates a new CPR feedback system (Mini-VREM: Mini-Virtual Reality Enhanced Mannequin) designed to improve CC during training. Mini-VREM system consists of a Kinect(®) (Microsoft, Redmond, WA, USA) motion sensing device and specifically developed software to provide audio-visual feedback. Mini-VREM was connected to a commercially available mannequin (Laerdal Medical, Stavanger, Norway). Eighty trainees (healthcare professionals and lay people) volunteered in this randomised crossover pilot study. All subjects performed a 2 min CC trial, 1h pause and a second 2 min CC trial. The first group (FB/NFB, n=40) performed CC with Mini-VREM feedback (FB) followed by CC without feedback (NFB). The second group (NFB/FB, n=40) performed vice versa. Primary endpoints: adequate compression (compression rate between 100 and 120 min(-1) and compression depth between 50 and 60mm); compressions rate within 100-120 min(-1); compressions depth within 50-60mm. When compared to the performance without feedback, with Mini-VREM feedback compressions were more adequate (FB 35.78% vs. NFB 7.27%, p<0.001) and more compressions achieved target rate (FB 72.04% vs. 31.42%, p<0.001) and target depth (FB 47.34% vs. 24.87%, p=0.002). The participants perceived the system to be easy to use with effective feedback. The Mini-VREM system was able to improve significantly the CC performance by healthcare professionals and by lay people in a simulated CA scenario, in terms of compression rate and depth. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Randomised crossover trial of rate feedback and force during chest compressions for paediatric cardiopulmonary resuscitation.

PubMed

Gregson, Rachael Kathleen; Cole, Tim James; Skellett, Sophie; Bagkeris, Emmanouil; Welsby, Denise; Peters, Mark John

2017-05-01

To determine the effect of visual feedback on rate of chest compressions, secondarily relating the forces used. Randomised crossover trial. Tertiary teaching hospital. Fifty trained hospital staff. A thin sensor-mat placed over the manikin's chest measured rate and force. Rescuers applied compressions to the same paediatric manikin for two sessions. During one session they received visual feedback comparing their real-time rate with published guidelines. Primary: compression rate. Secondary: compression and residual forces. Rate of chest compressions (compressions per minute (compressions per minute; cpm)) varied widely (mean (SD) 111 (13), range 89-168), with a fourfold difference in variation during session 1 between those receiving and not receiving feedback (108 (5) vs 120 (20)). The interaction of session by feedback order was highly significant, indicating that this difference in mean rate between sessions was 14 cpm less (95% CI -22 to -5, p=0.002) in those given feedback first compared with those given it second. Compression force (N) varied widely (mean (SD) 306 (94); range 142-769). Those receiving feedback second (as opposed to first) used significantly lower force (adjusted mean difference -80 (95% CI -128 to -32), p=0.002). Mean residual force (18 N, SD 12, range 0-49) was unaffected by the intervention. While visual feedback restricted excessive compression rates to within the prescribed range, applied force remained widely variable. The forces required may differ with growth, but such variation treating one manikin is alarming. Feedback technologies additionally measuring force (effort) could help to standardise and define effective treatments throughout childhood. 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/.

Thermal build-up, decay and retention responses to local therapeutic application of 448 kHz capacitive resistive monopolar radiofrequency: A prospective randomised crossover study in healthy adults.

PubMed

Kumaran, Binoy; Watson, Tim

2015-01-01

Radiofrequency-based electrophysical agents are widely used in therapy-related clinical practice for their thermal effects, mainly relieving pain and inflammation and improving tissue extensibility. The most commonly used and researched are shortwave therapies that operate at 27.12 MHz. Although relatively new, electrophysical agents employing much lower frequencies have also emerged. Capacitive resistive monopolar radiofrequency employing 448 kHz is one such therapy. This laboratory-based study was aimed to investigate the skin thermal responses to 448 kHz radiofrequency-based therapy in healthy adults. In a two-group randomised crossover study, 15 volunteers attended two modes (capacitive and resistive) of 448 kHz radiofrequency-based therapy (using 'Indiba Activ 902') administered locally to the lower thigh region. Starting at minimum, the intensity was increased incrementally until thermal discomfort was felt. Participants reported three time points: thermal onset, definite thermal sensation, and onset of thermal discomfort. Local skin temperature was measured before, immediately post-treatment and up to 45 min post-treatment. Both capacitive and resistive modes of therapy significantly increased the skin temperature and sustained it over the 45-min follow-up. There was statistically significant difference between the thermal response patterns produced by the two modes. Peak post-treatment temperatures attained were not significantly different between the two; however, the retention rate at follow-up was significantly higher for the resistive mode. This study confirms that radiofrequency-based therapy at 448 kHz can significantly increase and sustain skin temperature. The study also provides useful baseline data for further research in the low frequency ranges of radiofrequency-based therapy that remain largely unexplored.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

PubMed Central

Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

2015-01-01

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life. PMID:26038960

A randomised crossover trial of minimising medical terminology in secondary care correspondence in patients with chronic health conditions: impact on understanding and patient reported outcomes.

PubMed

Wernick, M; Hale, P; Anticich, N; Busch, S; Merriman, L; King, B; Pegg, T

2016-05-01

There is little existing research on the role that secondary care letters have in ensuring patient understanding of chronic health conditions. To determine whether minimising the use of medical terminology in medical correspondence improved patient understanding and anxiety/depression scores. A single-centre, non-blinded, randomised crossover design assessed health literacy, EQ-5D scores and the impact of the 'translated' letter on the doctor's professionalism, the patient's relationship with their general practitioner (GP) and their perceived impact on chronic disease management. Patients were crossed over between their 'translated' and original letter. Sixty patients were recruited. Use of a 'translated' letter reduced mean terms not understood from 7.78 to 1.76 (t(58) = 4.706, P < 0.001). Most patients (78.0%) preferred the 'translated' letter, with 69.5% patients perceiving an enhancement in their doctor's professionalism (z = 2.864, P = 0.004), 69.0% reporting a positive influence on relationship with their GP (z = 2.943, P = 0.003) and 79.7% reporting an increase in perceived ability to manage their chronic health condition with the 'translated' letter (z = 4.601, P < 0.001). There was no effect on EQ-5D depression/anxiety scores. Minimising the use of medical terminology in medical correspondence significantly improved patient understanding and perception of their ability to manage their chronic health condition. Although there was no impact on EQ-5D depression/anxiety scores, overwhelming patient preference for the 'translated' letter indicates a need for minimisation of medical terminology in medical correspondence for patients with chronic health conditions. © 2016 Royal Australasian College of Physicians.

Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners.

PubMed

Lund Rasmussen, Charlotte; Nielsen, Line; Linander Henriksen, Marie; Søgaard, Karen; Krustrup, Peter; Holtermann, Andreas; Korshøj, Mette

2018-02-01

High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners. Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models. After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered. A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.

Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study.

PubMed

Hempel, Judith; Fischer, Anja; Fischer, Monique; Högel, Josef; Bosy-Westphal, Anja; Carle, Reinhold; Schweiggert, Ralf M

2017-11-01

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognised in vitro digestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to our in vivo results. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining our in vitro and in vivo observations, the effect of the different aggregation forms on human bioavailability was lower than expected.

Vaccine testing for emerging infections: the case for individual randomisation

PubMed Central

Eyal, Nir; Lipsitch, Marc

2017-01-01

During the 2014–2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible—and it often will be—it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise—requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants’ prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial. PMID:28396558

Evaluation of personalised, one-to-one interaction using Montessori-type activities as a treatment of challenging behaviours in people with dementia: the study protocol of a crossover trial

PubMed Central

2010-01-01

Background The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out) are stressful to both nursing home residents and their carers and are difficult to treat. Behaviours stemming from pain, major depression or psychosis benefit from treatment with analgesics, antidepressants or antipsychotics. In other cases, psychotropic medications have limited efficacy but are used very widely. Therefore, increasingly more attention has been paid to nonpharmacological interventions which are associated with fewer risks. The aim of the current study is to test if personalised one-to-one interaction activities based on Montessori principles will reduce the frequency of behavioural symptoms of dementia significantly more than a relevant control condition. Methods/Design We will conduct a controlled trial with randomised cross-over between conditions. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to Montessori or control blocks for two weeks then switched to the other condition. Montessori activities derive from the principles espoused by Maria Montessori and subsequent educational theorists to promote engagement in learning, namely task breakdown, guided repetition, progression in difficulty from simple to complex, and the careful matching of demands to levels of competence. The control intervention consists of conversation or reading from and looking at pictures in a newspaper to control for non-specific benefits of one-to-one interaction. Presence of target behaviour will be noted as well as level of engagement and type of affect displayed. Secondary measures also include the Cohen-Mansfield Agitation Inventory and information on time and funds spend to prepare the activities. Discussion If our results show that use of Montessori activities is effective in treating challenging behaviours in individuals with dementia, it will potentially provide a safer and more enjoyable intervention rather than reliance on pharmacology alone. Trial Registration Australian New Zealand Clinical Trials Registry - ACTRN12609000564257 PMID:20096137

Outpatient 60-hour day-and-night glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or sensor-augmented pump therapy in adults with type 1 diabetes: An open-label, randomised, crossover, controlled trial.

PubMed

Haidar, Ahmad; Messier, Virginie; Legault, Laurent; Ladouceur, Martin; Rabasa-Lhoret, Rémi

2017-05-01

To assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared to the single-hormone (insulin alone) artificial pancreas in outpatient settings during the day and night. In a randomized, three-way, crossover trial we compared the dual-hormone artificial pancreas, the single-hormone artificial pancreas and sensor-augmented pump therapy (control) in 23 adults with type 1 diabetes. Each intervention was applied from 8 AM Day 1 to 8 PM Day 3 (60 hours) in outpatient free-living conditions. The primary outcome was time spent with sensor glucose levels below 4.0 mmol/L. A P value of less than .017 was regarded as significant. The median difference between the dual-hormone system and the single-hormone system was -2.3% (P = .072) for time spent below 4.0 mmol/L, -1.3% (P = .017) for time below 3.5 mmol/L, and -0.7% (P = .031) for time below 3.3 mmol/L. Both systems reduced (P < .017) hypoglycaemia below 4.0, 3.5 and 3.3 mmol/L compared to control therapy, but reductions were larger with the dual-hormone system than with the single-hormone system (medians -4.0% vs -3.4% for 4.0 mmol/L; -2.7% vs -2.2% for 3.5 mmol/L; and -2.2% vs -1.2% for 3.3 mmol/L). There were 34 hypoglycaemic events (<3.0 mmol/L for 20 minutes) with control therapy, 14 with the single-hormone system and 6 with the dual-hormone system. These differences in hypoglycaemia were observed while mean glucose level was low and comparable in all interventions (P = NS). The dual-hormone artificial pancreas had the lowest risk of hypoglycaemia, but the differences were not statistically significant. Larger studies are needed. © 2017 John Wiley & Sons Ltd.

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers.

PubMed

Vauzour, David; Houseman, Emily J; George, Trevor W; Corona, Giulia; Garnotel, Roselyne; Jackson, Kim G; Sellier, Christelle; Gillery, Philippe; Kennedy, Orla B; Lovegrove, Julie A; Spencer, Jeremy P E

2010-04-01

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

Liking of health-functional foods containing lupin kernel fibre following repeated consumption in a dietary intervention setting.

PubMed

Hall, Ramon S; Baxter, Amynta L; Fryirs, Cathy; Johnson, Stuart K

2010-10-01

Liking of a particular food after repeated consumption may be reduced, limiting the effectiveness of health-functional foods requiring on-going consumption to deliver their benefits. This study examined the effect of repeated consumption of foods containing the novel ingredient, Australian sweet lupin (Lupinus angustifolius) kernel fibre (LKFibre) on sensory acceptability in the dietary intervention setting. In a single-blind randomised crossover 4-week intervention, participants consumed both control and equivalent LKFibre-containing products daily on separate interventions separated by a 4-week period on habitual diet. Seven products: muesli, bread, muffin, chocolate brownie, chocolate milk drink, pasta and instant mashed potato were assessed twice (days 4 and 18 of intervention), by 38 participants for appearance, texture, flavour and general acceptability using a structured graphic hedonic scale. Overall the results showed there was no reduction (P=0.594) in general acceptability of LKFibre foods after repeated consumption, suggesting potential for long-term consumption. The control food products were however generally preferred (P<0.001) over the LKFibre foods; the mean difference for general acceptability between being <6% (0.82cm) of the 15cm hedonic scale used, suggesting LKF addition did not severely affect product palatability.

Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial

PubMed Central

Eichenseer, M.; Johansen, C.; Mueller, R. S.

2013-01-01

Antihistaminic drugs are commonly used as symptomatic therapy of atopic dermatitis in dogs. Unfortunately, their clinical benefit is largely unsubstantiated. In a double-blinded, placebo-controlled, cross-over trial, the influence of dimetinden and of a combination of chlorpheniramine and hydroxyzine on pruritus and lesions was evaluated in 19 dogs. They were treated with either product or a placebo orally for 14 days, each time followed by a 14-day washout period. Before and after each period, the dogs were examined and the Canine Atopic Dermatitis Extent and Severity Index (CADESI) determined by a clinician, and the pruritus and general condition by the owner. Dimetinden improved the pruritus significantly (P=0.014) but not the CADESI (P=0.087), the combination of hydroxyzine and chlorpheniramine improved the CADESI (P=0.049) and pruritus (P=0.05) significantly. Ten of 17 dogs improved by more than 25 per cent in pruritus with the combination of hydroxyzine and chlorpheniramine, 12 of 18 with dimetindenmaleate and only 2 of 19 with placebo. Antihistamines can help to reduce pruritus in atopic dogs, but in most cases, the improvement is limited and additional treatment may be needed. PMID:24114734

Use of helium-oxygen mixture in adult patients presenting with exacerbations of asthma and chronic obstructive pulmonary disease: a systematic review.

PubMed

Colebourn, C L; Barber, V; Young, J D

2007-01-01

We examined systematically all controlled and cross-over randomised trials in patients with acute exacerbations of asthma and chronic obstructive pulmonary disease comparing Heliox against air-oxygen mixtures. Fourteen studies were identified. In asthma studies, peak expiratory flow rate (PEFR) was increased by an average of 29.6% (95% CI 16.6-42.6) by Heliox-driven nebulisers, or by 13.3 l.min(-1) (95% CI 3.71-22.81) absolute. In studies of patients with chronic obstructive pulmonary disease receiving non-invasive ventilation the arterial carbon dioxide tension (P(a)co(2)) and respiratory rate were unchanged: weighted mean difference for P(a)co(2)-0.29kPa (95% CI - 0.64-0.07) favoured Heliox, and for respiratory rate 1.6 breaths.min(-1) (95% CI - 0.93, 4.14) favoured control. Heliox minimally reduced the work of breathing in intubated patients, and reduced intrinsic positive end expiratory pressure (iPEEP). The use of Heliox to drive nebulisers in patients with acute asthma slightly improves airflow measures. We were unable to determine whether this improved recovery.

Minimalist, standard and no footwear on static and dynamic postural stability following jump landing.

PubMed

Zech, Astrid; Argubi-Wollesen, Andreas; Rahlf, Anna-Lina

2015-01-01

In recreational sports, uncushioned, light-weight and minimalist shoes are increasingly used to imitate barefoot situations. Uncertainty exists whether these shoes provide sufficient stability during challenging movements. In this randomised crossover study, 35 healthy distance runners performed jump landing stabilisation and single-leg stance tests on a force plate, using four conditions in random order: barefoot, uncushioned minimalist shoes, cushioned ultraflexible shoes and standard running shoes. Ground reaction force (GRF) and centre of pressure (COP) data were used to determine unilateral jump landing stabilisation time and COP sway velocity during single-leg stance. Repeated measures analysis of variance revealed significant footwear interactions for medial-lateral (p < 0.001) and anterior-posterior COP sway velocity during standing (p < 0.001). The barefoot condition produced significantly greater postural sway velocities (p < 0.001) compared to all footwear conditions. No significant effects were found for jump landing stabilisation time. In conclusion, the results of this study indicate that increased shoe flexibility and reduced sole support have no, or only minor influence on static and dynamic postural control, and therefore, may not increase the risk of traumatic events during sports activities. However, barefoot conditions should be considered carefully when adequate postural control is needed.

New and old ways to control meiotic recombination.

PubMed

Phadnis, Naina; Hyppa, Randy W; Smith, Gerald R

2011-10-01

The unique segregation of homologs, rather than sister chromatids, at the first meiotic division requires the formation of crossovers (COs) between homologs by meiotic recombination in most species. Crossovers do not form at random along chromosomes. Rather, their formation is carefully controlled, both at the stage of formation of DNA double-strand breaks (DSBs) that can initiate COs and during the repair of these DSBs. Here, we review control of DSB formation and two recently recognized controls of DSB repair: CO homeostasis and CO invariance. Crossover homeostasis maintains a constant number of COs per cell when the total number of DSBs in a cell is experimentally or stochastically reduced. Crossover invariance maintains a constant CO density (COs per kb of DNA) across much of the genome despite strong DSB hotspots in some intervals. These recently uncovered phenomena show that CO control is even more complex than previously suspected. Copyright © 2011 Elsevier Ltd. All rights reserved.

DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.

PubMed

Yelina, Nataliya E; Lambing, Christophe; Hardcastle, Thomas J; Zhao, Xiaohui; Santos, Bruno; Henderson, Ian R

2015-10-15

During meiosis, homologous chromosomes undergo crossover recombination, which is typically concentrated in narrow hot spots that are controlled by genetic and epigenetic information. Arabidopsis chromosomes are highly DNA methylated in the repetitive centromeres, which are also crossover-suppressed. Here we demonstrate that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. However, loss of CG DNA methylation maintenance in met1 triggers epigenetic crossover remodeling at the chromosome scale, with pericentromeric decreases and euchromatic increases in recombination. We used recombination mutants that alter interfering and noninterfering crossover repair pathways (fancm and zip4) to demonstrate that remodeling primarily involves redistribution of interfering crossovers. Using whole-genome bisulfite sequencing, we show that crossover remodeling is driven by loss of CG methylation within the centromeric regions. Using cytogenetics, we profiled meiotic DNA double-strand break (DSB) foci in met1 and found them unchanged relative to wild type. We propose that met1 chromosome structure is altered, causing centromere-proximal DSBs to be inhibited from maturation into interfering crossovers. These data demonstrate that DNA methylation is sufficient to silence crossover hot spots and plays a key role in establishing domains of meiotic recombination along chromosomes. © 2015 Yelina et al.; Published by Cold Spring Harbor Laboratory Press.

Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

PubMed

Li, Xue; Meng, Xiangrui; Timofeeva, Maria; Tzoulaki, Ioanna; Tsilidis, Konstantinos K; Ioannidis, John PA; Campbell, Harry; Theodoratou, Evropi

2017-06-07

Objective  To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design  Umbrella review. Data sources  Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria  Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results  57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10 -6 , 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion  Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of a low dose whey/guar preload on glycemic control in people with type 2 diabetes--a randomised controlled trial.

PubMed

Clifton, Peter M; Galbraith, Claire; Coles, Leah

2014-10-25

Large preloads of protein and fat have been shown to lower glucose after a carbohydrate-rich meal in people with type 2 diabetes but add a considerable energy burden. Low calorie preloads [<5% of daily energy intake] have been tested in this study in people with prediabetes and with type 2 diabetes. This was an unblinded randomised crossover study with two placebo days and two active treatment days. Glucose was measured for 3 hours with fingerprick samples as well as continuous glucose monitoring [CGMS]. Twenty-four subjects with pre-diabetes or moderately controlled type 2 diabetes [fasting glucose < 10 and HbA1c < 8.5%] were recruited. The preload contained 17 g whey protein plus 3 g lactose and 5 g guar, and 1 g flavour material [including sucralose] dissolved in 150 ml cold water or 150 ml cold water with no additives. The breakfast test meal consisted of 2 slices of bread, margarine and jam [3 slices for men] with the test drink 15 minutes beforehand. Peak fingerprick glucose was reduced by 2.1 mmol/L at 45 min [p < 0.0001]. Average fingerprick glucose over 3 hours was reduced by 0.8 mmol/L [p = 0.0003]. There was no difference between those with diabetes or prediabetes or those on medication or not on medication. An 80 kcal whey protein/fibre preload can lower average glucose over 3 hours by 0.8 mmol/L. If used long term before at least two carbohydrate-rich meals/day this preload could lower HbA1c by up to 1%. The trial was registered with the Australian New Zealand Clinical Trials Registry number ACTRN12612001251819.

Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes.

PubMed

Duvivier, Bernard M F M; Schaper, Nicolaas C; Hesselink, Matthijs K C; van Kan, Linh; Stienen, Nathalie; Winkens, Bjorn; Koster, Annemarie; Savelberg, Hans H C M

2017-03-01

We aimed to examine the effects of breaking sitting with standing and light-intensity walking vs an energy-matched bout of structured exercise on 24 h glucose levels and insulin resistance in patients with type 2 diabetes. In a randomised crossover study, 19 patients with type 2 diabetes (13 men/6 women, 63 ± 9 years old) who were not using insulin each followed three regimens under free-living conditions, each lasting 4 days: (1) Sitting: 4415 steps/day with 14 h sitting/day; (2) Exercise: 4823 steps/day with 1.1 h/day of sitting replaced by moderate- to vigorous-intensity cycling (at an intensity of 5.9 metabolic equivalents [METs]); and (3) Sit Less: 17,502 steps/day with 4.7 h/day of sitting replaced by standing and light-intensity walking (an additional 2.5 h and 2.2 h, respectively, compared with the hours spent doing these activities in the Sitting regimen). Blocked randomisation was performed using a block size of six regimen orders using sealed, non-translucent envelopes. Individuals who assessed the outcomes were blinded to group assignment. Meals were standardised during each intervention. Physical activity and glucose levels were assessed for 24 h/day by accelerometry (activPAL) and a glucose monitor (iPro2), respectively. The incremental AUC (iAUC) for 24 h glucose (primary outcome) and insulin resistance (HOMA2-IR) were assessed on days 4 and 5, respectively. The iAUC for 24 h glucose (mean ± SEM) was significantly lower during the Sit Less intervention than in Sitting (1263 ± 189 min × mmol/l vs 1974 ± 324 min × mmol/l; p = 0.002), and was similar between Sit Less and Exercise (Exercise: 1383 ± 194 min × mmol/l; p = 0.499). Exercise failed to improve HOMA2-IR compared with Sitting (2.06 ± 0.28 vs 2.16 ± 0.26; p = 0.177). In contrast, Sit Less (1.89 ± 0.26) significantly reduced HOMA2-IR compared with Exercise (p = 0.015) as well as Sitting (p = 0.001). Breaking sitting with standing and light-intensity walking effectively improved 24 h glucose levels and improved insulin sensitivity in individuals with type 2 diabetes to a greater extent than structured exercise. Thus, our results suggest that breaking sitting with standing and light-intensity walking may be an alternative to structured exercise to promote glycaemic control in patients type 2 diabetes. Clinicaltrials.gov NCT02371239 FUNDING: : The study was supported by a Kootstra grant from Maastricht University Medical Centre + , and the Dutch Heart Foundation. Financial support was also provided by Novo Nordisk BV, and Medtronic and Roche made the equipment available for continuous glucose monitoring.

Intramyocellular lipid content in subjects with impaired fasting glucose after telmisartan treatment, a randomised cross-over trial.

PubMed

Kratochvílová, Simona; Škoch, Antonín; Wohl, Petr; Švehlíková, Eva; Dezortová, Monika; Hill, Martin; Hájek, Milan; Pelikánová, Terezie

2016-04-01

Ectopic lipid accumulation in skeletal muscle is associated with insulin resistance. Telmisartan improves metabolic parameters in type 2 diabetic patients. The aim of our study was to evaluate the in vivo effect of telmisartan on intramyocellular lipid content (IMCL) in subjects with impaired fasting glucose (IFG) by magnetic resonance spectroscopy (MRS). We enrolled 10 subjects with IFG in a cross-over, placebo-controlled, randomized, double-blind trial, treated with 3 weeks of telmisartan (160 mg daily) or placebo. After completing each treatment, a hyperinsulinaemic euglycaemic clamp (1 mU/kg per min; 5 mmol/l; 120 min) to assess insulin action (metabolic clearance rate of glucose, MCR) and (1)H MRS of the m. tibialis anterior using a MR Scanner Siemens Vision operating at 1.5 T to evaluate IMCL content, were performed. Plasma adipokine levels were determined simultaneously. Telmisartan treatment resulted in a lower fasting plasma glucose (FPG) (p < 0.05), but insulin action was comparable to after placebo. Telmisartan did not affect IMCL content. After placebo, IMCL correlated negatively with total cholesterol (p < 0.001), MCR (p < 0.05) and adiponectin (p < 0.05) and positively with FPG (p < 0.05). After telmisartan treatment there was only a positive correlation between IMCL and TNFα (p < 0.05). IMCL content is related to parameters of glucose metabolism and insulin action in sedentary IFG subjects. A short telmisartan treatment did not affect the IMCL content despite its positive effect on FPG. The improvement in FPG was probably mediated through interference with other metabolic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Endocannabinoids and related lipids in blood plasma following touch massage: a randomised, crossover study.

PubMed

Lindgren, Lenita; Gouveia-Figueira, Sandra; Nording, Malin L; Fowler, Christopher J

2015-09-29

The endocannabinoid system is involved in the regulation of stress and anxiety. In a recent study, it was reported that short-term changes in mood produced by a pleasant ambience were correlated with changes in the levels of plasma endocannabinoids and related N-acylethanolamines (Schrieks et al. PLoS One 10: e0126421, 2015). In the present study, we investigated whether stress reduction by touch massage (TM) affects blood plasma levels of endocannabinoids and related N-acylethanolamines. A randomized two-session crossover design for 20 healthy participants was utilised, with one condition that consisted of TM and a rest condition as control. TM increased the perceived pleasantness rating of the participants, and both TM and rest reduced the basal anxiety level as assessed by the State scale of the STAI-Y inventory. However, there were no significant effects of either time (pre- vs. post-treatment measures) as main effect or the interaction time x treatment for the plasma levels of the endocannabinoids anandamide and 2-arachidonoylglycerol or for eight other related lipids. Four lipids showed acceptable relative reliabilities, and for two of these (linoleoyl ethanolamide and palmitoleoyl ethanolamide) a significant correlation was seen between the TM-related change in levels, calculated as (post-TM value minus pre-TM value) - (post-rest value minus pre-rest value), and the corresponding TM-related change in perceived pleasantness. It is concluded that in the participants studied here, there are no overt effects of TM upon plasma endocannabinoid levels. Possible associations of related N-acylethanolamines with the perceived pleasantness should be investigated further.

Breakfast replacement with a low-glycaemic response liquid formula in patients with type 2 diabetes: a randomised clinical trial.

PubMed

Stenvers, Dirk J; Schouten, Lydia J; Jurgens, Jordy; Endert, Erik; Kalsbeek, Andries; Fliers, Eric; Bisschop, Peter H

2014-08-28

Low-glycaemic index diets reduce glycated Hb (HbA1c) in patients with type 2 diabetes, but require intensive dietary support. Using a liquid meal replacement with a low glycaemic response (GR) may be an alternative dietary approach. In the present study, we investigated whether breakfast replacement with a low-GR liquid meal would reduce postprandial glycaemia and/or improve long-term glycaemia. In the present randomised, controlled, cross-over design, twenty patients with type 2 diabetes consumed either a breakfast replacement consisting of an isoenergetic amount of Glucerna SR or a free-choice breakfast for 3 months. Postprandial AUC levels were measured using continuous glucose measurement at home. After the 3-month dietary period, meal profiles and oral glucose tolerance were assessed in the clinical setting. The low-GR liquid meal replacement reduced the AUC of postprandial glucose excursions at home compared with a free-choice control breakfast (estimated marginal mean 141 (95 % CI 114, 174) v. estimated marginal mean 259 (95 % CI 211, 318) mmol × min/l; P= 0·0002). The low-GR liquid meal replacement also reduced glucose AUC levels in the clinical setting compared with an isoenergetic control breakfast (low GR: median 97 (interquartile range (IQR) 60-188) mmol × min/l; control: median 253 (IQR 162-386) mmol × min/l; P< 0·001). However, the 3-month low-GR liquid meal replacement did not affect fasting plasma glucose, HbA1c or lipid levels, and even slightly reduced oral glucose tolerance. In conclusion, the low-GR liquid meal replacement is a potential dietary approach to reduce postprandial glycaemia in patients with type 2 diabetes. However, clinical trials into the effects of replacing multiple meals on long-term glycaemia in poorly controlled patients are required before a low-GR liquid meal replacement can be adopted as a dietary approach to the treatment of type 2 diabetes.

Dietary supplementation with a natural carotenoid mixture decreases oxidative stress.

PubMed

Kiokias, S; Gordon, M H

2003-09-01

To determine whether dietary supplementation with a natural carotenoid mixture counteracts the enhancement of oxidative stress induced by consumption of fish oil. A randomised double-blind crossover dietary intervention. Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights PO Box 226, Reading RG6 6AP, UK. A total of 32 free-living healthy nonsmoking volunteers were recruited by posters and e-mails in The University of Reading. One volunteer withdrew during the study. The volunteers consumed a daily supplement comprising capsules containing fish oil (4 x 1 g) or fish oil (4 x 1 g) containing a natural carotenoid mixture (4 x 7.6 mg) for 3 weeks in a randomised crossover design separated by a 12 week washout phase. The carotenoid mixture provided a daily intake of beta-carotene (6.0 mg), alpha-carotene (1.4 mg), lycopene (4.5 mg), bixin (11.7 mg), lutein (4.4 mg) and paprika carotenoids (2.2 mg). Blood and urine samples were collected on days 0 and 21 of each dietary period. The carotenoid mixture reduced the fall in ex vivo oxidative stability of low-density lipoprotein (LDL) induced by the fish oil (P=0.045) and it reduced the extent of DNA damage assessed by the concentration of 8-hydroxy-2'-deoxyguanosine in urine (P=0.005). There was no effect on the oxidative stability of plasma ex vivo assessed by the oxygen radical absorbance capacity test. beta-Carotene, alpha-carotene, lycopene and lutein were increased in the plasma of subjects consuming the carotenoid mixture. Plasma triglyceride levels were reduced significantly more than the reduction for the fish oil control (P=0.035), but total cholesterol, HDL and LDL levels were not significantly changed by the consumption of the carotenoid mixture. Consumption of the natural carotenoid mixture lowered the increase in oxidative stress induced by the fish oil as assessed by ex vivo oxidative stability of LDL and DNA degradation product in urine. The carotenoid mixture also enhanced the plasma triglyceride-lowering effect of the fish oil. : The study was supported by funding from the Greek Studentship Foundation and from Unilever Bestfoods plc. Carotenoids were contributed by Overseal Foods plc.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

Effect of tube drainage compared with conventional suturing on postoperative discomfort after extraction of impacted mandibular third molars.

PubMed

Koyuncu, B Ö; Zeytinoğlu, M; Tetik, A; Gomel, M M

2015-01-01

The aim of this prospective randomised study was to assess the effects of tube drainage on postoperative discomfort after the extraction of impacted mandibular third molars. We studied 40 patients (11 men and 29 women) 18 years or older (mean (SD) 21 (3), range 18-29) who required extraction of mandibular third molars. We used a randomised crossover design by which if a drain was inserted on one side, then the other side was managed without a drain on a later occasion. Pain, swelling, and mouth opening were evaluated after 48 h and 7 days postoperatively in both groups. Facial swelling (p=0.001), pain p=0.001), and trismus (p=0.001) were significantly less common in the drained group compared with those not drained. We conclude that the use a tube drain is of benefit in minimising postoperative swelling, pain, and trismus after extraction of mandibular third molars. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A systematic examination of preoperative surgery warm-up routines.

PubMed

Pike, T W; Pathak, S; Mushtaq, F; Wilkie, R M; Mon-Williams, M; Lodge, J P A

2017-05-01

Recent evidence indicates that a preoperative warm-up is a potentially useful tool in facilitating performance. But what factors drive such improvements and how should a warm-up be implemented? In order to address these issues, we adopted a two-pronged approach: (1) we conducted a systematic review of the literature to identify existing studies utilising preoperative simulation techniques; (2) we performed task analysis to identify the constituent parts of effective warm-ups. We identified five randomised control trials, four randomised cross-over trials and four case series. The majority of these studies reviewed surgical performance following preoperative simulation relative to performance without simulation. Four studies reported outcome measures in real patients and the remainder reported simulated outcome measures. All but one of the studies found that preoperative simulation improves operative outcomes-but this improvement was not found across all measured parameters. While the reviewed studies had a number of methodological issues, the global data indicate that preoperative simulation has substantial potential to improve surgical performance. Analysis of the task characteristics of successful interventions indicated that the majority of these studies employed warm-ups that focused on the visual motor elements of surgery. However, there was no theoretical or empirical basis to inform the design of the intervention in any of these studies. There is an urgent need for a more rigorous approach to the development of "warm-up" routines if the potential value of preoperative simulation is to be understood and realised. We propose that such interventions need to be grounded in theory and empirical evidence on human motor performance.

Head Position in Stroke Trial (HeadPoST)--sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial.

PubMed

Muñoz-Venturelli, Paula; Arima, Hisatomi; Lavados, Pablo; Brunser, Alejandro; Peng, Bin; Cui, Liying; Song, Lily; Billot, Laurent; Boaden, Elizabeth; Hackett, Maree L; Heritier, Stephane; Jan, Stephen; Middleton, Sandy; Olavarría, Verónica V; Lim, Joyce Y; Lindley, Richard I; Heeley, Emma; Robinson, Thompson; Pontes-Neto, Octavio; Natsagdorj, Lkhamtsoo; Lin, Ruey-Tay; Watkins, Caroline; Anderson, Craig S

2015-06-05

Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥ 30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥ 30°) head position as a 'business as usual' stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014.

High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial.

PubMed

Jakubowicz, Daniela; Wainstein, Julio; Ahrén, Bo; Bar-Dayan, Yosefa; Landau, Zohar; Rabinovitz, Hadas R; Froy, Oren

2015-05-01

High-energy breakfast and reduced-energy dinner (Bdiet) significantly reduces postprandial glycaemia in obese non-diabetic individuals. Our objective was to test whether this meal schedule reduces postprandial hyperglycaemia (PPHG) in patients with type 2 diabetes by enhancing incretin and insulin levels when compared with high-energy dinner and reduced-energy breakfast (Ddiet). In a randomised, open label, crossover design performed in a clinic setting, 18 individuals (aged 30-70 years with BMI 22-35 kg/m(2)) with type 2 diabetes (<10 years duration) treated with metformin and/or diet were given either Bdiet or Ddiet for 7 days. Participants were randomised by a person not involved in the study using a coin flip. Postprandial levels of plasma glucose, insulin, C-peptide and intact and total glucagon-like peptide-1 (iGLP-1 and tGLP-1) were assessed. The Bdiet included 2,946 kJ breakfast, 2,523 kJ lunch and 858 kJ dinner. The Ddiet comprised 858 kJ breakfast, 2,523 kJ lunch and 2,946 kJ dinner. Twenty-two individuals were randomised and 18 analysed. The AUC for glucose (AUCglucose) throughout the day was 20% lower, whereas AUCinsulin, AUCC-peptide and AUCtGLP-1 were 20% higher for the Bdiet than the Ddiet. Glucose AUC0-180min and its peak were both lower by 24%, whereas insulin AUC0-180min was 11% higher after the Bdiet than the Ddiet. This was accompanied by 30% higher tGLP-1 and 16% higher iGLP-1 levels. Despite the diets being isoenergetic, lunch resulted in lower glucose (by 21-25%) and higher insulin (by 23%) with the Bdiet vs Ddiet. High energy intake at breakfast is associated with significant reduction in overall PPHG in diabetic patients over the entire day. This dietary adjustment may have a therapeutic advantage for the achievement of optimal metabolic control and may have the potential for being preventive for cardiovascular and other complications of type 2 diabetes. Trial registration ClinicalTrials.gov NCT01977833 Funding No specific funding was received for the study.

The quality of a newly developed infant chest compression method applied by paramedics: a randomised crossover manikin trial.

PubMed

Smereka, Jacek; Kasiński, Mariusz; Smereka, Adam; Ładny, Jerzy R; Szarpak, Łukasz

2017-01-01

The aetiology of sudden cardiac arrest in infants is different from that in adults, with respiratory failure, sudden infant death syndrome, and drowning being the primary causes in the former. According to the European Resuscitation Council (ERC) and American Heart Association (AHA) recommendations, the quality of chest compressions (CC) is a key element affecting the effectiveness of cardiopulmonary resuscitation (CPR). The current ERC and AHA guidelines recommend the 'two-finger technique' (TFT) or 'two-thumb encircling hands technique' (TTHT) for external CCs during infant CPR. The aim of the randomised crossover manikin trial was to assess the CC quality during simulated resuscitation in infants performed by paramedics. A prospective, randomised, crossover, single-centre study was conducted between June and August 2016. The study material consisted of 120 fully trained and licensed paramedics (39 females, 32.5%) with a minimum of five years of professional experience (mean 7.5 ± 4.8 years) in emergency medicine (mean age, 30.5 ± 5.5 years). The participants performed CCs using three techniques: TFT (the rescuer compresses the sternum with the tips of two fingers); TTHT; and the 'new two-thumb technique' (nTTT). The novel method of CCs in an infant consists of using two thumbs directed at the angle of 90 degrees to the chest while closing the fingers of both hands in a fist. The median CC rate when using the TFT, the TTHT, and nTTT methods varied and amounted to 134 min-1 vs. 126 min-1 vs. 114 min-1, respectively. There was a statistically significant difference in the median CC frequency between TFT and TTHT (p < 0.001), TFT and nTTT (p < 0.001), and between TTHT and nTTT (p < 0.001). The highest percentage of compressions with the frequency recommended by the ERC guidelines (100-120 min-1) was achieved by the study participants only with the nTTT. The median CC depth during the TFT was 28 mm (interquartile range [IQR] 27-30 mm) and was significantly lower than in the static TTHT (40.5 [IQR 39-41] mm; p < 0.001) and nTTT (40 [IQR 39-41] mm; p < 0.001). The percentage of adequate depth CCs was correctly obtained with TTHT and nTTT. The largest proportion of total decompression of the chest was observed with the nTTT technique (96 [IQR 96-98] %), followed by TFT (95.5 [IQR 85.5-99] %) and TTHT (5 [IQR 3-7] %). In all scenarios, the correct placement of the CC point was achieved in more than 90% of cases. Our novel infant CC method provides the highest percentage of CCs with the frequency recommended by the ERC guidelines as compared with standard techniques. It also allows optimal CC depth.

Vaccine testing for emerging infections: the case for individual randomisation.

PubMed

Eyal, Nir; Lipsitch, Marc

2017-09-01

During the 2014-2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible-and it often will be-it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise-requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants' prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial. 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/.

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

PubMed Central

Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

1998-01-01

OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage.

 PMID:9527146

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

PubMed

Somaraju, Usha Rani; Solis-Moya, Arturo

2016-11-23

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001). There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.

An optimised patient information sheet did not significantly increase recruitment or retention in a falls prevention study: an embedded randomised recruitment trial.

PubMed

Cockayne, Sarah; Fairhurst, Caroline; Adamson, Joy; Hewitt, Catherine; Hull, Robin; Hicks, Kate; Keenan, Anne-Maree; Lamb, Sarah E; Green, Lorraine; McIntosh, Caroline; Menz, Hylton B; Redmond, Anthony C; Rodgers, Sara; Torgerson, David J; Vernon, Wesley; Watson, Judith; Knapp, Peter; Rick, Jo; Bower, Peter; Eldridge, Sandra; Madurasinghe, Vichithranie W; Graffy, Jonathan

2017-03-28

Randomised controlled trials are generally regarded as the 'gold standard' experimental design to determine the effectiveness of an intervention. Unfortunately, many trials either fail to recruit sufficient numbers of participants, or recruitment takes longer than anticipated. The current embedded trial evaluates the effectiveness of optimised patient information sheets on recruitment of participants in a falls prevention trial. A three-arm, embedded randomised methodology trial was conducted within the National Institute for Health Research-funded REducing Falls with ORthoses and a Multifaceted podiatry intervention (REFORM) cohort randomised controlled trial. Routine National Health Service podiatry patients over the age of 65 were randomised to receive either the control patient information sheet (PIS) for the host trial or one of two optimised versions, a bespoke user-tested PIS or a template-developed PIS. The primary outcome was the proportion of patients in each group who went on to be randomised to the host trial. Six thousand and nine hundred patients were randomised 1:1:1 into the embedded trial. A total of 193 (2.8%) went on to be randomised into the main REFORM trial (control n = 62, template-developed n = 68; bespoke user-tested n = 63). Information sheet allocation did not improve recruitment to the trial (odds ratios for the three pairwise comparisons: template vs control 1.10 (95% CI 0.77-1.56, p = 0.60); user-tested vs control 1.01 (95% CI 0.71-1.45, p = 0.94); and user-tested vs template 0.92 (95% CI 0.65-1.31, p = 0.65)). This embedded methodology trial has demonstrated limited evidence as to the benefit of using optimised information materials on recruitment and retention rates in the REFORM study. International Standard Randomised Controlled Trials Number registry, ISRCTN68240461 . Registered on 01 July 2011.

The joy of six: how to control your crossovers.

PubMed

Globus, Samuel T; Keeney, Scott

2012-03-30

Meiotic cells tightly regulate the number and distribution of crossovers to promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan-specific, cyclin-like protein that is crucial for crossover formation. They utilize this protein's unique properties to explore a remarkable example of biological numerology, whereby nearly every meiotic cell in C. elegans makes precisely six crossovers, one for each of its six chromosome pairs. Copyright © 2012 Elsevier Inc. All rights reserved.

Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial.

PubMed

Kuwata, Hitoshi; Iwasaki, Masahiro; Shimizu, Shinobu; Minami, Kohtaro; Maeda, Haruyo; Seino, Susumu; Nakada, Koji; Nosaka, Chihiro; Murotani, Kenta; Kurose, Takeshi; Seino, Yutaka; Yabe, Daisuke

2016-03-01

Investigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated. The experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n = 10), with age 30-75 years, HbA1c 9.0% (75 mmol/mol) or less, and BMI 35 kg/m(2) or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by (13)C-acetate breath test involving measurement of (13)CO2 in breath samples collected before and after ingestion of rice steamed with (13)C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment. FR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC-15-240 min-glucose: type 2 diabetes, FR 2,326.6 ± 114.7 mmol/l × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 ± 72.3 mmol/l × min, MR 1,389.7 ± 69.4 mmol/l × min, RF 1,483.9 ± 72.8 mmol/l × min) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, FR 1.94 ± 0.22 mmol/l, MR 1.68 ± 0.18 mmol/l, RF 2.77 ± 0.24 mmol/l [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 0.95 ± 0.21 mmol/l, MR 0.83 ± 0.16 mmol/l, RF 1.18 ± 0.27 mmol/l). FR and MR also enhanced GLP-1 secretion, MR more strongly than FR or RF (AUC-15-240 min-GLP-1: type 2 diabetes, FR 7,123.4 ± 376.3 pmol/l × min, MR 7,743.6 ± 801.4 pmol/l × min, RF 6,189.9 ± 581.3 pmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 ± 324.6 pmol/l × min, MR 4,897.7 ± 330.7 pmol/l × min, RF 3,747.5 ± 572.6 pmol/l × min [p < 0.05 for MR vs RF and MR vs FR]). FR and MR delayed gastric emptying (Time50%: type 2 diabetes, FR 83.2 ± 7.2 min, MR 82.3 ± 6.4 min, RF 29.8 ± 3.9 min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 66.3 ± 5.5 min, MR 74.4 ± 7.6 min, RF 32.4 ± 4.5 min [p < 0.05 for FR vs RF and MR vs RF]), which is associated with amelioration of postprandial glucose excursion (AUC-15-120 min-glucose: type 2 diabetes, r = -0.746, p < 0.05; healthy, r = -0.433, p < 0.05) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, r = -0.578, p < 0.05; healthy, r = -0.526, p < 0.05), as well as with increasing GLP-1 (AUC-15-120 min-GLP-1: type 2 diabetes, r = 0.437, p < 0.05; healthy, r = 0.300, p = 0.107) and glucagon (AUC-15-120 min-glucagon: type 2 diabetes, r = 0.399, p < 0.05; healthy, r = 0.471, p < 0.05). The measured outcomes were comparable between the two randomised groups. Meal sequence can play a role in postprandial glucose control through both delayed gastric emptying and enhanced incretin secretion. Our findings provide clues for medical nutrition therapy to better prevent and manage type 2 diabetes. UMIN Clinical Trials Registry UMIN000017434. Japan Society for Promotion of Science, Japan Association for Diabetes Education and Care, and Japan Vascular Disease Research Foundation.

Serotonin enhances the impact of health information on food choice.

PubMed

Vlaev, Ivo; Crockett, Molly J; Clark, Luke; Müller, Ulrich; Robbins, Trevor W

2017-06-01

Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine. Twenty-seven participants attended three sessions and received single doses of atomoxetine, citalopram, and placebo in a double-blind randomised cross-over design. Relative to placebo, citalopram increased choices of more healthy foods over less healthy foods. Citalopram also increased the emphasis on health considerations in decisions. Atomoxetine did not affect decision making relative to placebo. The results support the hypothesis that serotonin may influence food choice by enhancing a focus on long-term goals. The findings are relevant for understanding decisions about food consumption and also for treating health conditions such as eating disorders and obesity.

Dose-dependent heart rate reducing effect of nizatidine, a histamine H2-receptor antagonist.

PubMed Central

Hinrichsen, H; Halabi, A; Fuhrmann, G; Kirch, W

1993-01-01

1. Twelve healthy subjects were treated in a randomised placebo-controlled crossover study with placebo, 150 mg, 300 mg, and 600 mg nizatidine, 100 mg pirenzepine, and 300 mg nizatidine plus 100 mg pirenzepine for 1 week each. 2. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, impedance cardiographic and Doppler ultrasound variables were measured. 3. Stroke volume and blood pressure were not altered by nizatidine and/or pirenzepine. By contrast, heart rate and cardiac output significantly (P < 0.05) decreased in a dose-dependent manner 1.5 and 3 h after administration of 300 and 600 mg nizatidine. Treatment with 150 mg nizatidine led to similar though non-significant trends. 4. While a slightly insignificant rise in heart rate was detected with pirenzepine alone, heart rate and cardiac output remained unchanged upon combined nizatidine and pirenzepine treatment as compared with placebo and baseline values. 5. In conclusion, nizatidine reduced heart rate and cardiac output in a dose-dependent manner, whereas this negative chronotropic effect was counteracted by concurrent administration of the anti-cholinergic drug pirenzepine. PMID:8099802

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial.

PubMed

van Duijn, Pleun Joppe; Verbrugghe, Walter; Jorens, Philippe Germaine; Spöhr, Fabian; Schedler, Dirk; Deja, Maria; Rothbart, Andreas; Annane, Djillali; Lawrence, Christine; Nguyen Van, Jean-Claude; Misset, Benoit; Jereb, Matjaz; Seme, Katja; Šifrer, Franc; Tomiç, Viktorija; Estevez, Francisco; Carneiro, Jandira; Harbarth, Stephan; Eijkemans, Marinus Johannes Cornelis; Bonten, Marc

2018-04-01

Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum β-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837-1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU. European Union Seventh Framework Programme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sustained impact of energy-dense TV and online food advertising on children's dietary intake: a within-subject, randomised, crossover, counter-balanced trial.

PubMed

Norman, Jennifer; Kelly, Bridget; McMahon, Anne-T; Boyland, Emma; Baur, Louise A; Chapman, Kathy; King, Lesley; Hughes, Clare; Bauman, Adrian

2018-04-12

Policies restricting children's exposure to unhealthy food marketing have been impeded by the lack of evidence showing a direct link between food advertising exposure and children's energy intake and body weight. Food advertising exposure increases children's immediate food consumption, but whether this increased intake is compensated for at later eating occasions is not known; consequently the sustained effect on diets remains unclear. We conducted a within-subject, randomised, crossover, counterbalanced study across four, six-day holiday camps in New South Wales, Australia between April 2016 and January 2017. Children (7-12 years, n = 160) were recruited via local schools, email networks and social media. Two gender- and age-balanced groups were formed for each camp (n = 20), randomised to either a multiple- or single- media condition and exposed to food and non-food advertising in an online game and/or a television cartoon. Children's food consumption (kilojoules) was measured at a snack immediately after exposure and then at lunch later in the day. Linear mixed models were conducted to examine relationships between food advertising exposure and dietary intake, taking into account gender, age and weight status. All children in the multiple-media condition ate more at a snack after exposure to food advertising compared with non-food advertising; this was not compensated for at lunch, leading to additional daily food intake of 194 kJ (95% CI 80-308, p = 0.001, d = 0.2). Exposure to multiple-media food advertising compared with a single-media source increased the effect on snack intake by a difference of 182 kJ (95% CI 46-317, p = 0.009, d = 0.4). Food advertising had an increased effect among children with heavier weight status in both media groups. Online ('advergame') advertising combined with TV advertising exerted a stronger influence on children's food consumption than TV advertising alone. The lack of compensation at lunch for children's increased snack intake after food advertising exposure suggests that unhealthy food advertising exposure contributes to a positive energy-gap, which could cumulatively lead to the development of overweight. Australian New Zealand Clinical Trials Registry, number ACTRN12617001230347 (Retrospectively registered).

Effects of a Worksite Weight-Control Programme in Obese Male Workers: A Randomized Controlled Crossover Trial

ERIC Educational Resources Information Center

Iriyama, Yae; Murayama, Nobuko

2014-01-01

Objective: We conducted a randomized controlled crossover trial to evaluate the effects of a new worksite weight-control programme designed for men with or at risk of obesity using a combination of nutrition education and nutrition environmental interventions. Subjects and methods: Male workers with or at risk of obesity were recruited for this…

Vitamin K supplementation for cystic fibrosis.

PubMed

Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

2015-01-18

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 08 October 2014. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

Vitamin K supplementation for cystic fibrosis.

PubMed

Jagannath, Vanitha A; Thaker, Vidhu; Chang, Anne B; Price, Amy I

2017-08-22

Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to.

The effect of transcranial direct current stimulation (tDCS) on locomotion and balance in patients with chronic stroke: study protocol for a randomised controlled trial.

PubMed

Geiger, M; Supiot, A; Zory, R; Aegerter, P; Pradon, D; Roche, N

2017-10-23

Following stroke, patients are often left with hemiparesis that reduces balance and gait capacity. A recent, non-invasive technique, transcranial direct current stimulation, can be used to modify cortical excitability when used in an anodal configuration. It also increases the excitability of spinal neuronal circuits involved in movement in healthy subjects. Many studies in patients with stroke have shown that this technique can improve motor, sensory and cognitive function. For example, anodal tDCS has been shown to improve motor performance of the lower limbs in patients with stroke, such as voluntary quadriceps strength, toe-pinch force and reaction time. Nevertheless, studies of motor function have been limited to simple tasks. Surprisingly, the effects of tDCS on the locomotion and balance of patients with chronic stroke have never been evaluated. In this study, we hypothesise that anodal tDCS will improve balance and gait parameters in patients with chronic stroke-related hemiparesis through its effects at cortical and spinal level. This is a prospective, randomised, placebo-controlled, double-blinded, single-centre, cross-over study over 36 months. Forty patients with chronic stroke will be included. Each patient will participate in three visits: an inclusion visit, and two visits during which they will all undergo either one 30-min session of transcranial direct current stimulation or one 30-min session of placebo stimulation in a randomised order. Evaluations will be carried out before, during and twice after stimulation. The primary outcome is the variability of the displacement of the centre of mass during gait and a static-balance task. Secondary outcomes include clinical and functional measures before and after stimulation. A three-dimensional gait analysis, and evaluation of static balance on a force platform will be also conducted before, during and after stimulation. These results should constitute a useful database to determine the aspects of complex motor function that are the most improved by transcranial direct current stimulation in patients with hemiparesis. It is the first essential step towards validating this technique as a treatment, coupled with task-oriented training. ClinicalTrials.gov, ID: NCT02134158 . First received on 18 December 2013; last updated on 14 September 2016. Other study ID numbers: P120135 / AOM12126, 2013-A00952-43.

Vitamin K supplementation for cystic fibrosis

PubMed Central

Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

2015-01-01

Background Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. Objectives To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 08 October 2014. Selection criteria Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Data collection and analysis Two authors independently screened papers, extracted trial details and assessed their risk of bias. Main results Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a crossover design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Authors’ conclusions Evidence from randomised controlled trials on the benefits of routine vitamin K supplementation for people with CF is currently weak and limited to two small trials of short duration. However, no harm was found and until further evidence is available, the present recommendations should be adhered to. PMID:25879106

Impact of post-meal and one-time daily exercise in patient with type 2 diabetes mellitus: a randomized crossover study.

PubMed

Pahra, Daizy; Sharma, Nitasha; Ghai, Sandhya; Hajela, Abhishek; Bhansali, Shobhit; Bhansali, Anil

2017-01-01

To evaluate the effectiveness of short-timed post-meal and one-time daily exercise on glycemic control in patients with T2DM. Sixty-four T2DM patients were randomised into crossover design. Group A (n = 32) underwent post-meal exercise (moderate-intensity brisk walking covering 1500-1600 steps for 15 min, starting 15 min after each meal) from d1 to d60 followed by one-time daily exercise (45 min pre-breakfast brisk walking at stretch covering 4500-4800 steps) from d61 to d120, while it was vice versa for the group B (n = 32). The five-point blood glucose profile was performed on d1, d30, d60, d90 and d120, and HbA1c on d1, d60 and d120. Fitness wrist band was used for step-counting to ensure the intensity of exercise and compliance to exercise protocol. Group A patients showed a significant improvement in five point blood glucose profile and HbA1c after performing post-meal exercise (p < 0.001), which was mitigated after switchover to one-time daily exercise (p < 0.001). While, group B patients showed improvement in glucose profile and HbA1c (p < 0.001) after performing post-meal exercise, as compared to one-time daily exercise. Further, on pooled analysis (post-meal versus one-time daily exercise group) the beneficial effect of post-meal exercise on glucose profile and HbA1c was consistent as compared to one time daily exercise and the significance persisted on comparison between the two groups. No hypoglycemic events were noted between the groups during the study period. Post-meal exercise is more effective than routine one-time daily exercise for glycemic control in T2DM patients.

Association between bibliometric parameters, reporting and methodological quality of randomised controlled trials in vascular and endovascular surgery.

PubMed

Hajibandeh, Shahab; Hajibandeh, Shahin; Antoniou, George A; Green, Patrick A; Maden, Michelle; Torella, Francesco

2017-04-01

Purpose We aimed to investigate association between bibliometric parameters, reporting and methodological quality of vascular and endovascular surgery randomised controlled trials. Methods The most recent 75 and oldest 75 randomised controlled trials published in leading journals over a 10-year period were identified. The reporting quality was analysed using the CONSORT statement, and methodological quality with the Intercollegiate Guidelines Network checklist. We used exploratory univariate and multivariable linear regression analysis to investigate associations. Findings Bibliometric parameters such as type of journal, study design reported in title, number of pages; external funding, industry sponsoring and number of citations are associated with reporting quality. Moreover, parameters such as type of journal, subject area and study design reported in title are associated with methodological quality. Conclusions The bibliometric parameters of randomised controlled trials may be independent predictors for their reporting and methodological quality. Moreover, the reporting quality of randomised controlled trials is associated with their methodological quality and vice versa.

Fortuitous phenomena: on complexity, pragmatic randomised controlled trials, and knowledge for evidence-based practice.

PubMed

Thompson, Carl

2004-01-01

Many of the interventions that nurses develop and implement are in themselves complex and have to operate in situations of irreducible complexity and uncertainty. This article argues that the primary means of generating knowledge for the evidence-based deployment of complex interventions should be the pragmatic randomised controlled trial. Randomised controlled trials represent the only research design to adequately deal with that which we know and (far more importantly) that which we do not. Using the example of practice development as an exemplar for complexity, and drawing on the objections often voiced as a response to calls to make use of randomised controlled trials in nursing and nursing research, the article presents a developmental framework and some methodological solutions to problems often encountered. Randomised controlled trials, whilst undoubtedly methodologically and strategically challenging, offer the most robust basis for developing primary research knowledge on the effects of complex interventions in nursing and their active components.

Compliance with the CONSORT checklist in obstetric anaesthesia randomised controlled trials.

PubMed

Halpern, S H; Darani, R; Douglas, M J; Wight, W; Yee, J

2004-10-01

The Consolidated Standards for Reporting of Trials (CONSORT) checklist is an evidence-based approach to help improve the quality of reporting randomised controlled trials. The purpose of this study was to determine how closely randomised controlled trials in obstetric anaesthesia adhere to the CONSORT checklist. We retrieved all randomised controlled trials pertaining to the practice of obstetric anaesthesia and summarised in Obstetric Anesthesia Digest between March 2001 and December 2002 and compared the quality of reporting to the CONSORT checklist. The median number of correctly described CONSORT items was 65% (range 36% to 100%). Information pertaining to randomisation, blinding of the assessors, sample size calculation, reliability of measurements and reporting of the analysis were often omitted. It is difficult to determine the value and quality of many obstetric anaesthesia clinical trials because journal editors do not insist that this important information is made available to readers. Both clinicians and clinical researchers would benefit from uniform reporting of randomised trials in a manner that allows rapid data retrieval and easy assessment for relevance and quality.

Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study.

PubMed

Olmedilla-Alonso, B; Granado-Lorencio, F; Herrero-Barbudo, C; Blanco-Navarro, I; Blázquez-García, S; Pérez-Sacristán, B

2008-04-01

Diet and lifestyle are modifiable factors involved in the development and prevention of non-communicable diseases, including cardiovascular disease. Nut consumption, particularly walnut intake, has been inversely related to incident coronary heart disease (CHD) in observational studies and to improved lipid profiles in short-term feeding trials. To assess the potential functional effect associated with the regular consumption of walnut-enriched restructured meat products in subjects at risk for cardiovascular disease (CVD). A crossover single-dose bioavailability study (n = 3) using gamma-tocopherol as exposure marker and a crossover unblinded dietary intervention study (5 weeks) in subjects at risk (n = 25). Dietary intervention consisted of regular consumption of the meat product, with or without walnuts, five times per week for five weeks with a 1-month washout in between. Overnight fasting blood samples were collected on days 0, 12, 21, 28 and 35, coinciding with blood pressure and body weight recordings. Participants were asked to complete a diet record throughout the study. The functional effects were assessed using clinically relevant and related biomarkers of CHD: serum total, HDL and LDL cholesterol, triacylglycerols, homocysteine, vitamins B(6) and B(12), folic acid, alpha-tocopherol and platelet function test (obturation time). The regular consumption of walnut-enriched meat products compared with that of the restructured meat products without added walnuts provokes a decrease in total cholesterol of 6.8 mg/dl (CI(95%): -12.8, -0.85). Compared to baseline (mixed diet), meat products with walnuts decreased total cholesterol (-10.7 mg/dl, CI(95%): -17.1, -4.2), LDL cholesterol (-7.6 mg/dl, CI(95%): -2.2, -13.0) and body weight (-0.5 kg, CI(95%): -0.1, -0.9) and increased gamma-tocopherol (8.9 mg/dl, CI(95%): 1.0, 16.8). The restructured meat products with added walnuts supplied in this study can be considered functional foods for subjects at high risk for CVD, as their regular consumption provokes a reduction in total cholesterol of 4.5% with respect to baseline values (mixed diet) and 3% with respect to the restructured meat without walnuts.

Case-crossover design and its implementation in R

PubMed Central

2016-01-01

Case-crossover design is a variation of case-control design that it employs persons’ history periods as controls. Case-crossover design can be viewed as the hybrid of case-control study and crossover design. Characteristic confounding that is constant within one person can be well controlled with this method. The relative risk and odds ratio, as well as their 95% confidence intervals (CIs), can be estimated using Cochran-Mantel-Haenszel method. R codes for the calculation are provided in the main text. Readers may adapt these codes to their own task. Conditional logistic regression model is another way to estimate odds ratio of the exposure. Furthermore, it allows for incorporation of other time-varying covariates that are not constant within subjects. The model fitting per se is not technically difficult because there is well developed statistical package. However, it is challenging to convert original dataset obtained from case report form to that suitable to be passed to clogit() function. R code for this task is provided and explained in the text. PMID:27761445

A protocol for a systematic review of non-randomised evaluations of strategies to improve participant recruitment to randomised controlled trials.

PubMed

Gardner, Heidi R; Fraser, Cynthia; MacLennan, Graeme; Treweek, Shaun

2016-08-02

Randomised controlled trials guard against selection bias and therefore offer the fairest way of evaluating healthcare interventions such as medicinal products, devices and services. Recruitment to trials can be extremely difficult, and poor recruitment can lead to extensions to both time and budget and may result in an underpowered study which does not satisfactorily answer the original research question. In the worst cases, a trial may be abandoned, causing huge waste. The evidence to support the choice of recruitment interventions is currently weak. Non-randomised evaluations of recruitment interventions are currently rejected on grounds of poor methodological quality, but systematic evaluation and assessment of this substantial body of work (using Grading of Recommendations Assessment, Development and Evaluation (GRADE) where possible) may provide useful information to support and inform the recruitment decisions of trialists and the research priorities of methodology researchers. The following databases will be searched for relevant studies: Cochrane Methodology Register, MEDLINE, EMBASE, CINAHL and PsycINFO. Any non-randomised study that includes a comparison of two or more interventions to improve recruitment to randomised controlled trials will be included. We will not apply any restrictions on publication date, language or journal. The primary outcome will be the number of individuals or centres recruited into a randomised controlled trial. The secondary outcome will be cost per recruit. Two reviewers will independently screen abstracts for eligible studies, and then, full texts of potentially relevant records will be reviewed. Disagreements will be resolved through discussion. The methodological quality of studies will be assessed using the Cochrane risk of bias tool for non-randomised studies, and the GRADE system will be used if studies are pooled. This review aims to summarise the evidence on methods used to improve recruitment to randomised controlled trials. Carrying out a systematic review including only data from non-randomised studies is a novel approach, and one which some may argue is futile. However, we believe that the systematic evaluation of what is likely to be a substantial amount of research activity is necessary, worthwhile, and will yield valuable results for the clinical trials community regardless of whether the outcomes find in favour of one or more interventions. Should the results of this review suggest that non-randomised evaluations do have something to offer trialists planning their recruitment strategies, the review may be combined in the future with the Cochrane review of randomised evaluations to produce a full review of recruitment strategies encompassing both randomised and non-randomised evaluation methods. PROSPERO CRD42016037718.

Functional added value of microprocessor-controlled knee joints in daily life performance of Medicare Functional Classification Level-2 amputees.

PubMed

Theeven, Patrick; Hemmen, Bea; Rings, Frans; Meys, Guido; Brink, Peter; Smeets, Rob; Seelen, Henk

2011-10-01

To assess the effects of using a microprocessor-controlled prosthetic knee joint on the functional performance of activities of daily living in persons with an above-knee leg amputation. To assess the effects of using a microprocessor-controlled prosthetic knee joint on the functional performance of activities of daily living in persons with an above-knee leg amputation. Randomised cross-over trial. Forty-one persons with unilateral above-knee or knee disarticulation limb loss, classified as Medicare Functional Classification Level-2 (MFCL-2). Participants were measured in 3 conditions, i.e. using a mechanically controlled knee joint and two types of microprocessor-controlled prosthetic knee joints. Functional performance level was assessed using a test in which participants performed 17 simulated activities of daily living (Assessment of Daily Activity Performance in Transfemoral amputees test). Performance time was measured and self-perceived level of difficulty was scored on a visual analogue scale for each activity. High levels of within-group variability in functional performance obscured detection of any effects of using a microprocessor-controlled prosthetic knee joint. Data analysis after stratification of the participants into 3 subgroups, i.e. participants with a "low", "intermediate" and "high" functional mobility level, showed that the two higher functional subgroups performed significantly faster using microprocessor-controlled prosthetic knee joints. MFCL-2 amputees constitute a heterogeneous patient group with large variation in functional performance levels. A substantial part of this group seems to benefit from using a microprocessor-controlled prosthetic knee joint when performing activities of daily living.

Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial.

PubMed

Montes, B; Catalan, M; Roces, A; Jeanniot, J P; Honorato, J M

1993-01-01

The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml.min-1, and its apparent volume of distribution was moderately large (215 l). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng.ml-1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.

Randomised Controlled Trials in Education Research: A Case Study of an Individually Randomised Pragmatic Trial

ERIC Educational Resources Information Center

Torgerson, Carole J.

2009-01-01

The randomised controlled trial (RCT) is an evaluative method used by social scientists in order to establish whether or not an intervention is effective. This contribution discusses the fundamental aspects of good RCT design. These are illustrated through the use of a recently completed RCT which evaluated an information and communication…

Sleep positioning systems for children with cerebral palsy.

PubMed

Blake, Sharon F; Logan, Stuart; Humphreys, Ginny; Matthews, Justin; Rogers, Morwenna; Thompson-Coon, Joanna; Wyatt, Katrina; Morris, Christopher

2015-01-01

Sleep positioning systems can be prescribed for children with cerebral palsy to help reduce or prevent hip migration, provide comfort to ease pain and/or improve sleep. As sleep disturbance is common in children with developmental disabilities, with impact on their carers' sleep, and as sleep positioning systems can be expensive, guidance is needed to support decisions as to their use. To determine whether commercially-available sleep positioning systems, compared with usual care, reduce or prevent hip migration in children with cerebral palsy. Any negative effect of sleep positioning systems on hip migration will be considered within this objective.Secondary objectives were to determine the effect of sleep positioning systems on: (1) number or frequency of hip problems; (2) sleep patterns and quality; (3) quality of life of the child and family; (4) pain; and (5) physical functioning. We also sought to identify any adverse effects from using sleep positioning systems. In December 2014, we searched CENTRAL, Ovid MEDLINE, Embase, and 13 other databases. We also searched two trials registers. We applied no restrictions on date of publication, language, publication status or study design. We checked references and contacted manufacturers and authors for potentially relevant literature, and searched the internet using Google. We included all randomised controlled trials (RCTs) evaluating whole body sleep positioning systems for children and adolescents (up to 18 years of age) with cerebral palsy. Two review authors independently screened reports retrieved from the search against pre-determined inclusion criteria and assessed the quality of eligible studies.Members of the public (parent carers of children with neurodisability) contributed to this review by suggesting the topic, refining the research objectives, interpreting the findings, and reviewing the plain language summary. We did not identify any randomised controlled trials that evaluated the effectiveness of sleep positioning systems on hip migration.We did find two randomised cross-over trials that met the inclusion criteria in respect of secondary objectives relating to sleep quality and pain. Neither study reported any important difference between sleeping in sleep positioning systems and not for sleep patterns or sleep quality (two studies, 21 children, very low quality evidence) and pain (one study, 11 children, very low quality evidence). These were small studies with established users of sleep positioning systems and were judged to have high risk of bias.We found no eligible trials that explored the other secondary objectives (number or frequency of hip problems, quality of life of the child and family, physical functioning, and adverse effects). We found no randomised trials that evaluated the effectiveness of sleep positioning systems to reduce or prevent hip migration in children with cerebral palsy. Nor did we find any randomised trials that evaluated the effect of sleep positioning systems on the number or frequency of hip problems, quality of life of the child and family or on physical functioning.Limited data from two randomised trials, which evaluated the effectiveness of sleep positioning systems on sleep quality and pain for children with cerebral palsy, showed no significant differences in these aspects of health when children were using and not using a sleep positioning system.In order to inform clinical decision-making and the prescription of sleep positioning systems, more rigorous research is needed to determine effectiveness, cost-effectiveness, and the likelihood of adverse effects.

Relation between burden of disease and randomised evidence in sub-Saharan Africa: survey of research.

PubMed

Isaakidis, Petros; Swingler, George H; Pienaar, Elizabeth; Volmink, Jimmy; Ioannidis, John P A

2002-03-23

To evaluate whether the amount of randomised clinical research on various medical conditions is related to the burden of disease and health needs of the local populations in sub-Saharan Africa. Construction and analysis of comprehensive database of randomised controlled trials in sub-Saharan Africa based on Medline, the Cochrane Controlled Trials Register, and several African databases. Sub-Saharan Africa. Number of trials and randomised subjects for each category of disease in the global burden of disease taxonomy; ratios of disability adjusted life years (DALYs) per amount of randomised evidence. 1179 eligible randomised controlled trials were identified. The number of trials published each year increased over time. Almost half of the trials (n=565) had been done in South Africa. There was relatively good correlation between the estimated burden of disease at year 2000 and the number of trials performed (r=0.53, P=0.024) and the number of participants randomised (r=0.68, P=0.002). However,some conditions-for example, injuries (over 20 000 DALYs per patient ever randomised)-were more neglected than others. Despite recent improvements, few clinical trials are done in sub-Saharan Africa. Clinical research in this part of the world should focus more evenly on the major contributors to burden of disease.

No difference in acute effects of supplemental v. dietary calcium on blood pressure and microvascular function in obese women challenged with a high-fat meal: a cross-over randomised study.

PubMed

Ferreira, Thaís da Silva; Leal, Priscila Mansur; Antunes, Vanessa Parada; Sanjuliani, Antonio Felipe; Klein, Márcia Regina Simas Torres

2016-11-01

Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

Single oral doses of netazepide (YF476), a gastrin receptor antagonist, cause dose-dependent, sustained increases in gastric pH compared with placebo and ranitidine in healthy subjects.

PubMed

Boyce, M; David, O; Darwin, K; Mitchell, T; Johnston, A; Warrington, S

2012-07-01

Nonclinical studies have shown netazepide (YF476) to be a potent, selective, competitive and orally active gastrin receptor antagonist. To administer to humans for the first time single oral doses of netazepide, to assess their tolerability, safety, pharmacokinetics and effect on 24-h gastric pH. We did two randomised double-blind single-dose studies in healthy subjects. The first (n = 12) was a six-way incomplete crossover pilot study of rising doses of netazepide (range 0.5-100 mg) and placebo. The second (n = 20) was a five-way complete crossover study of netazepide 5, 25 and 100 mg, ranitidine 150 mg and placebo. In both trials we collected frequent blood samples, measured plasma netazepide and calculated pharmacokinetic parameters. In the comparative trial we measured gastric pH continuously for 24 h and compared treatments by percentage time gastric pH ≥4. Netazepide was well tolerated. Median t (max) and t (½) for the 100 mg dose were about 1 and 7 h, respectively, and the pharmacokinetics were dose-proportional. Netazepide and ranitidine each increased gastric pH. Onset of activity was similarly rapid for both. All netazepide doses were more effective than placebo (P ≤ 0.023). Compared with ranitidine, netazepide 5 mg was as effective, and netazepide 25 and 100 mg were much more effective (P ≤ 0.010), over the 24 h after dosing. Activity of ranitidine lasted about 12 h, whereas that of netazepide exceeded 24 h. In human: netazepide is an orally active gastrin antagonist, and gastrin has a major role in controlling gastric acidity. Repeated-dose studies are justified. NCT01538784 and NCT01538797. © 2012 Blackwell Publishing Ltd.

[Pre-randomisation in study designs: getting past the taboo].

PubMed

Schellings, R; Kessels, A G; Sturmans, F

2008-09-20

In October 2006 the Dutch Ministry of Health, Welfare and Sport announced that the use of pre-randomisation in study designs is admissible and not in conflict with the Dutch Medical Research in Human Subjects Act. With pre-randomisation, the conventional sequence of obtaining informed consent followed by randomisation is reversed. According to the original pre-randomisation design (Zelen design), participants are randomised before they are asked to consent; after randomisation, only participants in the experimental group are asked to consent to treatment and effect measurement. In the past, pre-randomisation has seldom been used, and when it was, it was often under the wrong circumstances. Awareness regarding the ethical, legal and methodological objections to pre-randomisation is increasing. About a decade ago, we illustrated the applicability and acceptability of pre-randomisation by means of a fictitious heroin provision trial. In general, pre-randomisation is justified if valid evaluation of the effects of an intervention is impossible using a conventional randomised design, e.g., if knowledge of the intervention may lead to non-compliance or drop-out in the control group, or when the intervention is an educational programme. Other requirements for pre-randomisation include the following: the study has a clinically relevant objective, it is likely that the study will lead to important new insights, the informed consent procedure bears no potential harm to participants, at least standard care is offered to participants in the control group, and the approval of an independent research ethics committee is obtained.

X-Chromosome Control of Genome-Scale Recombination Rates in House Mice.

PubMed

Dumont, Beth L

2017-04-01

Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus , were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females. Copyright © 2017 by the Genetics Society of America.

Use of 0.1% chlorine dioxide to inhibit the formation of morning volatile sulphur compounds (VSC).

PubMed

Peruzzo, Daiane Cristina; Jandiroba, Priscila Fontoura Castelo Branco; Nogueira Filho, Getulio da Rocha

2007-01-01

The aim of this study was to evaluate the VSC-inhibiting effect of a commercially available mouthrinse (0.1% chlorine dioxide) when compared to its placebo. A 2-step double blind, crossover, randomised study was conducted with 14 dental students with healthy periodontium, who refrained from any mechanical plaque and tongue coating control during two 4-day experimental periods. The subjects were instructed to rinse 3 times daily with the assigned product during each period. A 7-day washout interval was established. VSCs levels were measured by a sulphide monitor at the beginning (baseline) and at the end of each experimental period. Statistical analyses were performed using Wilcoxon's and Mann-Whitney's non-parametric tests. At baseline, intragroup analysis revealed that VSCs levels did not differ between groups (p > 0.05); at day 5, the use of the chlorine dioxide mouthrinse did not change the baseline VSCs scores in the control group (p > 0.05), while a 2-fold increase was observed with the use of the placebo mouthrinse (p < 0.05). Intergroup analysis showed a significant difference between the VSCs levels of the test and control groups (40.2 +/- 30.72 and 82.3 +/- 75.63 ppb, p < 0.001) at day 5. Within the limits of this study, the findings suggest that a mouthrinse containing chlorine dioxide can maintain VSCs at lower levels in the morning breath.

Neurokinin B administration induces hot flushes in women.

PubMed

Jayasena, Channa N; Comninos, Alexander N; Stefanopoulou, Evgenia; Buckley, Adam; Narayanaswamy, Shakunthala; Izzi-Engbeaya, Chioma; Abbara, Ali; Ratnasabapathy, Risheka; Mogford, Julianne; Ng, Noel; Sarang, Zubair; Ghatei, Mohammad A; Bloom, Stephen R; Hunter, Myra S; Dhillo, Waljit S

2015-02-16

Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes. However, the effects of NKB administration on hot flushes have not been investigated in humans. To address this, we performed a randomised, double-blinded, placebo-controlled, 2-way cross-over study. Ten healthy women were admitted to a temperature and humidity-controlled research unit. Participants received 30 minute intravenous infusions of NKB and vehicle in random order. Symptoms, heart rate, blood pressure, sweating and skin temperature were compared between NKB and vehicle in a double-blinded manner. Eight of ten participants experienced flushing during NKB infusion with none experiencing flushing during vehicle infusion (P = 0.0007). Significant elevations in heart rate (P = 0.0106 vs. pre-symptoms), and skin temperature measured using skin probe (P = 0.0258 vs. pre-symptoms) and thermal imaging (P = 0.0491 vs. pre-symptoms) characteristic of menopausal flushing were observed during hot flush episodes. Our findings provide evidence that NKB administration can cause hot flushes in women. Further studies are required to determine if pharmacological blockade of NKB signalling could inhibit hot flushes during the menopause and during treatment for sex-steroid dependent cancers.

Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial.

PubMed

Wechsler, Michael E; Kunselman, Susan J; Chinchilli, Vernon M; Bleecker, Eugene; Boushey, Homer A; Calhoun, William J; Ameredes, Bill T; Castro, Mario; Craig, Timothy J; Denlinger, Loren; Fahy, John V; Jarjour, Nizar; Kazani, Shamsah; Kim, Sophia; Kraft, Monica; Lazarus, Stephen C; Lemanske, Robert F; Markezich, Amy; Martin, Richard J; Permaul, Perdita; Peters, Stephen P; Ramsdell, Joe; Sorkness, Christine A; Sutherland, E Rand; Szefler, Stanley J; Walter, Michael J; Wasserman, Stephen I; Israel, Elliot

2009-11-21

Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid. In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype. Individuals in a matched pair were randomly assigned by computer-generated randomisation sequence to receive inhaled longacting beta2 agonist (salmeterol 50 microg twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 microg twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00200967. After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21.4 L/min (95% CI 11.8-31.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). In Gly/Gly participants, morning PEF was 21.5 L/min (11.0-32.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p<0.0001). The improvement in PEF did not differ between genotypes (difference [Arg/Arg-Gly/Gly] -0.1, -14.4 to 14.2; p=0.99). In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a prespecified secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p<0.0001). Responsiveness to methacholine did not differ between salmeterol and placebo in Arg/Arg participants (p=0.87). The 2.5 times higher genotype-specific difference in responsiveness to methacholine was significant (1.32 doubling dose difference between genotypes, 0.43-2.21, p=0.0038). Seven Arg/Arg participants (placebo, n=5; salmeterol, n=2) and six Gly/Gly participants (placebo, n=3; salmeterol, n=3) had an asthma exacerbation. Five serious adverse events were reported, one each during the pre-match and run-in phases on open-label inhaled corticosteroid, two during double-blind treatment with salmeterol/inhaled corticosteroid, and one during double-blind treatment with placebo/inhaled corticosteroid. None of the serious events was asthma-related or related to study drugs or procedures. In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. These findings suggest that patients should continue to be treated with longacting beta2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. Further investigation is needed to establish the importance of the genotype-specific difference in responsiveness to methacholine. National Institutes of Health.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.

PubMed

Cooper, Cindy L; Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-04-01

External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

PubMed Central

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

Evaluation of the anti-fatigue effects of a traditional herbal drug, Gongjin-dan, under insufficient sleep conditions: study protocol for a randomised controlled trial.

PubMed

Son, Mi Ju; Im, Hwi-Jin; Kim, Young-Eun; Ku, Boncho; Lee, Jun-Hwan; Son, Chang-Gue

2016-08-22

Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans. To investigate the anti-fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress-related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase. This study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue. Korean National Clinical Trial Registry CRIS; KCT0001681 , registered on 29 October 2015.

The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT interval in a thorough QT (TQT) study

PubMed Central

2013-01-01

Background Empagliflozin is a potent, selective sodium glucose cotransporter 2 (SGLT2) inhibitor in development as an oral antidiabetic treatment. This QT interval study assessed potential effects of empagliflozin on ventricular repolarisation and other electrocardiogram (ECG) parameters. Methods A randomised, placebo-controlled, single-dose, double-blind, five-period crossover study incorporating a novel double-placebo period design to reduce sample size, while maintaining full statistical power. Treatments: single empagliflozin doses of 25 mg (therapeutic) and 200 mg (supratherapeutic), matching placebo and open-label moxifloxacin 400 mg (positive control). Triplicate 12-lead ECGs of 10 second duration were recorded at baseline and during the first 24 hours after dosing. The primary endpoint was mean change from baseline (MCfB) in the population heart rate-corrected QT interval (QTcN) between 1–4 hours after dosing. Results Thirty volunteers (16 male, 14 female, mean [range] age: 34.5 [18–52] years) were randomised. The placebo-corrected MCfB in QTcN 1–4 hours after dosing was 0.6 (90% CI: -0.7, 1.9) ms and -0.2 (-1.4, 0.9) ms for empagliflozin 25 mg and 200 mg, respectively, below the ICH E14 defined threshold of regulatory concern 10 ms. Assay sensitivity was confirmed by a placebo-corrected MCfB in QTcN 2–4 hours post-dose of 12.4 (10.7, 14.1) ms with moxifloxacin 400 mg. Empagliflozin tolerability was good for all volunteers; 23.3% experienced adverse events (AEs) with empagliflozin and 27.6% with placebo. The most frequent AE was nasopharyngitis. Conclusions/interpretation Single doses of empagliflozin 25 mg and 200 mg were not associated with QTcN prolongation and were well tolerated in healthy volunteers. Trial registration ClinicalTrials.gov: NCT01195675 PMID:23617452

Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

PubMed Central

Sonestedt, Emily; Øverby, Nina Cecilie; Laaksonen, David E.; Birgisdottir, Bryndis Eva

2012-01-01

Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose) on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers), and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies), four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies were available to draw conclusions. PMID:22855643

Health promotion interventions for community-dwelling older people with mild or pre-frailty: a systematic review and meta-analysis.

PubMed

Frost, Rachael; Belk, Celia; Jovicic, Ana; Ricciardi, Federico; Kharicha, Kalpa; Gardner, Benjamin; Iliffe, Steve; Goodman, Claire; Manthorpe, Jill; Drennan, Vari M; Walters, Kate

2017-07-20

Mild or pre-frailty is common and associated with increased risks of hospitalisation, functional decline, moves to long-term care, and death. Little is known about the effectiveness of health promotion in reducing these risks. This systematic review aimed to synthesise randomised controlled trials (RCTs) evaluating home and community-based health promotion interventions for older people with mild/pre-frailty. We searched 20 bibliographic databases and 3 trials registers (January 1990 - May 2016) using mild/pre-frailty and associated terms. We included randomised controlled and crossover trials of health promotion interventions for community-dwelling older people (65+ years) with mild/pre-frailty and excluded studies focussing on populations in hospital, long term care facilities or with a specific condition. Risk of bias was assessed by two reviewers using the Cochrane Risk of Bias tool. We pooled study results using standardised mean differences (SMD) where possible and used narrative synthesis where insufficient outcome data were available. We included 10 articles reporting on seven trials (total n = 506 participants) and included five trials in a meta-analysis. Studies were predominantly small, of limited quality and six studies tested group exercise alone. One study additionally investigated a nutrition and exercise intervention and one evaluated telemonitoring. Interventions of exercise in groups showed mixed effects on functioning (no effects on self-reported functioning SMD 0.19 (95% CI -0.57 to 0.95) n = 3 studies; positive effects on performance-based functioning SMD 0.37 (95% CI 0.07 to 0.68) n = 3 studies). No studies assessed moves to long-term care or hospitalisations. Currently the evidence base is of insufficient size, quality and breadth to recommend specific health promotion interventions for older people with mild or pre- frailty. High quality studies of rigorously developed interventions are needed. CRD42014010370 (Review 2).

A causal model for longitudinal randomised trials with time-dependent non-compliance

PubMed Central

Becque, Taeko; White, Ian R; Haggard, Mark

2015-01-01

In the presence of non-compliance, conventional analysis by intention-to-treat provides an unbiased comparison of treatment policies but typically under-estimates treatment efficacy. With all-or-nothing compliance, efficacy may be specified as the complier-average causal effect (CACE), where compliers are those who receive intervention if and only if randomised to it. We extend the CACE approach to model longitudinal data with time-dependent non-compliance, focusing on the situation in which those randomised to control may receive treatment and allowing treatment effects to vary arbitrarily over time. Defining compliance type to be the time of surgical intervention if randomised to control, so that compliers are patients who would not have received treatment at all if they had been randomised to control, we construct a causal model for the multivariate outcome conditional on compliance type and randomised arm. This model is applied to the trial of alternative regimens for glue ear treatment evaluating surgical interventions in childhood ear disease, where outcomes are measured over five time points, and receipt of surgical intervention in the control arm may occur at any time. We fit the models using Markov chain Monte Carlo methods to obtain estimates of the CACE at successive times after receiving the intervention. In this trial, over a half of those randomised to control eventually receive intervention. We find that surgery is more beneficial than control at 6months, with a small but non-significant beneficial effect at 12months. © 2015 The Authors. Statistics in Medicine Published by JohnWiley & Sons Ltd. PMID:25778798

Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study.

PubMed

Alda, Martin; McKinnon, Margaret; Blagdon, Ryan; Garnham, Julie; MacLellan, Susan; O'Donovan, Claire; Hajek, Tomas; Nair, Cynthia; Dursun, Serdar; MacQueen, Glenda

2017-01-01

Residual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects. We conducted a double-blind crossover study of a low dose (15 mg, 'placebo') and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine. Thirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning. The active dose of methylene blue significantly improved symptoms of depression both on the Montgomery-Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects. Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder. © The Royal College of Psychiatrists 2017.

Effect of almond consumption on vascular function in patients with coronary artery disease: a randomized, controlled, cross-over trial

USDA-ARS?s Scientific Manuscript database

Objective: Almonds reduce cardiovascular disease risk via cholesterol reduction, anti-inflammation, glucoregulation, and antioxidation. The objective of this randomized, controlled, cross-over trial was to determine whether the addition of 85 g almonds daily to a National Cholesterol Education Progr...

A compartmentalized signaling network mediates crossover control in meiosis

PubMed Central

Zhang, Liangyu; Köhler, Simone; Rillo-Bohn, Regina

2018-01-01

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation. PMID:29521627

Prostate cancer - evidence of exercise and nutrition trial (PrEvENT): study protocol for a randomised controlled feasibility trial.

PubMed

Hackshaw-McGeagh, Lucy; Lane, J Athene; Persad, Raj; Gillatt, David; Holly, Jeff M P; Koupparis, Anthony; Rowe, Edward; Johnston, Lyndsey; Cloete, Jenny; Shiridzinomwa, Constance; Abrams, Paul; Penfold, Chris M; Bahl, Amit; Oxley, Jon; Perks, Claire M; Martin, Richard

2016-03-07

A growing body of observational evidence suggests that nutritional and physical activity interventions are associated with beneficial outcomes for men with prostate cancer, including brisk walking, lycopene intake, increased fruit and vegetable intake and reduced dairy consumption. However, randomised controlled trial data are limited. The 'Prostate Cancer: Evidence of Exercise and Nutrition Trial' investigates the feasibility of recruiting and randomising men diagnosed with localised prostate cancer and eligible for radical prostatectomy to interventions that modify nutrition and physical activity. The primary outcomes are randomisation rates and adherence to the interventions at 6 months following randomisation. The secondary outcomes are intervention tolerability, trial retention, change in prostate specific antigen level, change in diet, change in general physical activity levels, insulin-like growth factor levels, and a range of related outcomes, including quality of life measures. The trial is factorial, randomising men to both a physical activity (brisk walking or control) and nutritional (lycopene supplementation or increased fruit and vegetables with reduced dairy consumption or control) intervention. The trial has two phases: men are enrolled into a cohort study prior to radical prostatectomy, and then consented after radical prostatectomy into a randomised controlled trial. Data are collected at four time points (cohort baseline, true trial baseline and 3 and 6 months post-randomisation). The Prostate Cancer: Evidence of Exercise and Nutrition Trial aims to determine whether men with localised prostate cancer who are scheduled for radical prostatectomy can be recruited into a cohort and subsequently randomised to a 6-month nutrition and physical activity intervention trial. If successful, this feasibility trial will inform a larger trial to investigate whether this population will gain clinical benefit from long-term nutritional and physical activity interventions post-surgery. Prostate Cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) is registered on the ISRCTN registry, ref number ISRCTN99048944. Date of registration 17 November 2014.

Coenzyme Q10 for heart failure.

PubMed

Madmani, Mohammed E; Yusuf Solaiman, Ahmad; Tamr Agha, Khalil; Madmani, Yasser; Shahrour, Yasser; Essali, Adib; Kadro, Waleed

2014-06-02

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in patients with heart failure and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels and preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted. To review the safety and efficacy of coenzyme Q10 in heart failure. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase. Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review Manager 5.2 for analysis. We assessed study risk of bias using the Cochrane 'Risk of bias' tool. For dichotomous data, we calculated the risk ratio and for continuous data the mean difference (MD). Where appropriate data were available, we performed meta-analysis. For this review we prioritised data from pooled analyses only. Where meta-analysis was not possible, we wrote a narrative synthesis. We provided a QUOROM flow chart to show the flow of papers. We included seven studies with 914 participants comparing conenzyme Q10 versus placebo. There were no data on clinical events from published randomised trials. The included studies had small sample sizes. Meta-analysis was only possible for a few physiological measures and there was substantial heterogeneity.Only one study reported on total mortality, major cardiovascular events and hospitalisation. Five trials reported on the New York Heart Association (NYHA) classification of clinical status, but it was impossible to pool data due to heterogeneity. None of the included trials considered quality of life, exercise variables, adverse events or cost-effectiveness as outcome measures. Pooled analysis suggests that the use of coenzyme Q10 has no clear effect on left ventricular ejection fraction (MD -2.26; 95% confidence interval (CI) -15.49 to 10.97, n = 60) or exercise capacity (MD 12.79; 95% CI -140.12 to 165.70, n = 85). Pooled data did indicate that supplementation increased blood levels of coenzyme Q10 (MD 1.46; 95% CI 1.19 to 1.72, n = 112). However, there are only a small number of small studies with a risk of bias, so these results should be interpreted with caution. No conclusions can be drawn on the benefits or harms of coenzyme Q10 in heart failure at this time as trials published to date lack information on clinically relevant endpoints. Furthermore, the existing data are derived from small, heterogeneous trials that concentrate on physiological measures: their results are inconclusive. Until further evidence emerges to support the use of coenzyme Q10 in heart failure, there might be a need to re-evaluate whether further trials testing coenzyme Q10 in heart failure are desirable.

Antiplaque Effect of Essential Oils and 0.2% Chlorhexidine on an In Situ Model of Oral Biofilm Growth: A Randomised Clinical Trial

PubMed Central

Tomás, Inmaculada

2015-01-01

Objective To evaluate the in situ antiplaque effect after 4 days of using of 2 commercial antimicrobial agents in short term on undisturbed plaque-like biofilm. Trial Design and Participants An observer-masked, crossover randomised clinical trial on 15 oral and systemically healthy volunteers between 20–30 years who were randomly and sequentially allocated in the same group which performed 3 interventions in different randomised sequences. Intervention The participants wore an appliance in 3 different rinsing periods doing mouthwashes twice a day (1/0/1) with essential oils, 0.2% chlorhexidine or sterile water (negative control). At the end of each 4-day mouthwash period, samples were removed from the appliance. Posteriorly, after bacterial vital staining, samples were analysed using a Confocal Laser Scanning Microscope. Main Outcome Measures Bacterial vitality, thickness and covering grade by the biofilm after 4 days of applying each of the mouthwashes. Results The essential oils and the 0.2% chlorhexidine were significantly more effective than the sterile water at reducing bacterial vitality, thickness and covering grade by the biofilm. No significant differences were found between the 0.2% chlorhexidine and the essential oils at reducing the bacterial vitality (13.2% vs. 14.7%). However, the 0.2% chlorhexidine showed more reduction than the essential oils in thickness (6.5 μm vs. 10.0 μm; p<0.05) and covering grade by the biofilm (20.0% vs. 54.3%; p<0.001). Conclusion The essential oils and 0.2% chlorhexidine showed a high antiplaque effect. Although the 0.2% chlorhexidine showed better results with regard to reducing the thickness and covering grade by the biofilm, both antiseptics showed a high and similar antibacterial activity. Clinical Relevance Daily essential oils or 0.2% chlorhexidine mouthwashes are effective when reducing dental plaque formation in the short term. Although 0.2% chlorhexidine continues to be the “gold standard” in terms of antiplaque effect, essential oils could be considered a reliable alternative. Trial Registration ClinicalTrials.gov NCT02124655 PMID:25689859

Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis

PubMed Central

Wilson, Amie; Gallos, Ioannis D; Plana, Nieves; Lissauer, David; Khan, Khalid S; Zamora, Javier; MacArthur, Christine

2011-01-01

Objective To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. Design Systematic review with meta-analysis. Data sources Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were “birth attend*”, “traditional midwife”, “lay birth attendant”, “dais”, and “comadronas”. Review methods We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. Results We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). Conclusion Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants. PMID:22134967

Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis.

PubMed

Wilson, Amie; Gallos, Ioannis D; Plana, Nieves; Lissauer, David; Khan, Khalid S; Zamora, Javier; MacArthur, Christine; Coomarasamy, Arri

2011-12-01

To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. Systematic review with meta-analysis. Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were "birth attend*", "traditional midwife", "lay birth attendant", "dais", and "comadronas". Review methods We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P<0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P<0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p<0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P<0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants.

Multicentre randomised double bind crossover trial on contamination of conventional ties and bow ties in routine obstetric and gynaecological practice.

PubMed Central

Biljan, M M; Hart, C A; Sunderland, D; Manasse, P R; Kingsland, C R

1993-01-01

OBJECTIVE--To assess level of contamination of neckwear worn by gynaecologists and obstetricians during routine working week. DESIGN--Multicentre randomised double blind crossover trial. Participants wore the same conventional ties for three days in one week and bow ties for the same period in second week. SETTING--Two teaching and three district general hospitals in the midlands, Wales, and north England. SUBJECTS--15 registrars and senior registrars. INTERVENTIONS--A swab soaked in sterile saline was taken from specific area on ties at end of first and third working days and sent in transport medium for culture on chocolatised blood and MacConkey agar for 48 hours. MAIN OUTCOME MEASURES--Level of bacteriological growth assessed semiquantitatively (0 for no contamination; for heavy contamination) after swabs had been cultured. At end of study the participants completed a questionnaire to assess their attitude toward wearing different types of necktie. RESULTS--12 doctors (80%) completed the study. Although bow ties were significantly less contaminated at end of first working day (z = -2.354, p = 0.019), this difference was not maintained; there was no difference in level of contamination on third day. Level of contamination did not increase between first and third day of wearing the same garment. One of the 10 doctors who returned the questionnaire found the bow tie very uncomfortable. All participants would consider wearing a bow tie if it proved to be less contaminated than a conventional tie. CONCLUSIONS--Although a significant difference in contamination was established between conventional and bow ties on first day of study, this difference was not confirmed on third day and there is unlikely to be any real association between tie type and bacterial contamination. Because of its negative image and difficulty to tie, the bow tie will probably remain a minority fashion. Images p1583-a PMID:8292945

Computer classes and games in virtual reality environment to reduce loneliness among students of an elderly reference center: Study protocol for a randomised cross-over design.

PubMed

Antunes, Thaiany Pedrozo Campos; Oliveira, Acary Souza Bulle de; Crocetta, Tania Brusque; Antão, Jennifer Yohanna Ferreira de Lima; Barbosa, Renata Thais de Almeida; Guarnieri, Regiani; Massetti, Thais; Monteiro, Carlos Bandeira de Mello; Abreu, Luiz Carlos de

2017-03-01

Physical and mental changes associated with aging commonly lead to a decrease in communication capacity, reducing social interactions and increasing loneliness. Computer classes for older adults make significant contributions to social and cognitive aspects of aging. Games in a virtual reality (VR) environment stimulate the practice of communicative and cognitive skills and might also bring benefits to older adults. Furthermore, it might help to initiate their contact to the modern technology. The purpose of this study protocol is to evaluate the effects of practicing VR games during computer classes on the level of loneliness of students of an elderly reference center. This study will be a prospective longitudinal study with a randomised cross-over design, with subjects aged 50 years and older, of both genders, spontaneously enrolled in computer classes for beginners. Data collection will be done in 3 moments: moment 0 (T0) - at baseline; moment 1 (T1) - after 8 typical computer classes; and moment 2 (T2) - after 8 computer classes which include 15 minutes for practicing games in VR environment. A characterization questionnaire, the short version of the Short Social and Emotional Loneliness Scale for Adults (SELSA-S) and 3 games with VR (Random, MoviLetrando, and Reaction Time) will be used. For the intervention phase 4 other games will be used: Coincident Timing, Motor Skill Analyser, Labyrinth, and Fitts. The statistical analysis will compare the evolution in loneliness perception, performance, and reaction time during the practice of the games between the 3 moments of data collection. Performance and reaction time during the practice of the games will also be correlated to the loneliness perception. The protocol is approved by the host institution's ethics committee under the number 52305215.3.0000.0082. Results will be disseminated via peer-reviewed journal articles and conferences. This clinical trial is registered at ClinicalTrials.gov identifier: NCT02798081.

Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.

PubMed

Roager, Henrik Munch; Vogt, Josef K; Kristensen, Mette; Hansen, Lea Benedicte S; Ibrügger, Sabine; Mærkedahl, Rasmus B; Bahl, Martin Iain; Lind, Mads Vendelbo; Nielsen, Rikke L; Frøkiær, Hanne; Gøbel, Rikke Juul; Landberg, Rikard; Ross, Alastair B; Brix, Susanne; Holck, Jesper; Meyer, Anne S; Sparholt, Morten H; Christensen, Anders F; Carvalho, Vera; Hartmann, Bolette; Holst, Jens Juul; Rumessen, Jüri Johannes; Linneberg, Allan; Sicheritz-Pontén, Thomas; Dalgaard, Marlene D; Blennow, Andreas; Frandsen, Henrik Lauritz; Villas-Bôas, Silas; Kristiansen, Karsten; Vestergaard, Henrik; Hansen, Torben; Ekstrøm, Claus T; Ritz, Christian; Nielsen, Henrik Bjørn; Pedersen, Oluf Borbye; Gupta, Ramneek; Lauritzen, Lotte; Licht, Tine Rask

2017-11-01

To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. NCT01731366; 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.

Effects of Arabinoxylan and Resistant Starch on Intestinal Microbiota and Short-Chain Fatty Acids in Subjects with Metabolic Syndrome: A Randomised Crossover Study.

PubMed

Hald, Stine; Schioldan, Anne Grethe; Moore, Mary E; Dige, Anders; Lærke, Helle Nygaard; Agnholt, Jørgen; Bach Knudsen, Knud Erik; Hermansen, Kjeld; Marco, Maria L; Gregersen, Søren; Dahlerup, Jens F

2016-01-01

Recently, the intestinal microbiota has been emphasised as an important contributor to the development of metabolic syndrome. Dietary fibre may exert beneficial effects through modulation of the intestinal microbiota and metabolic end products. We investigated the effects of a diet enriched with two different dietary fibres, arabinoxylan and resistant starch type 2, on the gut microbiome and faecal short-chain fatty acids. Nineteen adults with metabolic syndrome completed this randomised crossover study with two 4-week interventions of a diet enriched with arabinoxylan and resistant starch and a low-fibre Western-style diet. Faecal samples were collected before and at the end of the interventions for fermentative end-product analysis and 16S ribosomal RNA bacterial gene amplification for identification of bacterial taxa. Faecal carbohydrate residues were used to verify compliance. The diet enriched with arabinoxylan and resistant starch resulted in significant reductions in the total species diversity of the faecal-associated intestinal microbiota but also increased the heterogeneity of bacterial communities both between and within subjects. The proportion of Bifidobacterium was increased by arabinoxylan and resistant starch consumption (P<0.001), whereas the proportions of certain bacterial genera associated with dysbiotic intestinal communities were reduced. Furthermore, the total short-chain fatty acids (P<0.01), acetate (P<0.01) and butyrate concentrations (P<0.01) were higher by the end of the diet enriched with arabinoxylan and resistant starch compared with those resulting from the Western-style diet. The concentrations of isobutyrate (P = 0.05) and isovalerate (P = 0.03) decreased in response to the arabinoxylan and resistant starch enriched diet, indicating reduced protein fermentation. In conclusion, arabinoxylan and resistant starch intake changes the microbiome and short-chain fatty acid compositions, with potential beneficial effects on colonic health and metabolic syndrome. ClinicalTrials.gov NCT01618526.

A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices.

PubMed

van der Palen, Job; Thomas, Mike; Chrystyn, Henry; Sharma, Raj K; van der Valk, Paul Dlpm; Goosens, Martijn; Wilkinson, Tom; Stonham, Carol; Chauhan, Anoop J; Imber, Varsha; Zhu, Chang-Qing; Svedsater, Henrik; Barnes, Neil C

2016-11-24

Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57-70%) made no errors using ELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other devices (all P⩽0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers.

The effect of a standardised source of divided attention in airway management: A randomised, crossover, interventional manikin study.

PubMed

Prottengeier, Johannes; Petzoldt, Marlen; Jess, Nikola; Moritz, Andreas; Gall, Christine; Schmidt, Joachim; Breuer, Georg

2016-03-01

Dual-tasking, the need to divide attention between concurrent tasks, causes a severe increase in workload in emergency situations and yet there is no standardised training simulation scenario for this key difficulty. We introduced and validated a quantifiable source of divided attention and investigated its effects on performance and workload in airway management. A randomised, crossover, interventional simulation study. Center for Training and Simulation, Department of Anaesthesiology, Erlangen University Hospital, Germany. One hundred and fifty volunteer medical students, paramedics and anaesthesiologists of all levels of training. Participants secured the airway of a manikin using a supraglottic airway, conventional endotracheal intubation and video-assisted endotracheal intubation with and without the Paced Auditory Serial Addition Test (PASAT), which served as a quantifiable source of divided attention. Primary endpoint was the time for the completion of each airway task. Secondary endpoints were the number of procedural mistakes made and the perceived workload as measured by the National Aeronautics and Space Administration's task load index (NASA-TLX). This is a six-dimensional questionnaire, which assesses the perception of demands, performance and frustration with respect to a task on a scale of 0 to 100. All 150 participants completed the tests. Volunteers perceived our test to be challenging (99%) and the experience of stress and distraction true to an emergency situation (80%), but still fair (98%) and entertaining (95%). The negative effects of divided attention were reproducible in participants of all levels of expertise. Time consumption and perceived workload increased and almost half the participants make procedural mistakes under divided attention. The supraglottic airway technique was least affected by divided attention. The scenario was effective for simulation training involving divided attention in acute care medicine. The significant effects on performance and perceived workload demonstrate the validity of the model, which was also characterised by high acceptability, technical simplicity and a novel degree of standardisation.

Bi-level CPAP does not improve gas exchange when compared with conventional CPAP for the treatment of neonates recovering from respiratory distress syndrome.

PubMed

Lampland, Andrea L; Plumm, Brenda; Worwa, Cathy; Meyers, Patricia; Mammel, Mark C

2015-01-01

We hypothesised that short-term application of bi-level nasal continuous positive airway pressure CPAP (SiPAP) compared with conventional nasal CPAP (nCPAP) at the same mean airway pressure in infants with persistent oxygen need recovering from respiratory distress syndrome would improve CO2 removal with no change in oxygen requirement. Non-blinded, randomised, observational four-period crossover study. Level III NICU; low-birthweight infants requiring CPAP and oxygen while recovering from respiratory distress syndrome. Infants requiring nasal CPAP for >24 h prior to study enrolment, and fraction of inspired oxygen requirement (FiO2) of 0.25-0.5, were randomised to either nCPAP or SiPAP. A crossover design with four 1 h treatment periods was used such that each infant received both treatments twice. Oxygen saturations (SaO2), transcutaneous CO2 (tcCO2) and vital signs were monitored continuously. Polysomnographic recordings were analysed for apnoea, bradycardia and oxygen desaturation. Twenty low-birthweight infants receiving 0.3±0.04% supplemental oxygen on CPAP of 6 cm H2O were studied at an average of 33 days of age (±23 days, SD). There were no differences in tcCO2 or other physiological parameters except mean blood pressure, which was lower during nCPAP (52.3±8.3 vs 54.4±9.1 mm Hg; ±SD; p<0.01). No differences in short or prolonged apnoea, bradycardia or significant desaturation events were observed. At similar mean airway pressures, SiPAP does not improve CO2 removal, oxygenation or other studied physiological parameters with the exception of mean blood pressure, which was not clinically significant. NCT01053455. 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.

Short-term effects of three slow expiratory airway clearance techniques in patients with bronchiectasis: a randomised crossover trial.

PubMed

Herrero-Cortina, B; Vilaró, J; Martí, D; Torres, A; San Miguel-Pagola, M; Alcaraz, V; Polverino, E

2016-12-01

To compare the efficacy of three slow expiratory airway clearance techniques (ACTs). Randomised crossover trial. Tertiary hospital. Thirty-one outpatients with bronchiectasis and chronic sputum expectoration. Autogenic drainage (AD), slow expiration with glottis opened in lateral posture (ELTGOL), and temporary positive expiratory pressure (TPEP). Sputum expectoration during each session (primary endpoint) and in the 24-hour period after each session. Leicester Cough Questionnaire (LCQ) score and spirometry results were recorded at the beginning and after each week of treatment. Data were summarised as median difference [95% confidence interval (CI)]. Median (interquartile range) daily expectoration at baseline was 21.1 (15.3 to 35.6)g. During physiotherapy sessions, AD and ELTGOL expectorated more sputum than TPEP [AD vs TPEP 3.1g (95% CI 1.5 to 4.8); ELTGOL vs TPEP 3.6g (95% CI 2.8 to 7.1)], while overall expectoration in the 24-hour period after each session was similar for all techniques (P=0.8). Sputum clearance at 24hours post-intervention was lower than baseline assessment for all techniques [AD vs baseline -10.0g (95% CI -15.0 to -6.8); ELTGOL vs baseline -9.2g (95% CI -14.2 to -7.9); TPEP vs baseline -6.0g (95% CI -12.0 to -6.1)]. The LCQ score increased with all techniques (AD 0.5, 95% CI 0.1 to 0.5; ELTGOL 0.9, 95% CI 0.5 to 2.1; TPEP 0.4, 95% CI 0.1 to 1.2), being similar for all ACTs (P=0.6). No changes in lung function were observed. Slow expiratory ACTs enhance mucus clearance during treatment sessions, and reduce expectoration for the rest of the day in patients with bronchiectasis. NCT01854788. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices

PubMed Central

van der Palen, Job; Thomas, Mike; Chrystyn, Henry; Sharma, Raj K; van der Valk, Paul DLPM; Goosens, Martijn; Wilkinson, Tom; Stonham, Carol; Chauhan, Anoop J; Imber, Varsha; Zhu, Chang-Qing; Svedsater, Henrik; Barnes, Neil C

2016-01-01

Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57–70%) made no errors using ELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other devices (all P⩽0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers. PMID:27883002

Advantages and disadvantages of graduated and inverse graduated compression hosiery in patients with chronic venous insufficiency and healthy volunteers: A prospective, mono-centric, blinded, open randomised, controlled and cross-over trial.

PubMed

Riebe, Helene; Konschake, Wolfgang; Haase, Hermann; Jünger, Michael

2018-02-01

Background The therapeutic effectiveness of compression therapy depends on the selection of compression hosiery. Objectives To assess efficacy and tolerability of graduated elastic compression stockings (GECS) and inverse graduated elastic compression stockings (PECS). Methods Thirty-two healthy volunteers and thirty-two patients with chronic venous insufficiency were analysed; wear period: one week for each stocking type (randomised, blinded). volume reduction of 'Lower leg' (Image3D®) and 'Distal leg and foot' (water plethysmography). clinical symptoms of chronic venous insufficiency assessed by the Venous Clinical Severity Score, side effects and wear comfort in both groups. Results Volume of 'Lower leg': significant reduction in healthy volunteers (mean GECS: -37.5 mL, mean PECS: -37.2 mL) and in patients (mean GECS: -55.6 mL, mean PECS: -41.6 mL). Volume of 'Distal lower leg and foot': significant reduction in healthy volunteers (mean GECS: -27 mL, mean PECS: -16.7 mL), significant reduction in patients by GECS (mean: -43.4 mL), but non-significant reduction by PECS (mean: -22.6 mL). Clinical symptoms of chronic venous insufficiency were improved significantly better with GECS than with PECS, p < 0.001. GECS led to more painful constrictions, p = 0.047, PECS slipped down more often, p < 0.001. Conclusion GECS and PECS reduce volume of the segment 'Lower leg' in patients and healthy volunteers. Patients' volume of the 'Distal lower leg and foot', however, were diminished significantly only by GECS ( p = 0.0001). Patients' complaints were improved by both GECS and PECS, and GECS were superior to PECS.

The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial.

PubMed

Black, R Neil A; Ennis, Cieran N; Young, Ian S; Hunter, Steven J; Atkinson, A Brew; Bell, Patrick M

2014-01-01

Assess insulin sensitivity after treatment with a selective PPAR-alpha agonist compared to an HMG CoA reductase inhibitor in human subjects with type 2 diabetes mellitus. Thirteen subjects with Type 2 diabetes mellitus were studied in a double-blind crossover design with 4-week placebo run-in and washout and 12-week treatment periods, randomised to micronised fenofibrate 267 mg or atorvastatin 10mg daily followed by the alternate drug in the second period. Insulin resistance was measured using the isoglycaemic hyperinsulinaemic clamp method with isotope dilution. Weight, physical activity and other medications did not change. Total cholesterol (mean +/- standard error) was 4.60+/-0.21 versus 3.9+/-0.22 mmol/L after fenofibrate and atorvastatin respectively, p<0.05. LDL was 2.70+/-0.19 versus 1.95+/-0.23 mmol/L, p<0.05 and triglyceride 1.64+/-0.23 versus 1.84+/-0.26 mmol/L, p<0.05. Insulin-stimulated whole-body glucose disposal (35.4+/-3.1 versus 33.2+/-3.0 μmol/kg/min) and nadir endogenous glucose production (6.2+/-1.4 versus 7.0+/-1.1 μmol/kg/min) revealed no significant differences in effects of the treatments. In human subjects with Type 2 diabetes mellitus there were characteristic differences in lipid profile changes but no difference in insulin sensitivity after treatment with micronised fenofibrate compared to atorvastatin. This study finds no evidence of increased insulin sensitivity using this selective PPAR-alpha agonist over a commonly used statin at these doses. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial.

PubMed

De Boeck, K; Haarman, E; Hull, J; Lands, L C; Moeller, A; Munck, A; Riethmüller, J; Tiddens, H; Volpi, S; Leadbetter, J; Charlton, B; Malfroot, A

2017-05-01

Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF). The efficacy of inhaled mannitol in children with CF aged 6-17years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400mg every 12h or matching placebo for 8weeks, followed by an 8week washout and an 8week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1). A total of 92 subjects were studied, with a mean age of 12years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p=0.004) higher compared to placebo or a 4.97% (p=0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p=0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p=0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group. In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531). Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Children's self-regulation of eating provides no defense against television and online food marketing.

PubMed

Norman, Jennifer; Kelly, Bridget; McMahon, Anne-T; Boyland, Emma; Baur, Louise A; Chapman, Kathy; King, Lesley; Hughes, Clare; Bauman, Adrian

2018-06-01

Exposure to unhealthy food marketing stimulates children's food consumption. A child's responsiveness is influenced by individual factors, resulting in an increased vulnerability to advertising effects among some children. Whether these differential responses may be altered by different parental feeding behaviours is unclear. The purpose of this study was to determine the relationship between parental feeding practices and children's food intake responses to food advertising exposure. A randomised, crossover, counterbalanced, within subject trial was conducted across four, six-day holiday camps in New South Wales, Australia between April 2016 and January 2017 with 160 children (7-12 years, n = 40/camp). Children were randomised to either a multiple media (TV and Internet) or single media (TV) condition and exposed to food (3 days) and non-food (3 days) advertising in an online game and/or a cartoon. Children's food consumption (kilojoules (kJ)) was measured at a snack immediately after advertising exposure and then at lunch later in the day. Parents completed the Child Feeding Questionnaire, and 'restriction' and 'pressure to eat' subscale scores were calculated. While food advertising affected all children in the multiple media condition, there was an increased effect on snack intake among children whose parents reported pressuring them to eat, with children consuming an additional 356 kJ after food advertising compared with non-food advertising. This was 209 kJ more than children whose parents did not pressure them to eat. In the single media condition, only children whose parents reported restrictive feeding practices ate more at lunch on food advertising days than non-food advertising days (240 kJ). These data highlight an increased susceptibility to food advertising among children whose parents report controlling feeding practices. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of almonds on inflammation and oxidative stress in Chinese patients with type 2 diabetes mellitus: a randomized crossover controlled feeding trial

USDA-ARS?s Scientific Manuscript database

Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-wk randomized, crossover, controlled feeding trial was that almond consumption would ameliorate inflammation and oxidative stress in Chinese patients with type 2...

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

PubMed Central

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

2018-01-01

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

Is inertial flywheel resistance training superior to gravity-dependent resistance training in improving muscle strength? A systematic review with meta-analyses.

PubMed

Vicens-Bordas, J; Esteve, E; Fort-Vanmeerhaeghe, A; Bandholm, T; Thorborg, K

2018-01-01

The primary aim of this systematic review was to determine if inertial flywheel resistance training is superior to gravity-dependent resistance training in improving muscle strength. The secondary aim was to determine whether inertial flywheel resistance training is superior to gravity-dependent resistance training in improving other muscular adaptations. A systematic review with meta-analyses of randomised and non-randomised controlled trials. We searched MEDLINE, Scopus, SPORTDiscus, Web of Science and Cochrane Central Register of Controlled Trials with no publication date restrictions until November 2016. We performed meta-analyses on randomised and non-randomised controlled trials to determine the standardized mean difference between the effects of inertial flywheel and gravity-dependent resistance training on muscle strength. A total of 76 and 71 participants were included in the primary and secondary analyses, respectively. After systematic review, we included three randomised and four non-randomised controlled trials. In the primary analysis for the primary outcome muscle strength, the pooled results from randomised controlled trials showed no difference (SMD=-0.05; 95%CI -0.51 to 0.40; p=0.82; I 2 =0%). In the secondary analyses of the primary outcome, the pooled results from non-randomised controlled trials showed no difference (SMD=0.02; 95%CI -0.45 to 0.49; p=0.93; I 2 =0%; and SMD=0.03; 95%CI -0.43 to 0.50; p=0.88; I 2 =0%). Meta-analysis on secondary outcomes could not be performed. Based on the available data, inertial flywheel resistance training was not superior to gravity-dependent resistance training in enhancing muscle strength. Data for other strength variables and other muscular adaptations was insufficient to draw firm conclusions from. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Effect of a chitosan additive to a Sn2+-containing toothpaste on its anti-erosive/anti-abrasive efficacy--a controlled randomised in situ trial.

PubMed

Schlueter, N; Klimek, J; Ganss, C

2014-01-01

It is well known that Sn(2+) is a notable anti-erosive agent. There are indications that biopolymers such as chitosan can enhance the effect of Sn(2+), at least in vitro. However, little information exists about their anti-erosive/anti-abrasive in situ effects. In the present in situ study, the efficacy of Sn(2+)-containing toothpastes in the presence or absence of chitosan was tested. Ten subjects participated in the randomised crossover study, wearing mandibular appliances with human enamel specimens. Specimens were extraorally demineralised (7 days, 0.5% citric acid, pH 2.6; 6 × 2 min/day) and intraorally exposed to toothpaste suspensions (2 × 2 min/day). Within the suspension immersion time, one half of the specimens were additionally brushed intraorally with a powered toothbrush (5 s, 2.5 N). Tested preparations were a placebo toothpaste (negative control), two experimental toothpastes (F/Sn = 1,400 ppm F(-), 3,500 ppm Sn(2+); F/Sn/chitosan = 1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5 % chitosan) and an SnF2-containing gel (positive control, GelKam = 3,000 ppm Sn(2+), 1,000 ppm F(-)). Substance loss was quantified profilometrically (μm). In the placebo group, tissue loss was 11.2 ± 4.6 (immersion in suspension) and 17.7 ± 4.7 (immersion in suspension + brushing). Immersion in each Sn(2+)-containing suspension significantly reduced tissue loss (p ≤ 0.01); after immersion in suspension + brushing, only the treatments with GelKam (5.4 ± 5.5) and with F/Sn/chitosan (9.6 ± 5.6) significantly reduced loss [both p ≤ 0.05 compared to placebo; F/Sn 12.8 ± 6.4 (not significant)] Chitosan enhanced the efficacy of the Sn(2+)-containing toothpaste as an anti-erosive/anti-abrasive agent. The use of Sn(2+)- and chitosan-containing toothpaste is a good option for symptomatic therapy in patients with regular acid impacts.

Can coenzyme Q10 supplementation effectively reduce human tumour necrosis factor-α and interleukin-6 levels in chronic diseases? Protocol for a systematic review and meta-analysis of randomised controlled trials.

PubMed

Farsi, Farnaz; Heshmati, Javad; Janani, Leila; Irandoost, Pardis; Mesri Alamdari, Naeimeh; Keshtkar, Abbasali; Akbari, Abolfazl; Vafa, Mohammadreza

2017-10-08

Inflammation, as a critical factor, can cause numerous chronic diseases by creating various proinflammatory cytokines. Coenzyme Q10 (CoQ10) can potentially exert an anti-inflammatory agent; in turn, this agent can reduce the systemic inflammatory response. The aims of this study are to conduct a comprehensive systematic review and a meta-analysis for the determination of the CoQ10 efficacy on the changes in serum interleukin-6 (IL-6) and the tumour necrosis factor-α (TNF-α) levels in unhealthy subjects. We will conduct an electronic search for articles published between January 1990 and January 2017 using a prespecified search strategy in MEDLINE, SCOPUS, EMBASE, CENTRAL and Web of Science.Our search will focus only on randomised controlled clinical trials in unhealthy subjects that employ either a parallel or a crossover design; this search will involve concurrent control groups. The primary outcomes of the literature are to determine the CoQ10 efficacy on the changes in the serum IL-6 and the TNF-α levels in unhealthy subjects. Secondary outcomes such as body mass index, serum adiponectin and high-sensitivity C-reactive protein levels, lipid profile and the heterogeneity assessment of the primary studies will be evaluated. The stages of screen articles, the extracts of relevant data and the assessment of study quality using the Cochrane risk of bias tool will be conducted independently by the two reviewers. Any disagreement will be resolved by discussion with a third person. If the number of eligible studies is sufficient, we will carry out a meta-analysis according to both outcomes. This study is the protocol for a systematic review and no ethics approval is needed. The findings from the full systematic review will be published in a peer-reviewed journal, and they will also be exhibited at national/international academic and clinical conferences. CRD42016052200. © 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.

Physical interventions to interrupt or reduce the spread of respiratory viruses.

PubMed

Jefferson, Tom; Del Mar, Chris; Dooley, Liz; Ferroni, Eliana; Al-Ansary, Lubna A; Bawazeer, Ghada A; van Driel, Mieke L; Nair, Sreekumaran; Foxlee, Ruth; Rivetti, Alessandro

2010-01-20

Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a world-wide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe. To systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2); MEDLINE (1966 to May 2009); OLDMEDLINE (1950 to 1965); EMBASE (1990 to May 2009); and CINAHL (1982 to May 2009). We scanned 2958 titles, excluded 2790 and retrieved the full papers of 168 trials, to include 59 papers of 60 studies. We included any physical interventions (isolation, quarantine, social distancing, barriers, personal protection and hygiene) to prevent transmission of respiratory viruses. We included the following study designs: randomised controlled trials (RCTs), cohorts, case controls, cross-over, before-after, and time series studies. We used a standardised form to assess trial eligibility. RCTs were assessed by: randomisation method; allocation generation; concealment; blinding; and follow up. Non-RCTs were assessed for the presence of potential confounders, and classified into low, medium, and high risks of bias. The risk of bias for the four RCTs, and most cluster RCTs, was high. The observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis.The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. Six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that N95 respirators were superior to simple surgical masks, but were more expensive, uncomfortable, and caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. There was limited evidence that social distancing was effective especially if related to the risk of exposure. Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

PubMed Central

Hussain, I; Brady, C; Swinn, M; Mathias, C; Fowler, C

2001-01-01

OBJECTIVES—To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy.
METHODS—Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital.
RESULTS—Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication.
CONCLUSIONS—Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.

 PMID:11511713

Anticonvulsants for preventing seizures in patients with chronic subdural haematoma.

PubMed

Ratilal, Bernardo O; Pappamikail, Lia; Costa, João; Sampaio, Cristina

2013-06-06

Anticonvulsant therapy is sometimes used prophylactically in patients with chronic subdural haematoma, although the benefit is unclear. To assess the effects of prophylactic anticonvulsants in patients with chronic subdural haematoma, in both the pre- and post-operative periods. We searched the Cochrane Injuries Group's Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), PubMed, LILACS, and the databases clinicaltrials.gov, the WHO International Clinical Trials Registry Platform, and Current Controlled Trials. The search was through 27th March 2013. Randomised controlled trials comparing any anticonvulsant versus placebo or no intervention. Three authors screened the search results to identify relevant studies. No studies met the inclusion criteria for the review. No randomised controlled trials were identified. No formal recommendations can be made about the use of prophylactic anticonvulsants in patients with chronic subdural haematoma based on the literature currently available. There are no randomised controlled trials on this topic, and non-controlled studies have conflicting results. There is an urgent need for well-designed randomised controlled trials.

Double-Blind, Placebo-Controlled, Crossover Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in College Students with ADHD

ERIC Educational Resources Information Center

DuPaul, George J.; Weyandt, Lisa L.; Rossi, Joseph S.; Vilardo, Brigid A.; O'Dell, Sean M.; Carson, Kristen M.; Verdi, Genevieve; Swentosky, Anthony

2012-01-01

Objective: To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design. Method: Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five…

Atomoxetine for Hyperactivity in Autism Spectrum Disorders: Placebo-Controlled Crossover Pilot Trial

ERIC Educational Resources Information Center

Arnold, L. Eugene; Aman, Michael G.; Cook, Amelia M.; Witwer, Andrea N.; Hall, Kristy L.; Thompson, Susan; Ramadan, Yaser

2006-01-01

Objective: To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD). Method: Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6…

Targeted full energy and protein delivery in critically ill patients: a study protocol for a pilot randomised control trial (FEED Trial).

PubMed

Fetterplace, Kate; Deane, Adam M; Tierney, Audrey; Beach, Lisa; Knight, Laura D; Rechnitzer, Thomas; Forsyth, Adrienne; Mourtzakis, Marina; Presneill, Jeffrey; MacIsaac, Christopher

2018-01-01

Current guidelines for the provision of protein for critically ill patients are based on incomplete evidence, due to limited data from randomised controlled trials. The present pilot randomised controlled trial is part of a program of work to expand knowledge about the clinical effects of protein delivery to critically ill patients. The primary aim of this pilot study is to determine whether an enteral feeding protocol using a volume target, with additional protein supplementation, delivers a greater amount of protein and energy to mechanically ventilated critically ill patients than a standard nutrition protocol. The secondary aims are to evaluate the potential effects of this feeding strategy on muscle mass and other patient-centred outcomes. This prospective, single-centred, pilot, randomised control trial will include 60 participants who are mechanically ventilated and can be enterally fed. Following informed consent, the participants receiving enteral nutrition in the intensive care unit (ICU) will be allocated using a randomisation algorithm in a 1:1 ratio to the intervention (high-protein daily volume-based feeding protocol, providing 25 kcal/kg and 1.5 g/kg protein) or standard care (hourly rate-based feeding protocol providing 25 kcal/kg and 1 g/kg protein). The co-primary outcomes are the average daily protein and energy delivered to the end of day 15 following randomisation. The secondary outcomes include change in quadriceps muscle layer thickness (QMLT) from baseline (prior to randomisation) to ICU discharge and other nutritional and patient-centred outcomes. This trial aims to examine whether a volume-based feeding protocol with supplemental protein increases protein and energy delivery. The potential effect of such increases on muscle mass loss will be explored. These outcomes will assist in formulating larger randomised control trials to assess mortality and morbidity. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: 12615000876594 UTN: U1111-1172-8563.

The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive-behavioural therapy.

PubMed

Langdon, Peter E; Murphy, Glynis H; Shepstone, Lee; Wilson, Edward C F; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

2016-03-01

There is a growing interest in using cognitive-behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. None. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.

Electronic bidirectional valve circuit prevents crossover distortion and threshold effect

NASA Technical Reports Server (NTRS)

Kernick, A.

1966-01-01

Four-terminal network forms a bidirectional valve which will switch or alternate an ac signal without crossover distortion or threshold effect. In this network, an isolated control signal is sufficient for circuit turn-on.

Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.

PubMed

Schulz, Constanze; Timm, Jürgen; Cordes, Joachim; Gründer, Gerhard; Mühlbauer, Bernd; Rüther, Eckart; Heinze, Martin

2016-06-01

The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types. The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia. In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed. The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful. © The Author(s) 2016.

Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.

PubMed

Tey, S L; Salleh, N B; Henry, C J; Forde, C G

2017-09-01

Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.

Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure.

PubMed

Gavin, A D; Struthers, A D

2005-06-01

To study whether the effect of allopurinol on improvement of endothelial dysfunction in chronic heart failure (CHF) translates into improved exercise capacity and to examine whether allopurinol also improves B-type natriuretic peptide (BNP), the other important prognostic marker of CHF. Randomised, double blind, placebo controlled crossover trial. Teaching hospital. 50 patients with CHF (New York Heart Association functional classes II and III) were recruited. 50 patients with CHF were randomly assigned to three months' treatment with allopurinol (300 mg/day) or placebo. At two and three months into treatment, they underwent a modified Bruce exercise protocol and a six minute walk test. Blood was taken for BNP and haemoglobin analysis. Neither exercise test was altered by allopurinol. However, plasma BNP concentrations fell significantly (p = 0.035) with allopurinol (11.9 pmol/l) versus placebo (14.4 pmol/l). Haemoglobin concentrations also fell highly significantly with allopurinol (p = 0.001). An important negative finding is that despite high hopes for it, allopurinol had no effect on exercise capacity in CHF. On the other hand, allopurinol did reduce BNP, which is the best available surrogate marker for prognosis in CHF.

The effects of L-theanine, caffeine and their combination on cognition and mood.

PubMed

Haskell, Crystal F; Kennedy, David O; Milne, Anthea L; Wesnes, Keith A; Scholey, Andrew B

2008-02-01

L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.

Low subjective socioeconomic status stimulates orexigenic hormone ghrelin - A randomised trial.

PubMed

Sim, A Y; Lim, E X; Leow, M K; Cheon, B K

2018-03-01

Recent evidence suggests that lower perceived socioeconomic status is linked to increased appetite and intake of greater calories. Yet, whether insecurity of socioeconomic resources directly influences regulatory systems of appetite and energy intake is not known. Considering psychological states, mindsets and beliefs have shown to meaningfully affect physiological responses to food, the present study tested the hypothesis that low subjective socioeconomic status (SSS) will have a direct influence on physiological responses, such as appetite-related hormones (ghrelin, pancreatic polypeptide and insulin). Forty-eight healthy males were randomly (crossover, counterbalanced) assigned, to two experimental conditions where participants were either experimentally induced to feel low SSS or not (control; CON). Feelings of low SSS resulted in an increase in active ghrelin (an orexigenic hormone) following the SSS manipulation compared with baseline, while no change in active ghrelin was observed in CON. Furthermore, participants reported lower fullness and satiety following low SSS compared with CON. Our findings demonstrate that SSS may influence hunger regulation and appetite, and suggest that physiological systems regulating energy balance (i.e. caloric resources) may also be sensitive to perceived deprivation or imbalances in critical non-food resources (socioeconomic resources). Copyright © 2018 Elsevier Ltd. All rights reserved.

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero, One and Five in India: A Decomposition Analysis.

PubMed

Dubey, Manisha; Ram, Usha; Ram, Faujdar

2015-01-01

Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover. We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981-2009 for 16 Indian states by sex (comprising of India's 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover. India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women). For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1-59 months in high child mortality areas can help India to attain this crossover early.

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Treatment Failure With Rhythm and Rate Control Strategies in Patients With Atrial Fibrillation and Congestive Heart Failure: An AF-CHF Substudy.

PubMed

Dyrda, Katia; Roy, Denis; Leduc, Hugues; Talajic, Mario; Stevenson, Lynne Warner; Guerra, Peter G; Andrade, Jason; Dubuc, Marc; Macle, Laurent; Thibault, Bernard; Rivard, Lena; Khairy, Paul

2015-12-01

Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival. A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37  ±  19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter-defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73-1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73-2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79-1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873). Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival. © 2015 Wiley Periodicals, Inc.

Simvastatin in the treatment of asthma: lack of steroid-sparing effect.

PubMed

Cowan, Douglas C; Cowan, Jan O; Palmay, Rochelle; Williamson, Avis; Taylor, D Robin

2010-10-01

Statins have anti-inflammatory actions which in theory are potentially beneficial in asthma. Small trials have failed to show a significant benefit, but a systematic study to evaluate the steroid-sparing effect of statin treatment has not been carried out. A randomised, placebo-controlled, crossover trial was conducted of simvastatin 40 mg at night with simultaneous stepwise reduction of fluticasone propionate dose until loss of control occurred, followed by an increase until regain of control ('minimum' dose required) in 51 patients with asthma and sputum eosinophils (steroid-free) ≥ 2%. 43 patients completed the study. There was no significant difference in 'minimum' inhaled corticosteroid (ICS) dose requirement between simvastatin and placebo: (median (IQR) 50 μg daily (0-250) vs 100 μg daily (0-250), p=0.931). 'Minimum' dose distribution was similar (p=0.269). The fluticasone dose at which loss of control occurred did not differ significantly between simvastatin and placebo (p=0.404). In patients with loss of control in both treatment arms, fluticasone dose at loss of control was similar with simvastatin and placebo (median (IQR) 50 μg daily (0-100) for both, p=0.620). In those patients who reached 0 μg/day (n=18), Astma Control Questionnaire (ACQ) was lower (p=0.037), forced expiratory volume in 1 s (FEV(1)) higher (p<0.01) and sputum eosinophils lower with simvastatin compared with placebo (9.5% compared with 25.4%, p=0.033). Simvastatin does not have clinically important steroid-sparing effects in patients with eosinophilic asthma. In the absence of steroid, simvastatin is associated with minor improvements in symptoms and lung function, and a reduction in sputum eosinophils. Clinical trial number ACTRN12606000531516.

Quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice - systematic review.

PubMed

Heinmüller, Stefan; Schneider, Antonius; Linde, Klaus

2016-04-23

Academic infrastructures and networks for clinical research in primary care receive little funding in Germany. We aimed to provide an overview of the quantity, topics, methods and findings of randomised controlled trials published by German university departments of general practice. We searched Scopus (last search done in April 2015), publication lists of institutes and references of included articles. We included randomised trials published between January 2000 and December 2014 with a first or last author affiliated with a German university department of general practice or family medicine. Risk of bias was assessed with the Cochrane tool, and study findings were quantified using standardised mean differences (SMDs). Thirty-three trials met the inclusion criteria. Seventeen were cluster-randomised trials, with a majority investigating interventions aimed at improving processes compared with usual care. Sample sizes varied between 6 and 606 clusters and 168 and 7807 participants. The most frequent methodological problem was risk of selection bias due to recruitment of individuals after randomisation of clusters. Effects of interventions over usual care were mostly small (SMD <0.3). Sixteen trials randomising individual participants addressed a variety of treatment and educational interventions. Sample sizes varied between 20 and 1620 participants. The methodological quality of the trials was highly variable. Again, effects of experimental interventions over controls were mostly small. Despite limited funding, German university institutes of general practice or family medicine are increasingly performing randomised trials. Cluster-randomised trials on practice improvement are a focus, but problems with allocation concealment are frequent.

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks.

PubMed

Smit, H J; Keenan, E; Kovacs, E M R; Wiseman, S A; Mela, D J; Rogers, P J

2012-09-01

Fabuless (Olibra) is a commercially structured lipid emulsion, claimed to be a food ingredient that is effective for food intake and appetite reduction. The present study assessed its efficacy in a yoghurt-based mini-drink undergoing low or minimal food manufacturing (thermal and shear) processes. Study 1: Twenty-four healthy volunteers (16 female, 8 male; age: 18-47 years; body mass index (BMI): 17-28 kg m(-2)) took part in a randomised, placebo-controlled, double-blind parallel crossover trial. Consumption of a minimally processed 'preload' mini-drink (containing two different doses of Fabuless or a control fat) at 2 h after breakfast was followed by appetite and mood ratings, and food intake measured in ad libitum meals at 3 and 7 h post consumption of the preload. Study 2: As Study 1 (16 female, 8 male; age: 20-54 years; BMI: 21-30 kg m(-2)). A chilled, virtually unprocessed, preload breakfast mini-drink (containing minimally processed Fabuless or a control fat) was provided 5 min after a standardised breakfast, followed by appetite and mood ratings, and food intake measured in ad libitum meals at 4 and 8 h post consumption of the preload. The structured lipid emulsion tested had no significant effect on the primary measures of food intake or appetite. Even when exposed to minimal food-manufacturing conditions, Fabuless showed no efficacy on measures of appetite and food intake.

Rationale, design and methods for a randomised and controlled trial of the impact of virtual reality games on motor competence, physical activity, and mental health in children with developmental coordination disorder.

PubMed

Straker, Leon M; Campbell, Amity C; Jensen, Lyn M; Metcalf, Deborah R; Smith, Anne J; Abbott, Rebecca A; Pollock, Clare M; Piek, Jan P

2011-08-18

A healthy start to life requires adequate motor development and physical activity participation. Currently 5-15% of children have impaired motor development without any obvious disorder. These children are at greater risk of obesity, musculoskeletal disorders, low social confidence and poor mental health. Traditional electronic game use may impact on motor development and physical activity creating a vicious cycle. However new virtual reality (VR) game interfaces may provide motor experiences that enhance motor development and lead to an increase in motor coordination and better physical activity and mental health outcomes. VR games are beginning to be used for rehabilitation, however there is no reported trial of the impact of these games on motor coordination in children with developmental coordination disorder. This cross-over randomised and controlled trial will examine whether motor coordination is enhanced by access to active electronic games and whether daily activity, attitudes to physical activity and mental health are also enhanced. Thirty children aged 10-12 years with poor motor coordination (≤ 15th percentile) will be recruited and randomised to a balanced ordering of 'no active electronic games' and 'active electronic games'. Each child will participate in both conditions for 16 weeks, and be assessed prior to participation and at the end of each condition. The primary outcome is motor coordination, assessed by kinematic and kinetic motion analysis laboratory measures. Physical activity and sedentary behaviour will be assessed by accelerometry, coordination in daily life by parent report questionnaire and attitudes to physical activity, self-confidence, anxiety and depressed mood will be assessed by self report questionnaire. A sample of 30 will provide a power of > 0.9 for detecting a 5 point difference in motor coordination on the MABC-2 TIS scale (mean 17, sd = 5). This is the first trial to examine the impact of new virtual reality games on motor coordination in children with developmental coordination disorder. The findings will provide critical information to understand whether these electronic games can be used to have a positive impact on the physical and mental health of these children. Given the importance of adequate motor coordination, physical activity and mental health in childhood, this project can inform interventions which could have a profound impact on the long term health of this group of children. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000400965.

Rationale, design and methods for a randomised and controlled trial of the impact of virtual reality games on motor competence, physical activity, and mental health in children with developmental coordination disorder

PubMed Central

2011-01-01

Background A healthy start to life requires adequate motor development and physical activity participation. Currently 5-15% of children have impaired motor development without any obvious disorder. These children are at greater risk of obesity, musculoskeletal disorders, low social confidence and poor mental health. Traditional electronic game use may impact on motor development and physical activity creating a vicious cycle. However new virtual reality (VR) game interfaces may provide motor experiences that enhance motor development and lead to an increase in motor coordination and better physical activity and mental health outcomes. VR games are beginning to be used for rehabilitation, however there is no reported trial of the impact of these games on motor coordination in children with developmental coordination disorder. Methods This cross-over randomised and controlled trial will examine whether motor coordination is enhanced by access to active electronic games and whether daily activity, attitudes to physical activity and mental health are also enhanced. Thirty children aged 10-12 years with poor motor coordination (≤ 15th percentile) will be recruited and randomised to a balanced ordering of 'no active electronic games' and 'active electronic games'. Each child will participate in both conditions for 16 weeks, and be assessed prior to participation and at the end of each condition. The primary outcome is motor coordination, assessed by kinematic and kinetic motion analysis laboratory measures. Physical activity and sedentary behaviour will be assessed by accelerometry, coordination in daily life by parent report questionnaire and attitudes to physical activity, self-confidence, anxiety and depressed mood will be assessed by self report questionnaire. A sample of 30 will provide a power of > 0.9 for detecting a 5 point difference in motor coordination on the MABC-2 TIS scale (mean 17, sd = 5). Discussion This is the first trial to examine the impact of new virtual reality games on motor coordination in children with developmental coordination disorder. The findings will provide critical information to understand whether these electronic games can be used to have a positive impact on the physical and mental health of these children. Given the importance of adequate motor coordination, physical activity and mental health in childhood, this project can inform interventions which could have a profound impact on the long term health of this group of children. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000400965 PMID:21851587

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

PubMed

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

2017-04-26

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

Advantages of using voiced questionnaire and image capture application for data collection from a minority group in rural areas along the Thailand-Myanmar border.

PubMed

Monyarit, Siriporn; Pan-ngum, Wirichada; Lawpoolsri, Saranath; Yimsamran, Surapon; Pongnumkul, Suporn; Kaewkungwal, Jaranit; Singhasivanon, Pratap

2014-01-01

To compare the quality of data collection via electronic data capture (EDC) with voiced questionnaire (QNN) and data image capture features using a tablet versus standard paper-based QNN, to assess the user's perception of using the EDC tool, and to compare user satisfaction with the two methods. Randomised cross-over study. Study sites: This study was conducted in two villages along the Thailand-Myanmar border. This study included 30 community health volunteers (CHVs) and 120 Karen hill tribe villagers. Employing a cross-over study design, the CHVs were allocated randomly to two groups, in which they performed interviews in different sequences using EDC and QNN. Data discrepancies were found between the two data-collection methods, when data from the paper-based and image-capture methods were compared, and when conducting skip pattern questions. More than 90% of the CHVs perceived the EDC to be useful and easy to use. Both interviewers and interviewees were more satisfied with the EDC compared with QNN in terms of format, ease of use, and system speed. The EDC can effectively be used as an alternative method to paper-based QNNs for data collection. It produces more accurate data that can be considered evidence-based.

Spinal cord stimulation for cancer-related pain in adults.

PubMed

Peng, Lihua; Min, Su; Zejun, Zhou; Wei, Ke; Bennett, Michael I

2015-06-29

This is an update of a review first published in The Cochrane Library in Issue 3, 2013. Cancer-related pain places a heavy burden on public health with related high expenditure. Severe pain is associated with a decreased quality of life in patients with cancer. A significant proportion of patients with cancer-related pain are under-treated. There is a need for more effective control of cancer-related pain. Spinal cord stimulation (SCS) may have a role in pain management. The effectiveness and safety of SCS for patients with cancer-related pain is currently unknown. This systematic review evaluated the effectiveness of SCS for cancer-related pain compared with standard care using conventional analgesic medication. We also appraised risk and potential adverse events associated with the use of SCS. This is an update of a review first published in The Cochrane Library in Issue 3, 2013. The search strategy for the update was the same as in the original review. We searched the following bibliographic databases in order to identify relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and CBM (Chinese Biomedical Database) in October 2014. We also handsearched relevant journals. There were no language restrictions. We planned to include randomised controlled trials (RCTs) that directly compared SCS with other interventions with regards to the effectiveness of pain management. We also planned to include cross-over trials that compared SCS with another treatment. We planned to identify non-randomised controlled trials but these would only be included if no RCTs could be found. The literature search for the update of this review found 121 potentially eligible articles. The initial search strategy yielded 430 articles. By scrutinising titles and abstracts, we found 412 articles irrelevant to the analytical purpose of this systematic review due to different scopes of diseases or different methods of intervention (intrathecal infusion system; oral medication) or aims other than pain control (spinal cord function monitoring, bladder function restoration or amelioration of organ metabolism). The remaining 18 trials were reviewed as full manuscripts. No RCTs were identified. Fourteen sporadic case reports and review articles were excluded and four before-and-after case series studies (92 participants) were included. Two review authors independently selected the studies to be included in the review according to the prespecified eligibility criteria. A checklist for methodological quality of non-randomised controlled trials was used (STROBE checklist) and all review authors discussed and agreed on the inclusion of trials and the results of the quality assessment. No new studies were identified for inclusion in this update of the review. Four before-and-after case series studies (a total of 92 participants) met our criteria for inclusion in the previous version of the review. All included trials adopted a visual analogue scale (VAS) to evaluate pain relief. Heterogeneity existed in terms of baseline characteristics, electrode and stimulator parameters, level of implantation and route of implantation; each trial reported data differently. In two trials, pain relief was achieved in 76% (48/63) of participants at the end of the follow-up period. In the third trial, pre-procedure VAS was 6 to 9 (mean 7.43 ); the one-month post-implant VAS was 2 to 4 (mean 3.07); the 12-month post-implant VAS was 1 to 3 (mean 2.67). In the fourth trial, the pre-procedure VAS was 6 to 9 (mean 7.07); 1 to 4 (mean 2.67) at one-month; 1 to 4 (mean 1.87) at 12 months. Analgesic use was largely reduced. The main adverse events were infection of sites of implantation, cerebrospinal fluid (CSF) leakage, pain at the sites of electrodes, dislodgement of the electrodes, and system failure; however, the incidence in participants with cancer could not be calculated. Since all trials were small, non-randomised controlled trials, they carried high or unclear risk of all types of bias. Since the first publication of this review, no new studies were identified. Current evidence is insufficient to establish the role of SCS in treating refractory cancer-related pain. Future randomised studies should focus on the implantation of SCS in participants with cancer-related pain.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial.

PubMed

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst; Brodersen, John

2012-01-01

To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales 'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and 'introvert', with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants-both the participants in the screen group and the control group. This negative impact was greatest for the control group.

Comparison of anticipated and actual control group outcomes in randomised trials in paediatric oncology provides evidence that historically controlled studies are biased in favour of the novel treatment.

PubMed

Moroz, Veronica; Wilson, Jayne S; Kearns, Pamela; Wheatley, Keith

2014-12-10

Historically controlled studies are commonly undertaken in paediatric oncology, despite their potential biases. Our aim was to compare the outcome of the control group in randomised controlled trials (RCTs) in paediatric oncology with those anticipated in the sample size calculations in the protocols. Our rationale was that, had these RCTs been performed as historical control studies instead, the available outcome data used to calculate the sample size in the RCT would have been used as the historical control outcome data. A systematic search was undertaken for published paediatric oncology RCTs using the Cochrane Central Register of Controlled Trials (CENTRAL) database from its inception up to July 2013. Data on sample size assumptions and observed outcomes (timetoevent and proportions) were extracted to calculate differences between randomised and historical control outcomes, and a one-sample t-test was employed to assess whether the difference between anticipated and observed control groups differed from zero. Forty-eight randomised questions were included. The median year of publication was 2005, and the range was from 1976 to 2010. There were 31 superiority and 11 equivalence/noninferiority randomised questions with time-to-event outcomes. The median absolute difference between observed and anticipated control outcomes was 5.0% (range: -23 to +34), and the mean difference was 3.8% (95% CI: +0.57 to +7.0; P = 0.022). Because the observed control group (that is, standard treatment arm) in RCTs performed better than anticipated, we found that historically controlled studies that used similar assumptions for the standard treatment were likely to overestimate the benefit of new treatments, potentially leading to children with cancer being given ineffective therapy that may have additional toxicity.

Occlusal splints for treating sleep bruxism (tooth grinding).

PubMed

Macedo, C R; Silva, A B; Machado, M A; Saconato, H; Prado, G F

2007-10-17

Sleep bruxism is an oral activity characterised by teeth grinding or clenching during sleep. Several treatments for sleep bruxism have been proposed such as pharmacological, psychological, and dental. To evaluate the effectiveness of occlusal splints for the treatment of sleep bruxism with alternative interventions, placebo or no treatment. We searched the Cochrane Oral Health Group's Trials Register (to May 2007); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1); MEDLINE (1966 to May 2007); EMBASE (1980 to May 2007); LILACS (1982 to May 2007); Biblioteca Brasileira de Odontologia (1982 to May 2007); Dissertation, Theses and Abstracts (1981 to May 2007); and handsearched abstracts of particular importance to this review. Additional reports were identified from the reference lists of retrieved reports and from article reviews about treating sleep bruxism. There were no language restrictions. We selected randomised or quasi-randomised controlled trials (RCTs), in which splint therapy was compared concurrently to no treatment, other occlusal appliances, or any other intervention in participants with sleep bruxism. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third review author consulted. The author of the primary study was contacted when necessary. Thirty-two potentially relevant RCTs were identified. Twenty-four trials were excluded. Five RCTs were included. Occlusal splint was compared to: palatal splint, mandibular advancement device, transcutaneous electric nerve stimulation, and no treatment. There was just one common outcome (arousal index) which was combined in a meta-analysis. No statistically significant differences between the occlusal splint and control groups were found in the meta-analyses. There is not sufficient evidence to state that the occlusal splint is effective for treating sleep bruxism. Indication of its use is questionable with regard to sleep outcomes, but it may be that there is some benefit with regard to tooth wear. This systematic review suggests the need for further investigation in more controlled RCTs that pay attention to method of allocation, outcome assessment, large sample size, and sufficient duration of follow up. The study design must be parallel, in order to eliminate the bias provided by studies of cross-over type. A standardisation of the outcomes of the treatment of sleep bruxism should be established in the RCTs.

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

PubMed

Moreno-López, Laura; Manktelow, Anne E; Sahakian, Barbara J; Menon, David K; Stamatakis, Emmanuel A

2017-02-01

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

A Link between Meiotic Prophase Progression and CrossoverControl

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

Carlton, Peter M.; Farruggio, Alfonso P.; Dernburg, Abby F.

2005-07-06

During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealedmore » that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.« less

A Quality Control Mechanism Coordinates Meiotic Prophase Events to Promote Crossover Assurance

PubMed Central

Deshong, Alison J.; Ye, Alice L.; Lamelza, Piero; Bhalla, Needhi

2014-01-01

Meiotic chromosome segregation relies on homologous chromosomes being linked by at least one crossover, the obligate crossover. Homolog pairing, synapsis and meiosis specific DNA repair mechanisms are required for crossovers but how they are coordinated to promote the obligate crossover is not well understood. PCH-2 is a highly conserved meiotic AAA+-ATPase that has been assigned a variety of functions; whether these functions reflect its conserved role has been difficult to determine. We show that PCH-2 restrains pairing, synapsis and recombination in C. elegans. Loss of pch-2 results in the acceleration of synapsis and homolog-dependent meiotic DNA repair, producing a subtle increase in meiotic defects, and suppresses pairing, synapsis and recombination defects in some mutant backgrounds. Some defects in pch-2 mutants can be suppressed by incubation at lower temperature and these defects increase in frequency in wildtype worms grown at higher temperature, suggesting that PCH-2 introduces a kinetic barrier to the formation of intermediates that support pairing, synapsis or crossover recombination. We hypothesize that this kinetic barrier contributes to quality control during meiotic prophase. Consistent with this possibility, defects in pch-2 mutants become more severe when another quality control mechanism, germline apoptosis, is abrogated or meiotic DNA repair is mildly disrupted. PCH-2 is expressed in germline nuclei immediately preceding the onset of stable homolog pairing and synapsis. Once chromosomes are synapsed, PCH-2 localizes to the SC and is removed in late pachytene, prior to SC disassembly, correlating with when homolog-dependent DNA repair mechanisms predominate in the germline. Indeed, loss of pch-2 results in premature loss of homolog access. Altogether, our data indicate that PCH-2 coordinates pairing, synapsis and recombination to promote crossover assurance. Specifically, we propose that the conserved function of PCH-2 is to destabilize pairing and/or recombination intermediates to slow their progression and ensure their fidelity during meiotic prophase. PMID:24762417

Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

PubMed

Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © 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.

The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive–behavioural therapy

PubMed Central

Murphy, Glynis H.; Shepstone, Lee; Wilson, Edward C.F.; Fowler, David; Heavens, David; Malovic, Aida; Russell, Alexandra; Rose, Alice; Mullineaux, Louise

2016-01-01

Background There is a growing interest in using cognitive–behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. Aims To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. Method Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. Results The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. Conclusions Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence. PMID:27703772

Protein substitute dosage in PKU: how much do young patients need?

PubMed

MacDonald, A; Chakrapani, A; Hendriksz, C; Daly, A; Davies, P; Asplin, D; Hall, K; Booth, I W

2006-07-01

The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance.

PubMed

Taniguchi-Fukatsu, Akiko; Yamanaka-Okumura, Hisami; Naniwa-Kuroki, Yuko; Nishida, Yuka; Yamamoto, Hironori; Taketani, Yutaka; Takeda, Eiji

2012-04-01

We previously suggested that the consumption of natto and viscous vegetables as part of a Japanese-style meal based on white rice (WR) reduced postprandial glucose and insulin levels in healthy subjects. The aim of the present study was to assess whether a single breakfast of natto and viscous vegetables or the same breakfast consumed for 2 weeks could improve glucose control, insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance (IGT). A total of eleven free-living subjects with IGT followed a randomised, crossover breakfast intervention for 2 weeks. The test meal included boiled WR with natto (viscous fermented soyabeans), Japanese yam and okra. The control meal included WR with non-viscous boiled soyabeans, potatoes and broccoli. Both meals contained comparable amounts of carbohydrate, fat, protein and fibre. The test meal reduced acute glucose and insulin responses compared to the control meal in the study participants. Insulin sensitivity was assessed using the composite insulin sensitivity index (CISI) after both the test and control meal periods. The test meal resulted in improvements in CISI compared to the baseline, whereas no significant changes were observed after the control meal period. Serum levels of both total and LDL-cholesterol were assessed before and after the test meal period and found to decrease significantly. There was also a tendency towards reduced serum malondialdehyde-modified LDL and N(ɛ)-carboxymethyllysine. No differences were observed in the measures of chronic glycaemic control. Thus, we conclude that a breakfast of natto and viscous vegetables consumed for 2 weeks improves insulin sensitivity, serum lipid and oxidative stress.

A randomised controlled trial to assess the effectiveness of a nurse-led palliative care intervention for HIV positive patients on antiretroviral therapy: recruitment, refusal, randomisation and missing data.

PubMed

Lowther, Keira; Higginson, Irene J; Simms, Victoria; Gikaara, Nancy; Ahmed, Aabid; Ali, Zipporah; Afuande, Gaudencia; Kariuki, Hellen; Sherr, Lorraine; Jenkins, Rachel; Selman, Lucy; Harding, Richard

2014-09-03

Despite the life threatening nature of an HIV diagnosis and the multidimensional problems experienced by this patient population during antiretroviral therapy, the effectiveness of a palliative care approach for HIV positive patients on ART is as yet unknown. A randomised controlled trial (RCT) was conducted in a sample of 120 HIV positive patients on ART in an urban clinic in Mombasa, Kenya. The intervention was a minimum of seven sessions of multidimensional, person-centred care, given by HIV nurses trained in the palliative care approach over a period of 5 months. Rates of recruitment and refusal, the effectiveness of the randomisation procedure, trial follow-up and attrition and extent of missing data are reported.120 patients (60 randomised to control arm, 60 randomised to intervention arm) were recruited over 5.5 months, with a refusal rate of 55.7%. During the study period, three participants died from cancer, three withdrew (two moved away and one withdrew due to time constraints). All of these patients were in the intervention arm: details are reported. There were five additional missing monthly interviews in both the control and intervention study arm, bringing the total of missing data to 26 data points (4.3%). The quality and implications of these data are discussed extensively and openly, including the effect of full and ethical consent procedures, respondent burden, HIV stigma, accurate randomisation, patient safety and the impact of the intervention. Data on recruitment randomisation, attrition and missing data in clinical trials should be routinely reported, in conjunction with the now established practice of publishing study protocols to enhance research integrity, transparency and quality. Transparency is especially important in cross cultural settings, in which the sources of funding and trial design are often not based in the country of data collection. Findings reported can be used to inform future RCTs in this area. Clinicaltrials.gov NCT01608802.

Rhombic-Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs.

PubMed

Ma, Zhipeng; Huang, Yunfei; Park, Seongsu; Kawai, Kentaro; Kim, Do-Nyun; Hirai, Yoshikazu; Tsuchiya, Toshiyuki; Yamada, Hirofumi; Tabata, Osamu

2018-01-01

DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency-modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic-shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one-third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3-turn crossover design rhombic-shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force-controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

PubMed

Heinisch, B B; Vila, G; Resl, M; Riedl, M; Dieplinger, B; Mueller, T; Luger, A; Pacini, G; Clodi, M

2012-05-01

B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. ClinicalTrials.gov: NCT01324739 The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

A combination of acid lactase from Aspergillus oryzae and yogurt bacteria improves lactose digestion in lactose maldigesters synergistically: A randomized, controlled, double-blind cross-over trial.

PubMed

de Vrese, Michael; Laue, Christiane; Offick, Birte; Soeth, Edlyn; Repenning, Frauke; Thoß, Angelika; Schrezenmeir, Jürgen

2015-06-01

Lactose digestion can be improved in subjects with impaired or completely absent intestinal lactase activity by administration of lactase preparations and particularly of acid lactase, which is active in the stomach, or by yogurt containing live lactic acid bacteria. It is the question, if lactose digestion can be further enhanced by combining these two approaches. We investigated in a randomised, placebo-controlled, double-blind, 5-arm crossover study on 24 lactose malabsorbers with variable degrees of lactase deficiency if different lactase preparations and freeze-dried yogurt culture affect gastrointestinal lactose digestion after consuming moderate amounts of lactose (12.5 g) by assessing hydrogen exhalation over 6 h. Furthermore, symptoms of lactose intolerance (excess gas production, abdominal pain, diarrhoea or nausea) were assessed using validated questionnaires. All preparations increased lactose digestion and reduced peak hydrogen exhalation by -27% (yogurt), -29/-33% (3300/9000 FCC(1) ((1) One FCC hydrolyses about 5 or 1.7-2.5 mg lactose in aquous solution or in (artificial) chyme, respectively, according to the FCC-III method of the Committee on Codex Specifications, Food and Nutrition Board, National Research Council. Food Chemicals Codex, 3rd edition. Washington, DC, National Academy Press, 1981 It cannot precisely be defined how much lactose can be hydrolysed in vivo by the consumption of a certain number of FCC units.) units acid lactase from Aspergillus oryzae) or -46%, respectively (3300 FCC units lactase plus yogurt culture combined), as compared with placebo (p < 0.001, Friedman test). The combination preparation had not only the strongest effect, but also showed the lowest variance in H(2)-exhalation values (less malabsorbers with no reduction of H(2)-exhalation) Apart from this, both the higher dose lactase and the combination preparation significantly reduced the symptoms most closely associated with H(2)-exhalation, namely flatulences and abdominal pain, respectively. The combined administration of freeze-dried yogurt cultures and acid lactase increases lactose digestion more than either freeze-dried yogurt cultures or acid lactase alone, and more lactose malabsorbers benefited from this effect. Copyright © 2014. Published by Elsevier Ltd.

Effect of β2-adrenergic receptor polymorphism on response to longacting β2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial

PubMed Central

Wechsler, Michael E.; Kunselman, Susan J.; Chinchilli, Vernon M; Bleecker, Eugene; Boushey, Homer A.; Calhoun, William J.; Ameredes, Bill T.; Castro, Mario; Craig, Timothy J; Denlinger, Loren; Fahy, John V.; Jarjour, Nizar; Kazani, Shamsah; Kim, Sophia; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F; Markezich, Amy; Martin, Richard J.; Permaul, Perdita; Peters, Stephen P; Ramsdell, Joe; Sorkness, Christine A.; Sutherland, E Rand; Szefler, Stanley J; Walter, Michael J; Wasserman, Stephen; Israel, Elliot

2010-01-01

Summary Background Combined long-acting β2-agonist and inhaled corticosteroid (LABA/ICS) therapy improves outcomes in many asthmatics. Some studies suggest that patients homozygous for arginine at the 16th amino-acid position of the β2 adrenergic receptor (B16 Arg/Arg) benefit less than those with B16 Gly/Gly. Methods In an NIH-funded, B16 genotype-stratified, prospective, randomized, double-blind, placebo-controlled, cross-over trial (www.ClinicalTrials.gov registration ID NCT00200967), we compared adding salmeterol or placebo to ICS in patients with moderate asthma, using AM PEF as the primary outcome. Findings After 18 weeks, Arg/Arg (n=42) and Gly/Gly (n=45) subjects had greater AM PEF with salmeterol than placebo, with no difference in improvement by genotype (Arg/Arg 21.4 (p<0.0001) vs. Gly/Gly 21.5 L/min (p<0.0001); 0.1 L/min difference between genotypes, 95% CI (−14.2, 14.4), p=0.99). In Gly/Gly subjects, methacholine PC20 (a secondary outcome) doubled when salmeterol was added to ICS (p<0.0001), but remained unchanged in Arg/Arg subjects (p=0.87) (1.32 doubling dose difference between genotypes (95%CI 0.43,2.21), p=0.0038). An exploratory posthoc subset analysis of African Americans showed that salmeterol improved the AM and PM PEF for the 8 Gly/Gly subjects (29 L/min, p=0.013 and 45 L/min, p= 0.0005, respectively) but not for the 9 Arg/Arg subjects (−12 L/min, p=0.57 and−2.2 L/min, p=0.92, respectively). Interpretation B16 Arg/Arg and Gly/Gly patients experience improved airway function with salmeterol added to moderate-dose ICS. While these data provide reassurance that in the general population these polymorphisms should not alter the use of LABA with moderate-dose ICS, the significance of the genotype-differentiated response in airway reactivity favoring Gly/Gly subjects and the post-hoc analysis in African Americans require further investigation. PMID:19932356

A randomised controlled cross-over double-blind pilot study protocol on THC:CBD oromucosal spray efficacy as an add-on therapy for post-stroke spasticity.

PubMed

Marinelli, Lucio; Balestrino, Maurizio; Mori, Laura; Puce, Luca; Rosa, Gian Marco; Giorello, Laura; Currà, Antonio; Fattapposta, Francesco; Serrati, Carlo; Gandolfo, Carlo; Abbruzzese, Giovanni; Trompetto, Carlo

2017-09-07

Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity. The neurophysiological assessment of the stretch reflex provides a precise and objective method to measure spasticity. We propose a novel study to understand if Sativex could be useful in reducing spasticity in stroke survivors and investigating tolerability and safety by accurate cardiovascular monitoring. We will recruit 50 patients with spasticity following stroke to take THC:CBD in a double-blind placebo-controlled cross-over study. Spasticity will be assessed with a numeric rating scale for spasticity, the modified Ashworth scale and with the electromyographical recording of the stretch reflex. The cardiovascular risk will be assessed prior to inclusion. Blood pressure, heart rate, number of daily spasms, bladder function, sleep disruption and adverse events will be monitored throughout the study. A mixed-model analysis of variance will be used to compare the stretch reflex amplitude between the time points; semiquantitative measures will be compared using the Mann-Whitney test (THC:CBD vs placebo) and Wilcoxon test (baseline vs treatment). The study was registered on the EudraCT database with number 2016-001034-10 and approved by both the Italian Medicines Agency (Agenzia Italiana del Farmaco) and local Ethics Committee 'Comitato Etico Regionale della Liguria'. Data will be made anonymous and uploaded to a open access repository. Results will be disseminated by presentations at national and international conferences and by publication in journals of clinical neuroscience and neurology. © 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.

Relaxation and guided imagery do not reduce stress, pain and unpleasantness for 11- to 12-year-old girls during vaccinations.

PubMed

Nilsson, Stefan; Forsner, Maria; Finnström, Berit; Mörelius, Evalotte

2015-07-01

Relaxation and guided imagery is a distraction technique known to reduce discomfort during paediatric medical procedures. We examined whether its use decreased the stress experienced by 11- to 12-year-old girls receiving the human papilloma virus vaccination, as well as the intensity and unpleasantness of any pain. A randomised crossover trial was conducted with 37 girls. During the first vaccination, each girl was randomised to receive either relaxation and guided imagery or standard care. They then received the other form of care during the second vaccination. Salivary cortisol was measured before each vaccination, and 30 minutes after it was administered. The girls reported pain intensity and pain unpleasantness before and directly after each vaccination and stress after each vaccination. On a group level, relaxation and guided imagery did not decrease cortisol levels, self-reported stress, pain intensity and pain unpleasantness. Salivary cortisol levels decreased significantly in both groups during the second vaccination. Relaxation and guided imagery did not prove beneficial during the vaccination of 11- to 12-year-old girls and is not recommended as a regular nursing intervention. However, further research is needed into effective techniques to help children who experience pain unpleasantness in connection with needle procedures. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Co-Phenylcaine Spray: can we improve the taste? A randomised, double-blind, crossover study.

PubMed

Bailey, S; Panizza, B; Cabot, P; Wallwork, B

2018-02-01

Co-Phenylcaine Forte is a nasal spray routinely prescribed by otolaryngologists in Australia. The taste of Co-Phenylcaine Forte is typically described as unpleasant. This study sought to improve the overall patient experience associated with Co-Phenylcaine Forte by generating a Co-Phenylcaine Forte formulation, referred to as Co-Phenylcaine Zest, which contains an added vanilla flavour and masking agent. Participants were randomised to receive two actuations of Co-Phenylcaine Forte in each nostril followed by two actuations of Co-Phenylcaine Zest, or vice versa. There was a 6-36-hour washout period between each treatment. After the administration of each spray, participants completed a questionnaire to rate various sensory attributes of each formulation on seven-point ordinal scales. Patients reported their overall formulation preference after receiving both treatments. A total of 86 participants completed the trial. Seventy-four per cent of patients preferred Co-Phenylcaine Zest, 21 per cent preferred Co-Phenylcaine Forte and 5 per cent had no preference (p < 0.001). The satisfaction score associated with Co-Phenylcaine Zest was 1.22 points greater than with Co-Phenylcaine Forte (p < 0.001). A novel formulation of Co-Phenylcaine Forte was created by adding a flavour and a masking agent; this formulation was preferred by most patients.

Comparison of non-invasive tear film stability measurement techniques.

PubMed

Wang, Michael Tm; Murphy, Paul J; Blades, Kenneth J; Craig, Jennifer P

2018-01-01

Measurement of tear film stability is commonly used to give an indication of tear film quality but a number of non-invasive techniques exists within the clinical setting. This study sought to compare three non-invasive tear film stability measurement techniques: instrument-mounted wide-field white light clinical interferometry, instrument-mounted keratoscopy and hand-held keratoscopy. Twenty-two subjects were recruited in a prospective, randomised, masked, cross-over study. Tear film break-up or thinning time was measured non-invasively by independent experienced examiners, with each of the three devices, in a randomised order, within an hour. Significant correlation was observed between instrument-mounted interferometric and keratoscopic measurements (p < 0.001) but not between the hand-held device and the instrument-mounted techniques (all p > 0.05). Tear film stability values obtained from the hand-held device were significantly shorter and demonstrated narrower spread than the other two instruments (all p < 0.05), while no significant differences were observed between the two instrument-mounted devices (all p > 0.05). Good clinical agreement exists between the instrument-mounted interferometric and keratoscopic measurements but not between the hand-held device and either of the instrument-mounted techniques. The results highlight the importance of specifying the instrument employed to record non-invasive tear film stability. © 2017 Optometry Australia.

ARIX: a randomised trial of acupuncture v oral care sessions in patients with chronic xerostomia following treatment of head and neck cancer.

PubMed

Simcock, R; Fallowfield, L; Monson, K; Solis-Trapala, I; Parlour, L; Langridge, C; Jenkins, V

2013-03-01

Radiation treatment of head and neck cancer can cause chronic xerostomia which impairs patients' quality of life. The study reported here examined the efficacy of acupuncture in alleviating xerostomia symptoms especially dry mouth. A total of 145 patients with chronic radiation-induced xerostomia >18 months after treatments were recruited from seven UK cancer centres. The study employed a randomised crossover design with participants receiving two group sessions of oral care education and eight of acupuncture using standardised methods. Patient-reported outcome (PROs) measures were completed at baseline and weeks 5, 9, 13, 17, and 21. The primary outcome was improvement in dry mouth. saliva measurements were also carried out. Acupuncture compared with oral care, produced significant reductions in patient reports of severe dry mouth (OR = 2.01, P = 0.031) sticky saliva (OR = 1.67, P = 0.048), needing to sip fluids to swallow food (OR = 2.08, P = 0.011) and in waking up at night to drink (OR = 1.71, P = 0.013). There were no significant changes in either stimulated or unstimulated saliva measurements over time. Eight sessions of weekly group acupuncture compared with group oral care education provide significantly better relief of symptoms in patients suffering from chronic radiation-induced xerostomia.

Individual versus interprofessional team performance in formulating care transition plans: A randomised study of trainees from five professional groups.

PubMed

Farrell, Timothy W; Supiano, Katherine P; Wong, Bob; Luptak, Marilyn K; Luther, Brenda; Andersen, Troy C; Wilson, Rebecca; Wilby, Frances; Yang, Rumei; Pepper, Ginette A; Brunker, Cherie P

2018-05-01

Health professions trainees' performance in teams is rarely evaluated, but increasingly important as the healthcare delivery systems in which they will practice move towards team-based care. Effective management of care transitions is an important aspect of interprofessional teamwork. This mixed-methods study used a crossover design to randomise health professions trainees to work as individuals and as teams to formulate written care transition plans. Experienced external raters assessed the quality of the written care transition plans as well as both the quality of team process and overall team performance. Written care transition plan quality did not vary between individuals and teams (21.8 vs. 24.4, respectively, p = 0.42). The quality of team process did not correlate with the quality of the team-generated written care transition plans (r = -0.172, p = 0.659). However, there was a significant correlation between the quality of team process and overall team performance (r = 0.692, p = 0.039). Teams with highly engaged recorders, performing an internal team debrief, had higher-quality care transition plans. These results suggest that high-quality interprofessional care transition plans may require advance instruction as well as teamwork in finalising the plan.

Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial

PubMed Central

Aggestrup, Louise Mosborg; Hestbech, Mie Sara; Siersma, Volkert; Pedersen, Jesper Holst

2012-01-01

Objective To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. Method The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. Results There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales ‘anxiety’, ‘behaviour’, ‘dejection’, ‘self-blame’, ‘focus on airway symptoms’ and ‘introvert’, with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Conclusions Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants—both the participants in the screen group and the control group. This negative impact was greatest for the control group. PMID:22382119

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero, One and Five in India: A Decomposition Analysis

PubMed Central

Dubey, Manisha

2015-01-01

Objectives Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover. Methods We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981–2009 for 16 Indian states by sex (comprising of India’s 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover. Findings India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women). Conclusions For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1–59 months in high child mortality areas can help India to attain this crossover early. PMID:26683617

Outcomes and Process in Reading Tutoring

ERIC Educational Resources Information Center

Topping, K. J.; Thurston, A.; McGavock, K.; Conlin, N.

2012-01-01

Background: Large-scale randomised controlled trials are relatively rare in education. The present study approximates to, but is not exactly, a randomised controlled trial. It was an attempt to scale up previous small peer tutoring projects, while investing only modestly in continuing professional development for teachers. Purpose: A two-year…

Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study

PubMed Central

Glenton, Claire; Oxman, Andrew D

2009-01-01

Objective To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Design Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Data sources Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Methods Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. Results 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Conclusions Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings. PMID:19744976

Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review.

PubMed

Deodati, Annalisa; Cianfarani, Stefano

2011-03-11

To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. Systematic review. Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomised controlled trials from 1985 to April 2010. Height in adulthood (standard deviation score) and overall gain in height (SD score) from baseline measurement in childhood. Randomised and non-randomised controlled trials with height measurements for adults. Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was <1.5 cm/year or bone age was 15 years in females and 16 years in males. Three randomised controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SD score (about 4 cm). The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score (about 3 cm). Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders.

Establishing the effectiveness, cost-effectiveness and student experience of a Simulation-based education Training program On the Prevention of Falls (STOP-Falls) among hospitalised inpatients: a protocol for a randomised controlled trial

PubMed Central

Williams, Cylie; Kiegaldie, Debra; Kaplonyi, Jessica; Haines, Terry

2016-01-01

Introduction Simulation-based education (SBE) is now commonly used across health professional disciplines to teach a range of skills. The evidence base supporting the effectiveness of this approach for improving patient health outcomes is relatively narrow, focused mainly on the development of procedural skills. However, there are other simulation approaches used to support non-procedure specific skills that are in need of further investigation. This cluster, cross-over randomised controlled trial with a concurrent economic evaluation (cost per fall prevented) trial will evaluate the effectiveness, cost-effectiveness and student experience of health professional students undertaking simulation training for the prevention of falls among hospitalised inpatients. This research will target the students within the established undergraduate student placements of Monash University medicine, nursing and allied health across Peninsula Health acute and subacute inpatient wards. Methods and analysis The intervention will train the students in how to provide the Safe Recovery program, the only single intervention approach demonstrated to reduce falls in hospitals. This will involve redevelopment of the Safe Recovery program into a one-to-many participant SBE program, so that groups of students learn the communication skills and falls prevention knowledge necessary for delivery of the program. The primary outcome of this research will be patient falls across participating inpatient wards, with secondary outcomes including student satisfaction with the SBE and knowledge gain, ward-level practice change and cost of acute/rehabilitation care for each patient measured using clinical costing data. Ethics and dissemination The Human Research Ethics Committees of Peninsula Health (LRR/15/PH/11) and Monash University (CF15/3523-2015001384) have approved this research. The participant information and consent forms provide information on privacy, storage of results and dissemination. Registration of this trial has been completed with the Australian and New Zealand Clinical Trials Registry: ACTRN12615000817549. This study protocol has been prepared according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. Trial registration number ACTRN12615000817549; Pre-results. PMID:27256087

Swim drink study: a randomised controlled trial of during-exercise rehydration and swimming performance.

PubMed

Briars, Graham L; Gordon, Gillian Suzanne; Lawrence, Andrew; Turner, Andrew; Perry, Sharon; Pillbrow, Dan; Walston, Florence Einstein; Molyneux, Paul

2017-01-01

To determine whether during-exercise rehydration improves swimming performance and whether sports drink or water have differential effects on performance. Randomised controlled multiple crossover trial. A UK competitive swimming club. 19 club-level competitive swimmers, median age (range) 13 (11-17) years. Subjects were scheduled to drink ad libitum commercial isotonic sports drink (3.9 g sugars and 0.13 g salt per 100 mL) or water (three sessions each) or no drink (six sessions) in the course of twelve 75 min training sessions, each of which was followed by a 30 min test set of ten 100 m maximum-effort freestyle sprints each starting at 3 min intervals. Times for the middle 50 m of each sprint measured using electronic timing equipment in a Federation Internationale de Natation (FINA)-compliant six-lane 25 m competition swimming pool. Software-generated individual random session order in sealed envelopes. Analysis subset of eight sessions randomly selected by software after data collection completed. Participants blind to drink allocation until session start. In the analysis data set of 1118 swims, there was no significant difference between swim times for drinking and not drinking nor between drinking water or a sports drink. Mean (SEM) 50 m time for no-drink swims was 38.077 (0.128) s and 38.105 (0.131) s for drink swims, p=0.701. Mean 50 m times were 38.031 (0.184) s for drinking sports drink and 38.182 (0.186) s for drinking water, p=0.073. Times after not drinking were 0.027 s faster than after drinking (95% CI 0.186 s faster to 0.113 s slower). Times after drinking sports drink were 0.151 s faster than after water (95% CI 0.309 s faster to 0.002 s slower). Mean (SEM) dehydration from exercise was 0.42 (0.11)%. Drinking water or sports drink over 105 min of sustained effort swimming training does not improve swimming performance. ISRCTN: 49860006.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Control of oral malodour by dentifrices measured by gas chromatography.

PubMed

Newby, Evelyn E; Hickling, Jenneth M; Hughes, Francis J; Proskin, Howard M; Bosma, Marylynn P

2008-04-01

To evaluate the effect of toothpaste treatments on levels of oral volatile sulphur compounds (VSCs) measured by gas chromatography in two clinical studies. These were blinded, randomised, controlled, crossover studies with 16 (study A) or 20 (study B) healthy volunteers between the ages of 19-54. Study A: breath samples were collected at baseline, immediately and lhr after brushing. Four dentifrices (Zinc A, Zinc B, commercially available triclosan dentifrice and zinc free control) were evaluated. Study B: breath samples were collected at baseline, immediately, 1, 2, 3 and 7 hours after treatment. Subjects consumed a light breakfast then provided an additional breath sample between baseline assessment and treatment. Two dentifrices (gel-to-foam and a commercially available triclosan dentrifrice) were evaluated. Breath samples were collected in syringes and analysed for VSCs (hydrogen sulphide, methyl mercaptan and Total VSCs) utilising gas chromatography (GC) with flame photometric detection. Study A: immediately after treatment, a statistically significant reduction in VSCs from baseline was observed for Zinc A product only. A statistically significant reduction in VSCs from baseline was observed after 1 hour for all products. Both zinc products exhibited a significantly greater reduction from baseline VSCs than Colgate Total and Control at all time points. Study B: a statistically significant reduction in VSCs from baseline was observed at all time points for both products. The gel-to-foam product exhibited significantly greater reduction from baseline Total VSC concentration than Colgate Total at all time points from 1 hour post-treatment. Control of oral malodour by toothpaste treatment, evaluated as VSC levels using GC, has been demonstrated. Zinc is effective at reducing VSCs and the efficacy of zinc is formulation dependent. A gel-to-foam dentifrice was more effective at reducing VSCs than Colgate Total up to 7 hours.

The effects of bulking, viscous and gel-forming dietary fibres on satiation.

PubMed

Wanders, Anne J; Jonathan, Melliana C; van den Borne, Joost J G C; Mars, Monica; Schols, Henk A; Feskens, Edith J M; de Graaf, Cees

2013-04-14

The objective was to determine the effects of dietary fibre with bulking, viscous and gel-forming properties on satiation, and to identify the underlying mechanisms. We conducted a randomised crossover study with 121 men and women. Subjects were healthy, non-restrained eaters, aged 18-50 years and with normal BMI (18.5-25 kg/m²). Test products were cookies containing either: no added fibre (control), cellulose (bulking, 5 g/100 g), guar gum (viscous, 1.25 g/100 g and 2.5 g/100 g) or alginate (gel forming, 2.5 g/100 g and 5 g/100 g). Physico-chemical properties of the test products were confirmed in simulated upper gastrointestinal conditions. In a cinema setting, ad libitum intake of the test products was measured concurrently with oral exposure time per cookie by video recording. In a separate study with ten subjects, 4 h gastric emptying rate of a fixed amount of test products was assessed by ¹³C breath tests. Ad libitum energy intake was 22 % lower for the product with 5 g/100 g alginate (3.1 (sd 1.6) MJ) compared to control (4.0 (sd 2.2) MJ, P< 0.001). Intake of the other four products did not differ from control. Oral exposure time for the product with 5 g/100 g alginate (2.3 (sd 1.9) min) was 48 % longer than for control (1.6 (sd 0.9) min, P= 0.01). Gastric emptying of the 5 g/100 g alginate product was faster compared to control (P< 0.05). We concluded that the addition of 5 g/100 g alginate (i.e. gel-forming fibre) to a low-fibre cookie results in earlier satiation. This effect might be due to an increased oral exposure time.

Vitamin D supplementation for cystic fibrosis.

PubMed

Ferguson, Janet H; Chang, Anne B

2012-04-18

Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in CF. To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the CF population. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 February 2012. Randomised and quasi-randomised controlled trials of vitamin D supplementation compared to placebo in the CF population regardless of exocrine pancreatic function. Both authors independently assessed the 'risk of bias' of each included trial and extracted outcome data (from published trial information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events. Three studies are included, although only data from two were available (41 adults and children with CF). One of these studies compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The other (abstract only) compared supplemental 1g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1g calcium and placebo in a double-blind randomised cross-over trial; only 11 children (vitamin D and placebo groups) after six-months supplementation are included; inclusion criteria, pancreatic sufficiency or disease status of participants are not defined. There were no significant differences in primary or secondary outcomes in either study. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (eg severity of lung disease, growth and nutrition, pancreatic sufficiency). There were no adverse events in either study. The third study (abstract only) compared daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults, only pre-intervention data were available. There is no evidence of benefit or harm in the limited number of small-sized published trials. Adherence to relevant CF guidelines on vitamin D should be considered until further evidence is available.

Effects of sodium restriction and hydrochlorothiazide on RAAS blockade efficacy in diabetic nephropathy: a randomised clinical trial.

PubMed

Kwakernaak, Arjan J; Krikken, Jan A; Binnenmars, S Heleen; Visser, Folkert W; Hemmelder, Marc H; Woittiez, Arend-Jan; Groen, Henk; Laverman, Gozewijn D; Navis, Gerjan

2014-05-01

Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide, separately and in combination, added to RAAS blockade on residual albuminuria in patients with type 2 diabetic nephropathy. In this multicentre, double-blind, placebo-controlled, crossover randomised trial, we included patients with type 2 diabetic nephropathy. Main entry criteria were microalbuminaria or macroalbuminuria, and creatinine clearance of 30 mL/min or higher with less than 6 mL/min decline in the previous year. We tested the separate and combined effects of sodium restriction (dietary counselling in the outpatient setting) and hydrochlorothiazide (50 mg daily), added to standardised maximal angiotensin-converting enzyme (ACE) inhibition (lisinopril 40 mg daily), on albuminuria (primary endpoint). Patients were given hydrochlorothiazide (50 mg per day) or placebo during four treatment periods of 6 weeks. Both treatments were combined with regular sodium diet or sodium restriction (target sodium intake 50 mmol Na(+) per day). The 6-week treatment periods were done consecutively in a random order. Patients were randomised in blocks of two patients. The trial was analysed by intention to treat. The trial is registered with TrialRegister.nl, number 2366. Of 89 eligible patients, 45 were included in the study. Both sodium restriction and hydrochlorothiazide significantly reduced albuminuria, irrespective of treatment sequence. Residual geometric mean albuminuria with baseline treatment was 711 mg per day (95% CI 485-1043); it was significantly reduced by sodium restriction (393 mg per day [258-599], p=0·0002), by hydrochlorothiazide (434 mg per day [306-618], p=0·0003), and to the greatest extent by their combination (306 mg per day [203-461], p<0·0001). Orthostatic complaints were present in two patients (4%) during baseline treatment, five (11%) during addition of sodium restriction, five (11%) during hydrochlorothiazide treatment, and 12 (27%) during combination treatment. No serious adverse events occurred. We conclude that sodium restriction is an effective non-pharmacological intervention to increase RAAS blockade efficacy in type 2 diabetic nephropathy. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

A randomised titrated crossover study comparing two oral appliances in the treatment for mild to moderate obstructive sleep apnoea/hypopnoea syndrome.

PubMed

Zhou, J; Liu, Y H

2012-12-01

The objective of this study was to compare the efficiency of two oral appliances in patients with mild to moderate obstructive sleep apnoea/hypopnoea syndrome (OSAHS) by the analysis of objective and subjective evaluations and measurement of upper airway parameter. A randomised crossover design trial was carried out on 16 patients with OSAHS. Two different types of oral appliances were tested in each patient, a one-piece monoblock and the SILENT NITE(®) (GlideWell Laboratories, Newport Beach, CA, USA), a two-piece appliance. Each oral appliance needed to be worn for two 3-month periods separated by a 2-week wash-out period in between. The objective and subjective efficiency and upper airway parameters associated with the oral appliances were assessed. One-way analysis of variance (anova) test was performed to compare the changes in upper airway morphology and the treatment efficiency between the appliances. The monoblock and SILENT NITE(®) (GlideWell Laboratories) appliances reduced Apnoea Hypopnoea Index (AHI) from 26·38 ± 4·13 to 7·58 ± 2·28 (P < 0·001) and 8·87 ± 2·88 (P < 0·001), respectively. The monoblock appliance was statistically more efficient in reducing AHI and Apnoea Index (AI) than the SILENT NITE(®) (GlideWell Laboratories) (P < 0·05). The scores on Epworth's Sleepiness Scale (ESS) and Snoring Scale (SS) were improved significantly by both appliances. The upper airway spaces showed considerable enlargement by both mandibular advancement appliances (MAAs) (P < 0·05), while no significant differences were found between the two appliances (P > 0·05). Both MAAs showed good efficacy in the treatment for mild to moderate OSAHS. Use of the monoblock appliance should be considered when patients with OSAHS choose MAA treatment, as it was more efficient in reducing the AHI and AI compared to the two-piece appliance and was preferred by most patients. Long-term efficiency should be evaluated in future prospective studies. © 2012 Blackwell Publishing Ltd.

360° Operative Videos: A Randomised Cross-Over Study Evaluating Attentiveness and Information Retention.

PubMed

Harrington, Cuan M; Kavanagh, Dara O; Wright Ballester, Gemma; Wright Ballester, Athena; Dicker, Patrick; Traynor, Oscar; Hill, Arnold; Tierney, Sean

2017-11-06

Although two-dimensional (2D) and three-dimensional videos have traditionally provided foundations for reviewing operative procedures, the recent 360º format may provide new dimensions to surgical education. This study sought to describe the production of a high quality 360º video for an index-operation (augmented with educational material), while evaluating for variances in attentiveness, information retention, and appraisal compared to 2D. A 6-camera synchronised array (GoPro Omni, [California, United States]) was suspended inverted and recorded an elective laparoscopic cholecystectomy in 2016. A single-blinded randomised cross-over study was performed to evaluate this video in 360º vs 2D formats. Group A experienced the 360º video using Samsung (Suwon, South-Korea) GearVR virtual-reality headsets, followed by the 2D experience on a 75-inch television. Group B were reversed. Each video was probed at designated time points for engagement levels and task-unrelated images or thoughts. Alternating question banks were administered following each video experience. Feedback was obtained via a short survey at study completion. The New Academic and Education Building (NAEB) in Dublin, Royal College of Surgeons in Ireland, July 2017. Preclinical undergraduate students from a medical university in Ireland. Forty students participated with a mean age of 23.2 ± 4.5 years and equal sex involvement. The 360º video demonstrated significantly higher engagement (p < 0.01) throughout the experience and lower task-unrelated images or thoughts (p < 0.01). Significant variances in information retention between the 2 groups were absent (p = 0.143) but most (65%) reported the 360º video as their learning platform of choice. Mean appraisal levels for the 360º platform were positive with mean responses of >8/10 for the platform for learning, immersion, and entertainment. This study describes the successful development and evaluation of a 360º operative video. This new video format demonstrated significant engagement and attentiveness benefits compared to traditional 2D formats. This requires further evaluation in the field of technology enhanced learning. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Levofloxacin-based and clarithromycin-based triple therapies as first-line and second-line treatments for Helicobacter pylori infection: a randomised comparative trial with crossover design.

PubMed

Liou, Jyh-Ming; Lin, Jaw-Town; Chang, Chi-Yang; Chen, Mei-Jyh; Cheng, Tsu-Yao; Lee, Yi-Chia; Chen, Chien-Chuan; Sheng, Wang-Huei; Wang, Hsiu-Po; Wu, Ming-Shiang

2010-05-01

The efficacy of a levofloxacin-based regimen as the first-line treatment and a clarithromycin-based regimen as the second-line treatment for Helicobacter pylori infection remains unknown. The aim of this study was to assess the eradication rates of these two regimens using different administration sequences. Eligible patients were randomised to receive LAL: levofloxacin (750 mg once a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days, or CAL: clarithromycin (500 mg twice a day), amoxicillin (1000 mg twice a day) and lansoprazole (30 mg twice a day) for 7 days. Patients with positive [(13)C]urea breath test after treatment were retreated with the rescue regimen in a crossover manner for 10 days. When used as first-line treatment (n=432), the eradication rates of LAL (n=217) and CAL (n=215) were 74.2 and 83.7% (p=0.015) in the intent-to-treat (ITT) analysis, and 80.1 and 87.4% (p=0.046) in the per-protocol (PP) analysis, respectively. When used as second-line treatment, the eradication rates of LAL (n=26) and CAL (n=40) were 76.9 and 60% (p=0.154) in the ITT analysis, and 80 and 61.5% (p=0.120) in the PP analysis, respectively. The overall eradication rates of CAL followed by LAL were better than the reverse sequence in both the ITT analysis (93% vs 85.3%, p=0.01) and the PP analysis (97.6% vs 92.5%, p=0.019). The eradication rate was significantly lower in the presence of levofloxacin resistance in the LAL group (50% vs 84.4%, p=0.018) and clarithromycin resistance in the CAL group (44.4% vs 90.7%, p=0.002). CAL achieved a higher eradication rate than LAL as the first-line treatment, but not as the second-line treatment. The strategy of using CAL as the initial treatment and LAL as the rescue regimen achieved higher eradication rates than the reverse sequence.

Effects of superficial heating and insulation on walking speed in people with hereditary and spontaneous spastic paraparesis: A randomised crossover study.

PubMed

Denton, Amanda L; Hough, Alan D; Freeman, Jennifer A; Marsden, Jonathan F

2018-03-01

Cooling of the lower limb in people with Hereditary and Spontaneous Spastic Paraparesis (pwHSSP) has been shown to affect walking speed and neuromuscular impairments. The investigation of practical strategies, which may help to alleviate these problems is important. The potential of superficial heat to improve walking speed has not been explored in pwHSSP. Primary objective was to explore whether the application of superficial heat (hot packs) to lower limbs in pwHSSP improves walking speed. Secondary objective was to explore whether wearing insulation after heating would prolong any benefits. A randomised crossover study design with 21 pwHSSP. On two separate occasions two hot packs and an insulating wrap (Neo-G™) were applied for 30minutes to the lower limbs of pwHSSP. On one occasion the insulating wrap was maintained for a further 30minutes and on the other occasion it was removed. Measures of temperature (skin, room and core), walking speed (10 metre timed walk) and co-ordination (foot tap time) were taken at baseline (T1), after 30 mins (T2) and at one hour (T3). All 21 pwHSSP reported increased lower limb stiffness and decreased walking ability when their legs were cold. After thirty minutes of heating, improvements were seen in walking speed (12.2%, P<0.0001, effect size 0.18) and foot tap time (21.5%, P<0.0001, effect size 0.59). Continuing to wear insulation for a further 30minutes gave no additional benefit; with significant improvements in walking speed maintained at one hour (9.9%, P>0.001) in both conditions. Application of 30minutes superficial heating moderately improved walking speed in pwHSSP with effects maintained at 1hour. The use of hot packs applied to lower limbs should be the focus of further research for the clinical management of pwHSSP who report increased stiffness of limbs in cold weather and do not have sensory deficits. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Propensity score matching and persistence correction to reduce bias in comparative effectiveness: the effect of cinacalcet use on all-cause mortality.

PubMed

Gillespie, Iain A; Floege, Jürgen; Gioni, Ioanna; Drüeke, Tilman B; de Francisco, Angel L; Anker, Stefan D; Kubo, Yumi; Wheeler, David C; Froissart, Marc

2015-07-01

The generalisability of randomised controlled trials (RCTs) may be limited by restrictive entry criteria or by their experimental nature. Observational research can provide complementary findings but is prone to bias. Employing propensity score matching, to reduce such bias, we compared the real-life effect of cinacalcet use on all-cause mortality (ACM) with findings from the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) RCT in chronic haemodialysis patients. Incident adult haemodialysis patients receiving cinacalcet, recruited in a prospective observational cohort from 2007-2009 (AROii; n = 10,488), were matched to non-exposed patients regardless of future exposure status. The effect of treatment crossover was investigated with inverse probability of censoring weighted and lag-censored analyses. EVOLVE ACM data were analysed largely as described for the primary composite endpoint. AROii patients receiving cinacalcet (n = 532) were matched to 1790 non-exposed patients. The treatment effect of cinacalcet on ACM in the main AROii analysis (hazard ratio 1.03 [95% confidence interval (CI) 0.78-1.35]) was closer to the null than for the Intention to Treat (ITT) analysis of EVOLVE (0.94 [95%CI 0.85-1.04]). Adjusting for non-persistence by 0- and 6-month lag-censoring and by inverse probability of censoring weight, the hazard ratios in AROii (0.76 [95%CI 0.51-1.15], 0.84 [95%CI 0.60-1.18] and 0.79 [95%CI 0.56-1.11], respectively) were comparable with those of EVOLVE (0.82 [95%CI 0.67-1.01], 0.83 [95%CI 0.73-0.96] and 0.87 [95%CI 0.71-1.06], respectively). Correcting for treatment crossover, we observed results in the 'real-life' setting of the AROii observational cohort that closely mirrored the results of the EVOLVE RCT. Persistence-corrected analyses revealed a trend towards reduced ACM in haemodialysis patients receiving cinacalcet therapy. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of lingual nerve block on burning mouth syndrome (stomatodynia): a randomized crossover trial.

PubMed

Grémeau-Richard, Christelle; Dubray, Claude; Aublet-Cuvelier, Bruno; Ughetto, Sylvie; Woda, Alain

2010-04-01

Burning mouth syndrome (stomatodynia) is associated with changes of a neuropathic nature the main location of which, peripheral or central, remains unknown. A randomised, double-blind crossover design was used to investigate the effects of lingual nerve block on spontaneous burning pain and a possible correlation with the effects of topical clonazepam, the patient's response to a psychological questionnaire, and the taste and heat thresholds. The spontaneous burning was measured with a visual analogue scale (VAS) just before and 15 min after injection. The decreases in VAS score after lidocaine or saline injection were not significantly different (2.7+/-3.9 and 2.0+/-2.6, respectively; n=20). However, two groups of patients could be identified: in a "peripheral group" (n=10) the VAS decrease due to lingual nerve injection was 4.3+/-3.1cm after lidocaine and 0.9+/-0.3 cm after saline (p=0.02). In a "central group" (n=7), there were an increase in pain intensity score (-0.8+/-2.6 cm) after lidocaine and a decrease (1.5+/-3.0 cm) after saline (p=0.15). An increase in the hospital anxiety and depression (HAD) score and a decreased taste sensitivity and heat pain threshold of painful oral area were seen in patients compared with age-and-sex-matched controls (p<0.05). Topical clonazepam treatment tended to be more effective (p=0.07) and HAD score lower (p<0.03) in the peripheral than in the central group. These results suggest that the neuropathic disorder associated with stomatodynia may be predominantly peripheral, central or mixed depending on the individual. Topical application of clonazepam and HAD may serve as indicators of which mechanism is dominating. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

A systematic review of training programmes for recruiters to randomised controlled trials.

PubMed

Townsend, Daisy; Mills, Nicola; Savović, Jelena; Donovan, Jenny L

2015-09-28

Recruitment to randomised controlled trials (RCTs) is often difficult. Clinician related factors have been implicated as important reasons for low rates of recruitment. Clinicians (doctors and other health professionals) can experience discomfort with some underlying principles of RCTs and experience difficulties in conveying them positively to potential trial participants. Recruiter training has been suggested to address identified problems but a synthesis of this research is lacking. The aim of our study was to systematically review the available evidence on training interventions for recruiters to randomised trials. Studies that evaluated training programmes for trial recruiters were included. Those that provided only general communication training not linked to RCT recruitment were excluded. Data extraction and quality assessment were completed by two reviewers independently, with a third author where necessary. Seventeen studies of 9615 potentially eligible titles and abstracts were included in the review: three randomised controlled studies, two non-randomised controlled studies, nine uncontrolled pre-test/post-test studies, two qualitative studies, and a post-training questionnaire survey. Most studies were of moderate or weak quality. Training programmes were mostly set within cancer trials, and usually consisted of workshops with a mix of health professionals over one or two consecutive days covering generic and trial specific issues. Recruiter training programmes were well received and some increased recruiters' self-confidence in communicating key RCT concepts to patients. There was, however, little evidence that this training increased actual recruitment rates or patient understanding, satisfaction, or levels of informed consent. There is a need to develop recruiter training programmes that can lead to improved recruitment and informed consent in randomised trials.

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

PubMed

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

2016-04-01

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

Outcomes in a Randomised Controlled Trial of Mathematics Tutoring

ERIC Educational Resources Information Center

Topping, K. J.; Miller, D.; Murray, P.; Henderson, S.; Fortuna, C.; Conlin, N.

2011-01-01

Background: Large-scale randomised controlled trials (RCT) are relatively rare in education. The present study was an attempt to scale up previous small peer tutoring projects, while investing only modestly in continuing professional development for teachers. Purpose: A two-year RCT of peer tutoring in mathematics was undertaken in one local…

Can exercise improve self esteem in children and young people? A systematic review of randomised controlled trials

PubMed Central

Ekeland, E; Heian, F; Hagen, K; Coren, E

2005-01-01

Twenty three randomised controlled trials were analysed. A synthesis of several small, low quality trials indicates that exercise may have short term beneficial effects on self esteem in children and adolescents. However, high quality research on defined populations with adequate follow up is needed. PMID:16244186

Implementing Randomised Control Trials in Open and Distance Learning: A Feasibility Study

ERIC Educational Resources Information Center

Herodotou, Christothea; Heiser, Sarah; Rienties, Bart

2017-01-01

Randomised control trials (RCTs) are an evidence-based research approach which has not yet been adopted and widely used in open and distance education to inform educational policy and practice. Despite the challenges entailed in their application, RCTs hold the power to robustly evaluate the effects of educational interventions in distance…

Reading and Language Intervention for Children at Risk of Dyslexia: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Duff, Fiona J.; Hulme, Charles; Grainger, Katy; Hardwick, Samantha J.; Miles, Jeremy N. V.; Snowling, Margaret J.

2014-01-01

Background: Intervention studies for children at risk of dyslexia have typically been delivered preschool, and show short-term effects on letter knowledge and phoneme awareness, with little transfer to literacy. Methods: This randomised controlled trial evaluated the effectiveness of a reading and language intervention for 6-year-old children…

Elementary Science Teachers' Integration of Engineering Design into Science Instruction: Results from a Randomised Controlled Trial

ERIC Educational Resources Information Center

Maeng, Jennifer L.; Whitworth, Brooke A.; Gonczi, Amanda L.; Navy, Shannon L.; Wheeler, Lindsay B.

2017-01-01

This randomised controlled trial used a mixed-methods approach to investigate the frequency and how elementary teachers integrated engineering design (ED) principles into their science instruction following professional development (PD). The ED components of the PD were aligned with Cunningham and Carlsen's [(2014). "Teaching engineering…

Skills Training to Avoid Inadvertent Plagiarism: Results from a Randomised Control Study

ERIC Educational Resources Information Center

Newton, Fiona J.; Wright, Jill D.; Newton, Joshua D.

2014-01-01

Plagiarism continues to be a concern within academic institutions. The current study utilised a randomised control trial of 137 new entry tertiary students to assess the efficacy of a scalable short training session on paraphrasing, patch writing and plagiarism. The results indicate that the training significantly enhanced students' overall…

Washout policies in long-term indwelling urinary catheterisation in adults.

PubMed

Hagen, Suzanne; Sinclair, Lesley; Cross, Stephen

2010-03-17

People requiring long-term bladder draining with an indwelling catheter can experience catheter blockage. Regimens involving different solutions can be used to washout catheters with the aim of preventing blockage. To determine if certain washout regimens are better than others in terms of effectiveness, acceptability, complications, quality of life and economics for the management of long-term indwelling urinary catheterisation in adults. We searched the Cochrane Incontinence Group Specialised Trials Register, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, CINAHL and EMBASE (searches last updated April 2009). Additionally, we examined all reference lists of identified trials. All randomised and quasi-randomised trials comparing catheter washout policies (e.g. washout versus no washout, different washout solutions, frequency, duration, volume, concentration, method of administration) in adults (16 years and above) in any setting (i.e. hospital, nursing/residential home, community) with an indwelling urethral or suprapubic catheter for more than 28 days. Data were extracted by three reviewers independently and compared. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook. If the data in trials were not fully reported, clarification was sought from the authors. For categorical outcomes, the numbers reporting an outcome were related to the numbers at risk in each group to derive an risk ratio (RR). For continuous outcomes, means and standard deviations were used to derive weighted mean differences (WMD). No meta-analysis of study results was possible. Five trials met the inclusion criteria involving 242 patients (132 completed) in two cross-over and three parallel-group randomised controlled trials. Only three of the eight pre-stated comparisons were addressed in these trials. Some trials addressed more than one comparison (e.g. washout versus no washout and one type of washout solution versus another). The analyses reported for the two cross-over trials were inappropriate as they were based on differences between groups rather than differences within individuals receiving sequential interventions. Two parallel-group trials had limited value: one combined results for suprapubic and urethral catheters and one had data on only four participants. Only one trial was free of significant methodological limitations, but its sample size was small.Three trials compared no washout with one or more washout solution (saline or acidic solutions) and authors tended to conclude no difference in clinical outcomes between washout and no washout. In the one trial which had data of sufficient quality to allow interpretation, no difference was detected between washout and no washout groups in the rate of symptomatic urinary tract infection or time to first catheter change. Three trials compared different types of solution: saline versus acidic solutions (two trials); saline versus acidic solution versus antibiotic solution (one trial). Authors tended to report no difference between different washout solutions but the data were too few to support their conclusions. The one trial which warranted consideration concluded no difference between saline and an acidic solution in terms of symptomatic urinary tract infections or time to first catheter change. The data from five trials comparing differing washout policies were sparse and trials were generally of poor quality or poorly reported. The evidence was too scanty to conclude whether or not washouts were beneficial. In the first instance we require further rigorous, high quality trials with adequate power to detect any benefit from washout being performed as opposed to none. Then trials comparing different washout solutions, washout volumes, frequencies/timings and routes of administration are needed.

Beta-blocker therapy for tremor in Parkinson's disease.

PubMed

Crosby, N J; Deane, K H O; Clarke, C E

2003-01-01

The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease. Electronic searches of MEDLINE, EMBASE, SCISEARCH, BIOSIS, GEROLIT, OLDMEDLINE, LILACS, MedCarib, PASCAL, JICST-EPLUS, RUSSMED, DISSERTATION ABSTRACTS, SIGLE, ISI-ISTP, Aslib Index to Theses, The Cochrane Controlled Trials Register, Clinicaltrials.gov, metaRegister of Controlled Trials, NIDRR, NRR and CENTRAL were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of beta-blockers were contacted. Randomised controlled trials of adjuvant beta-blocker therapy versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease. Data was abstracted independently by two of the authors onto standardised forms and disagreements were resolved by discussion. Four randomised controlled trials were found comparing beta-blocker therapy with placebo in patients with idiopathic Parkinson's disease. These were double-blind cross-over studies involving a total of 72 patients. Three studies did not present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. The risk of a carry-over effect into the second arm meant that these results were not analysed. The fourth study presented data from each arm. This was in the form of a mean total score for tremor for each group. Details of the baseline scores, the numbers of patients in each group and standard deviations were not provided, meaning that the magnitude and significance of any changes due to therapy could not be calculated. One study reported a substantial fall in heart rate in 14 of the 22 patients, with one patient withdrawing after his heart rate dropped to 56 beats per minute (baseline heart rate was not reported). In view of this lack of evidence, it is impossible to determine whether beta-blocker therapy is effective and safe for the treatment of tremor in Parkinson's disease. The high frequency of bradycardia in one trial raises some concerns about the prescription of beta-blockers to normotensive elderly patients but the study was too small for the true degree of risk to be calculated.

Mirror therapy for improving motor function after stroke.

PubMed

Thieme, Holm; Mehrholz, Jan; Pohl, Marcus; Behrens, Johann; Dohle, Christian

2012-03-14

Mirror therapy is used to improve motor function after stroke. During mirror therapy, a mirror is placed in the patient's midsagittal plane, thus reflecting movements of the non-paretic side as if it were the affected side. To summarise the effectiveness of mirror therapy for improving motor function, activities of daily living, pain and visuospatial neglect in patients after stroke. We searched the Cochrane Stroke Group's Trials Register (June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to June 2011), EMBASE (1980 to June 2011), CINAHL (1982 to June 2011), AMED (1985 to June 2011), PsycINFO (1806 to June 2011) and PEDro (June 2011). We also handsearched relevant conference proceedings, trials and research registers, checked reference lists and contacted trialists, researchers and experts in our field of study. We included randomised controlled trials (RCTs) and randomised cross-over trials comparing mirror therapy with any control intervention for patients after stroke. Two review authors independently selected trials based on the inclusion criteria, documented the methodological quality of studies and extracted data. We analysed the results as standardised mean differences (SMDs) for continuous variables. We included 14 studies with a total of 567 participants that compared mirror therapy with other interventions. When compared with all other interventions, mirror therapy may have a significant effect on motor function (post-intervention data: SMD 0.61; 95% confidence interval (CI) 0.22 to 1.0; P = 0.002; change scores: SMD 1.04; 95% CI 0.57 to 1.51; P < 0.0001). However, effects on motor function are influenced by the type of control intervention. Additionally, mirror therapy may improve activities of daily living (SMD 0.33; 95% CI 0.05 to 0.60; P = 0.02). We found a significant positive effect on pain (SMD -1.10; 95% CI -2.10 to -0.09; P = 0.03) which is influenced by patient population. We found limited evidence for improving visuospatial neglect (SMD 1.22; 95% CI 0.24 to 2.19; P = 0.01). The effects on motor function were stable at follow-up assessment after six months. The results indicate evidence for the effectiveness of mirror therapy for improving upper extremity motor function, activities of daily living and pain, at least as an adjunct to normal rehabilitation for patients after stroke. Limitations are due to small sample sizes of most included studies, control interventions that are not used routinely in stroke rehabilitation and some methodological limitations of the studies.

Defect-driven localization crossovers in MBE-grown La-doped SrSn O3 films

NASA Astrophysics Data System (ADS)

Wang, Tianqi; Thoutam, Laxman Raju; Prakash, Abhinav; Nunn, William; Haugstad, Greg; Jalan, Bharat

2017-11-01

Through systematic control of cation stoichiometry using a hybrid molecular beam epitaxy method, we show a crossover from weak to strong localization of electronic carriers in La-doped SrSn O3 films on LaAl O3 (001). We demonstrate that substrate-induced dislocations in these films can have a strong influence on the electron phase coherence length resulting in two-dimensional to three-dimensional weak localization crossover. We discuss the correlation between electronic transport, and defects associated with nonstoichiometry and dislocations.

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

Exchangeability in the case-crossover design

PubMed Central

Mittleman, Murray A; Mostofsky, Elizabeth

2014-01-01

In cohort and case-control studies, confounding that arises as a result of differences in the distribution of determinants of the outcome between exposure groups leading to non-exchangeability are addressed by restriction, matching or with statistical models. In case-only studies, this issue is addressed by comparing each individual with his/herself. Although case-only designs use self-matching and only include individuals who develop the outcome of interest, issues of non-exchangeability are identical to those that arise in traditional case-control and cohort studies. In this review, we describe one type of case-only design, the case-crossover design, and discuss how the concept of exchangeability can be used to understand issues of confounding, carryover effects, period effects and selection bias in case-crossover studies. PMID:24756878

Systematic review with meta-analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea.

PubMed

Szajewska, H; Kołodziej, M

2015-10-01

Antibiotic-associated diarrhoea is a common complication of antibiotic use, but it can be prevented with administration of probiotics. To update our 2005 meta-analysis on the effectiveness of Saccharomyces boulardii in preventing antibiotic-associated diarrhoea in children and adults. The Cochrane Library, MEDLINE, and EMBASE databases were searched up until May 2015, with no language restrictions, for randomised controlled trials; additional references were obtained from reviewed articles. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Twenty-one randomised controlled trials (4780 participants), among which 16 were new trials, met the inclusion criteria for this updated systematic review. Administration of S. boulardii compared with placebo or no treatment reduced the risk of antibiotic-associated diarrhoea (as defined by the study investigators) in patients treated with antibiotics from 18.7% to 8.5% (risk ratio, RR: 0.47; 95% CI: 0.38-0.57, number needed to treat, NNT: 10; 95% CI: 9-13). In children, S. boulardii reduced the risk from 20.9% to 8.8% (6 randomised controlled trials, n=1653, RR: 0.43, 95% CI: 0.3-0.6); in adults, from 17.4% to 8.2% (15 randomised controlled trials, n=3114, RR: 0.49, 95% CI: 0.38-0.63). Moreover, S. boulardii reduced the risk of Clostridium difficile-associated diarrhoea; however, this reduction was significant only in children (2 randomised controlled trials, n = 579, RR: 0.25; 95% CI: 0.08-0.73) and not in adults (9 randomised controlled trials, n = 1441, RR: 0.8, 95% CI: 0.47-1.34). This meta-analysis confirms that S. boulardii is effective in reducing the risk of antibiotic-associated diarrhoea in children and adults. © 2015 John Wiley & Sons Ltd.

Study protocol of a multicentre randomised controlled trial of self-help cognitive behaviour therapy for working women with menopausal symptoms (MENOS@Work).

PubMed

Hunter, Myra S; Hardy, Claire; Norton, Sam; Griffiths, Amanda

2016-10-01

Hot flushes and night sweats (HFNS) - the main symptoms of the menopause transition - can reduce quality of life and are particularly difficult to manage at work. A cognitive behaviour therapy (CBT) intervention has been developed specifically for HFNS that is theoretically based and shown to reduce significantly the impact of HFNS in several randomised controlled trials (RCTs). Self-help CBT has been found to be as effective as group CBT for these symptoms, but these interventions are not widely available in the workplace. This paper describes the protocol of an RCT aiming to assess the efficacy of CBT for menopausal symptoms implemented in the workplace, with a nested qualitative study to examine acceptability and feasibility. One hundred menopausal working women, aged 45-60 years, experiencing bothersome HFNS for two months will be recruited from several (2-10) large organisations into a multicentre randomised controlled trial. Women will be randomly assigned to either treatment (a self-help CBT intervention lasting 4 weeks) or to a no treatment-wait control condition (NTWC), following a screening interview, consent, and completion of a baseline questionnaire. All participants will complete follow-up questionnaires at 6 weeks and 20 weeks post-randomisation. The primary outcome is the rating of HFNS; secondary measures include HFNS frequency, mood, quality of life, attitudes to menopause, HFNS beliefs and behaviours, work absence and presenteeism, job satisfaction, job stress, job performance, disclosure to managers and turnover intention. Adherence, acceptability and feasibility will be assessed at 20 weeks post-randomisation in questionnaires and qualitative interviews. Upon trial completion, the control group will also be offered the intervention. This is the first randomised controlled trial of a self-management intervention tailored for working women who have troublesome menopausal symptoms. Clin.Gov NCT02623374. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data.

PubMed

Tvete, Ingunn F; Olsen, Inge C; Fagerland, Morten W; Meland, Nils; Aldrin, Magne; Smerud, Knut T; Holden, Lars

2012-04-01

In active run-in trials, where patients may be excluded after a run-in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate. We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis. Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available. We assume equality of the various carry-over effects over time. The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes.

Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial.

PubMed

Franke, Andreas G; Gränsmark, Patrik; Agricola, Alexandra; Schühle, Kai; Rommel, Thilo; Sebastian, Alexandra; Balló, Harald E; Gorbulev, Stanislav; Gerdes, Christer; Frank, Björn; Ruckes, Christian; Tüscher, Oliver; Lieb, Klaus

2017-03-01

Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess - a competitive mind game requiring highly complex cognitive skills - can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200mg modafinil, 2×20mg methylphenidate, and 2×200mg caffeine or placebo in a 4×4 crossover design. They played twenty 15-minute games during two sessions against a chess program (Fritz 12; adapted to players' strength) and completed several neuropsychological tests. Marked substance effects were observed since all three substances significantly increased average reflection time per game compared to placebo resulting in a significantly increased number of games lost on time with all three treatments. Treatment effects on chess performance were not seen if all games (n=3059) were analysed. Only when controlling for game duration as well as when excluding those games lost on time, both modafinil and methylphenidate enhanced chess performance as demonstrated by significantly higher scores in the remaining 2876 games compared to placebo. In conjunction with results from neuropsychological testing we conclude that modifying effects of stimulants on complex cognitive tasks may in particular result from more reflective decision making processes. When not under time pressure, such effects may result in enhanced performance. Yet, under time constraints more reflective decision making may not improve or even have detrimental effects on complex task performance. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults.

PubMed

West, Sheila G; McIntyre, Molly D; Piotrowski, Matthew J; Poupin, Nathalie; Miller, Debra L; Preston, Amy G; Wagner, Paul; Groves, Lisa F; Skulas-Ray, Ann C

2014-02-01

The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6% (+2 mm) and basal blood flow volume by 22%. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.

A single serving of caffeinated coffee impairs postprandial glucose metabolism in overweight men.

PubMed

Robertson, Tracey M; Clifford, Michael N; Penson, Simon; Chope, Gemma; Robertson, M Denise

2015-10-28

Previous studies regarding the acute effects of coffee on glycaemic control have used a single large dose of coffee, typically containing the caffeine equivalent of 2-4 servings of coffee. This study investigates whether the acute effects of coffee are dose-dependent, starting with a single serving. A total of ten healthy overweight males participated in a two-part randomised double-blind cross-over study. In the first part, they ingested 2, 4 or 8 g instant decaffeinated coffee (DC) dissolved in 400 ml water with caffeine added in proportion to the DC (total 100, 200 or 400 mg caffeine) or control (400 ml water) all with 50 g glucose. In the second part, they ingested the same amounts of DC (2, 4, 8 g) or control, but with a standard 100 mg caffeine added to each. Capillary blood samples were taken every 15 min for 2 h after each drink and glucose and insulin levels were measured. Repeated measures ANOVA on glucose results found an effect when caffeine was varied in line with DC (P=0·008). Post hoc analysis revealed that both 2 and 4 g DC with varied caffeine content increased the glycaemic response v. There was no effect of escalating doses of DC when caffeine remained constant at 100 mg. These results demonstrate that one standard serving of coffee (2 g) is sufficient to affect glucose metabolism. Furthermore, the amount of caffeine found in one serving (100 mg) is sufficient to mask any potential beneficial effects of increasing other components. No dose-dependent effect was found.

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

PubMed

McInnes, Rhona J; Hillan, Edith; Clark, Diana; Gilmour, Harper

2004-10-01

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. Randomised controlled trial. The South Glasgow University Hospitals NHS Trust. Primigravidae and multigravidae in labour at term (37-42 weeks). Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. Analgesia requirements during labour and women's satisfaction with the method of pain relief. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Theory of planned behaviour variables and objective walking behaviour do not show seasonal variation in a randomised controlled trial.

PubMed

Williams, Stefanie L; French, David P

2014-02-05

Longitudinal studies have shown that objectively measured walking behaviour is subject to seasonal variation, with people walking more in summer compared to winter. Seasonality therefore may have the potential to bias the results of randomised controlled trials if there are not adequate statistical or design controls. Despite this there are no studies that assess the impact of seasonality on walking behaviour in a randomised controlled trial, to quantify the extent of such bias. Further there have been no studies assessing how season impacts on the psychological predictors of walking behaviour to date. The aim of the present study was to assess seasonal differences in a) objective walking behaviour and b) Theory of Planned Behaviour (TPB) variables during a randomised controlled trial of an intervention to promote walking. 315 patients were recruited to a two-arm cluster randomised controlled trial of an intervention to promote walking in primary care. A series of repeated measures ANCOVAs were conducted to examine the effect of season on pedometer measures of walking behaviour and TPB measures, assessed immediately post-intervention and six months later. Hierarchical regression analyses were conducted to assess whether season moderated the prediction of intention and behaviour by TPB measures. There were no significant differences in time spent walking in spring/summer compared to autumn/winter. There was no significant seasonal variation in most TPB variables, although the belief that there will be good weather was significantly higher in spring/summer (F = 19.46, p < .001). Season did not significantly predict intention or objective walking behaviour, or moderate the effects of TPB variables on intention or behaviour. Seasonality does not influence objectively measured walking behaviour or psychological variables during a randomised controlled trial. Consequently physical activity behaviour outcomes in trials will not be biased by the season in which they are measured. Previous studies may have overestimated the extent of seasonality effects by selecting the most extreme summer and winter months to assess PA. In addition, participants recruited to behaviour change interventions might have higher levels of motivation to change and are less affected by seasonal barriers. Current Controlled Trials ISRCTN95932902.

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Ju, Woong; Oh, Seung-Won; Park, Sang Min; Koo, Bon-Kwon; Park, Byung-Joo

2013-01-01

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. Design Meta-analysis of randomised controlled trials. Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria. Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry. Conclusion There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases. PMID:23335472

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

PubMed Central

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

2015-01-01

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

Washout policies in long-term indwelling urinary catheterisation in adults.

PubMed

Shepherd, Ashley J; Mackay, William G; Hagen, Suzanne

2017-03-06

People requiring long-term bladder draining with an indwelling catheter can experience catheter blockage. Regimens involving different solutions can be used to wash out catheters with the aim of preventing blockage. This is an update of a review published in 2010. To determine if certain washout regimens are better than others in terms of effectiveness, acceptability, complications, quality of life and critically appraise and summarise economic evidence for the management of long-term indwelling urinary catheterisation in adults. We searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings to 23 May 2016. We also examined all reference lists of identified trials and contacted manufacturers and researchers in the field. All randomised and quasi-randomised trials comparing catheter washout policies (e.g. washout versus no washout, different washout solutions, frequency, duration, volume, concentration, method of administration) in adults (aged 16 years and above) in any setting (i.e. hospital, nursing/residential home, community) with an indwelling urethral or suprapubic catheter for more than 28 days. Two review authors independently extracted data. Disagreements were resolved by discussion. Data were assessed and analysed as described in the Cochrane Handbook. If data in trials were not fully reported, clarification was sought from the study authors. For categorical outcomes, the numbers reporting an outcome were related to the numbers at risk in each group to derive a risk ratio (RR). For continuous outcomes, means and standard deviations were used to derive mean differences (MD). We included seven trials involving a total of 349 participants, 217 of whom completed the studies. Three were cross-over and four were parallel-group randomised controlled trials (RCTs). Of these, two trials were added for this update (one parallel-group RCT with 40 participants and one cross-over RCT with 67 participants). Analyses of three cross-over trials yielded suboptimal results because they were based on between-group differences rather than individual participants' differences for sequential interventions. Two parallel-group trials had limited clinical value: one combined results for suprapubic and urethral catheters and the other provided data for only four participants. Only one trial was free of significant methodological limitations, but there were difficulties with recruitment and maintaining participants in this study.The included studies reported data on six of the nine primary and secondary outcome measures. None of the trials addressed: number of catheters used, washout acceptability measures (including patient satisfaction, patient discomfort, pain and ease of use), or health status/measures of psychological health; very limited data were collected for health economic outcomes. Trials assessed only three of the eight intervention comparisons identified. Two trials reported in more than one comparison group.Four trials compared washout (either saline or acidic solution) with no washout. We are uncertain if washout solutions (saline or acidic), compared to no washout solutions, has an important effect on the rate of symptomatic urinary tract infection or length of time each catheter was in situ because the results are imprecise.Four trials compared different types of washout solution; saline versus acidic solutions (2 trials); saline versus acidic solution versus antibiotic solution (1 trial); saline versus antimicrobial solution (1 trial). We are uncertain if type of washout solution has an important effect on the rate of symptomatic urinary tract infection or length of time each catheter was in situ because the results are imprecise.One trial compared different compositions of acidic solution (stronger versus weaker solution). We are uncertain if different compositions of acidic solutions has an important effect on the rate of symptomatic urinary tract infection or length of time each catheter was in situ because only 14 participants (of 25 who were recruited) completed this 12 week, three arm trial.Four studies reported on possible harmful effects of washout use, such as blood in the washout solution, changes in blood pressure and bladder spasms.There were very few small trials that met the review inclusion criteria. The high risk of bias of the included studies resulted in the evidence being graded as low or very low quality. Data from seven trials that compared different washout policies were limited, and generally, of poor methodological quality or were poorly reported. The evidence was not adequate to conclude if washouts were beneficial or harmful. Further rigorous, high quality trials that are adequately powered to detect benefits from washout being performed as opposed to no washout are needed. Trials comparing different washout solutions, washout volumes, and frequencies or timings are also needed.

Ghrelin for the management of cachexia associated with cancer.

PubMed

Khatib, Mahalaqua Nazli; Shankar, Anuraj H; Kirubakaran, Richard; Gaidhane, Abhay; Gaidhane, Shilpa; Simkhada, Padam; Quazi Syed, Zahiruddin

2018-02-28

Cancer sufferers are amongst the most malnourished of all the patient groups. Studies have shown that ghrelin, a gut hormone can be a potential therapeutic agent for cachexia (wasting syndrome) associated with cancer. A variety of mechanisms of action of ghrelin in people with cancer cachexia have been proposed. However, safety and efficacy of ghrelin for cancer-associated cachexia have not been systematically reviewed. The aim of this review was to assess whether ghrelin is associated with better food intake, body composition and survival than other options for adults with cancer cachexia. To assess the efficacy and safety of ghrelin in improving food intake, body composition and survival in people with cachexia associated with cancer. We searched CENTRAL, MEDLINE and Embase without language restrictions up to July 2017. We also searched for ongoing studies in trials registers, performed handsearching, checked bibliographic references of relevant articles and contacted authors and experts in the field to seek potentially relevant research. We applied no restrictions on language, date, or publication status. We included randomised controlled (parallel-group or cross-over) trials comparing ghrelin (any formulation or route of administration) with placebo or an active comparator in adults (aged 18 years and over) who met any of the international criteria for cancer cachexia. Two review authors independently assessed studies for eligibility. Two review authors then extracted data and assessed the risk of bias for individual studies using standard Cochrane methodology. For dichotomous variables, we planned to calculate risk ratio with 95% confidence intervals (CI) and for continuous data, we planned to calculate mean differences (MD) with 95% CI. We assessed the evidence using GRADE and created 'Summary of findings' tables. We screened 926 individual references and identified three studies that satisfied the inclusion criteria. Fifty-nine participants (37 men and 22 women) aged between 54 and 78 years were randomised initially, 47 participants completed the treatment. One study had a parallel design and two had a cross-over design. The studies included people with a variety of cancers and also differed in the dosage, route of administration, frequency and duration of treatment.One trial, which compared ghrelin with placebo, found that ghrelin improved food intake (very low-quality evidence) and had no adverse events (very low-quality evidence). Due to unavailability of data we were unable to report on comparisons for ghrelin versus no treatment or alternative experimental treatment modalities, or ghrelin in combination with other treatments or ghrelin analogues/ghrelin mimetics/ghrelin potentiators. Two studies compared a higher dose of ghrelin with a lower dose of ghrelin, however due to differences in study designs and great diversity in the treatment provided we did not pool the results. In both trials, food intake did not differ between participants on higher-dose and lower-dose ghrelin. None of the included studies assessed data on body weight. One study reported higher adverse events with a higher dose as compared to a lower dose of ghrelin.All studies were at high risk of attrition bias and bias for size of the study. Risk of bias in other domains was unclear or low.We rated the overall quality of the evidence for primary outcomes (food intake, body weight, adverse events) as very low. We downgraded the quality of the evidence due to lack of data, high or unclear risk of bias of the studies and small study size. There is insufficient evidence to be able to support or refute the use of ghrelin in people with cancer cachexia. Adequately powered randomised controlled trials focusing on evaluation of safety and efficacy of ghrelin in people with cancer cachexia is warranted.

Comparison of injection pain caused by the DentalVibe Injection System versus a traditional syringe for inferior alveolar nerve block anaesthesia in paediatric patients.

PubMed

Elbay, M; Şermet Elbay, Ü; Yıldırım, S; Uğurluel, C; Kaya, C; Baydemir, C

2015-06-01

To compare paediatric patients' pain during needle insertion and injection in inferior alveoler nerve block (IANB) anaesthesia injected by either a traditional syringe (TS) or the DentalVibe Injection Comfort System (DV). the study was a randomised controlled crossover clinical trial, comprised of 60 children aged 6-12 requiring an operative procedure with IANB anaesthesia on their mandibular molars bilaterally. One of the molar teeth was treated with TS and the contralateral tooth was treated with DV. On each visit, subjective and objective pain was evaluated using the Wond-Baker Faces Pain Rating Scale (PRS) and the Face, Legg, Cry, Consolability Scale (FLACC Scale). Patients were asked which anaesthesia technique they preferred. Data were analysed using Wilcoxon signed rank, Spearman correlation, and Mann-Whitney U tests. There were no statistically significant differences for pain evalution during needle insertion and injection of each injection system. However, a negative correlation was found on the FLACC between age and pain scores during injection after using DV. Paediatric patients experienced similar pain during IANB anaesthesia administered with TS and DV. With increased age, pain values reduced during anaesthetic agent injection with DV according to FLACC. The traditional procedure was preferred to DV in paediatric patients.

Effects of dietary caffeine on EEG, performance and mood when rested and sleep restricted.

PubMed

Keane, Michael A; James, Jack E

2008-12-01

Until recently, little account had been taken of the confounding effects of caffeine withdrawal and withdrawal reversal when examining the net effects of dietary caffeine. By including a manipulation involving sleep restriction, the present study aimed to extend recent findings from research in which caffeine withdrawal and withdrawal reversal were controlled. The main aims of the study were to examine the net effects of caffeine, as well as its potential restorative effects following sleep restriction, on EEG, performance and mood. A randomised cross-over design was used in which 15 participants alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for four consecutive weeks following either usual sleep or sleep restriction. EEG activity was measured at 32 sites during eyes closed, eyes open and performance of a vigilance task. Modest effects of caffeine were found in the delta and beta bandwidths, but no main effects of caffeine were observed in the theta or alpha bandwidths. Overall, the effects of caffeine on EEG activity were relatively few, weak and inconsistent, and no evidence was found of net restorative effects of caffeine for any outcome variables. The findings do not support the use of caffeine as a means for enhancing human function or as an antidote to the negative effects of sleep loss.

Oral antioxidant therapy for marginal dry eye.

PubMed

Blades, K J; Patel, S; Aidoo, K E

2001-07-01

To assess the efficacy of an orally administered antioxidant dietary supplement for managing marginal dry eye. A prospective, randomised, placebo controlled trial with cross-over. Eye Clinic, Department of Vision Sciences, Glasgow Caledonian University. Forty marginal dry eye sufferers composed of 30 females and 10 males (median age 53 y; range 38-69 y). Baseline assessments were made of tear volume sufficiency (thread test), tear quality (stability), ocular surface status (conjunctival impression cytology) and dry eye symptoms (questionnaire). Each subject was administered courses of active treatment, placebo and no treatment, in random order for 1 month each and results compared to baseline. Tear stability and ocular surface status were significantly improved following active treatment (P<0.05). No changes from baseline were detected following administration of placebo and no treatment (P>0.05). Absolute increase in tear stability correlated with absolute change in goblet cell population density. Tear volume was not improved following any treatment period and dry eye symptom responses were subject to placebo effect. Oral antioxidants improved both tear stability and conjunctival health, although it is not yet understood whether increased ocular surface health mediates increased tear stability or vice versa. This study was supported by a PhD scholarship funded by the Department of Vision Sciences, Glasgow Caledonian University, Scotland. Antioxidant supplements and placebos were kindly donated by Vitabiotics.

Effect of Tea Theaflavins and Catechins on Microvascular Function

PubMed Central

Fuchs, Dagmar; de Graaf, Young; van Kerckhoven, Roeland; Draijer, Richard

2014-01-01

Beneficial effects of flavonoid-rich black and green tea on macrocirculation have been well established. Theaflavins are unique to black tea as they are formed from catechins during the enzymatic oxidation of tea leaves. The study was performed to gain more insight into the effects of theaflavins on microcirculation and to compare effects with another important flavonoid class, the green tea derived catechins, which have been reported to improve vascular function. Twenty-four healthy subjects were included in a double-blind, placebo-controlled, randomised, cross-over study. On six different days, subjects received capsules with a single dose of catechins (500 mg), four varying doses of theaflavins (100 to 500 mg) or placebo. Microcirculation was assessed after each treatment by Pulse Amplitude Tonometry (EndoPAT) at baseline and 2, 4 and 6 h after test product intake. The EndoPAT reactive hyperemia response was improved by 500 mg catechins (reactive hyperemia index (RHI): 0.2; p = 0.04) and by 500 mg theaflavins (RHI: 0.19; p = 0.06) compared to placebo. Also, 300 mg theaflavins increased the RHI (0.28; p = 0.02), but no effects were observed at lower doses. The study suggests moderate effects of single doses of catechins and theaflavins on peripheral microcirculation. PMID:25514559

Effects of the Red Bull energy drink on cognitive function and mood in healthy young volunteers.

PubMed

Wesnes, Keith A; Brooker, Helen; Watson, Anthony W; Bal, Wendy; Okello, Edward

2017-02-01

The present study compared the cognitive and mood effects of two commercially available products, Red Bull energy drink 250 mL and Red Bull Sugarfree energy drink 250 mL, together with a matching placebo 250 mL. Twenty-four healthy young volunteers took part in a randomised, placebo controlled, double-blind, three-way cross-over study. Cognitive function was assessed using an integrated set of nine computerised tests of attention, working and episodic memory. On each study day the volunteers received a standardised breakfast prior to completing a baseline performance on cognitive tests and mood scales, followed by the consumption of the study drink. The cognitive tests and scales were then re-administered at 30, 60 and 90 min post-dose. Red Bull was found to produce significant improvements over both the Sugarfree version and the placebo drink on two composite scores from the six working and episodic memory tests; one combining the 12 accuracy measures from the six tasks and the other the average speed of correct responses from the working memory and episodic recognition memory tasks. These improvements were in the range of a medium effect size, which reflects a substantial enhancement to memory in young volunteers.

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia.

PubMed

Duprat, Romain; Wu, Guo-Rong; De Raedt, Rudi; Baeken, Chris

2017-08-09

Accelerated intermittent theta-burst stimulation (aiTBS) anti-depressive working mechanisms are still unclear. Because aiTBS may work through modulating the reward system and the level of anhedonia may influence this modulation, we investigated the effect of aiTBS on reward responsiveness in high and low anhedonic MDD patients. In this registered RCT (NCT01832805), 50 MDD patients were randomised to a sham-controlled cross-over aiTBS treatment protocol over the left dorsolateral prefrontal cortex (DLPFC). Patients performed a probabilistic learning task in fMRI before and after each week of stimulation. Task performance analyses did not show any significant effects of aiTBS on reward responsiveness, nor differences between both groups of MDD patients. However, at baseline, low anhedonic patients displayed higher neural activity in the caudate and putamen. After the first week of aiTBS treatment, in low anhedonic patients we found a decreased neural activity within the reward system, in contrast to an increased activity observed in high anhedonic patients. No changes were observed in reward related neural regions after the first week of sham stimulation. Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.

Effects of blue light and caffeine on mood.

PubMed

Ekström, Johan G; Beaven, C Martyn

2014-09-01

Both short wavelength (blue) light and caffeine have been studied for their mood enhancing effects on humans. The ability of blue light to increase alertness, mood and cognitive function via non-image forming neuropathways has been suggested as a non-pharmacological countermeasure for depression across a range of occupational settings. This experimental study compared blue light and caffeine and aimed to test the effects of blue light/placebo (BLU), white light/240-mg caffeine (CAF), blue light/240-mg caffeine (BCAF) and white light/placebo (PLA), on mood. A randomised, controlled, crossover design study was used, in a convenience population of 20 healthy volunteers. The participants rated their mood on the Swedish Core Affect Scales (SCAS) prior to and after each experimental condition to assess the dimensions of valence and activation. There was a significant main effect of light (p = 0.009), and the combination of blue light and caffeine had clear positive effects on core effects (ES, ranging from 0.41 to 1.20) and global mood (ES, 0.61 ± 0.53). The benefits of the combination of blue light and caffeine should be further investigated across a range of applications due to the observed effects on the dimensions of arousal, valence and pleasant activation.

Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers.

PubMed

Dumont, G J H; Wezenberg, E; Valkenberg, M M G J; de Jong, C A J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

2008-04-01

In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function.

Effect of Lactobacillus sporogenes on oral isoflavones bioavailability: single dose pharmacokinetic study in menopausal women.

PubMed

Benvenuti, Claudio; Setnikar, Ivo

2011-01-01

To verify the single dose bioavailability of two oral formulations of soy isoflavones, with and without lactobacilli, in menopausal women in antibiotic therapy. Twelve menopause women (mean age 54.3 years, BMI 25.0 kg/m2) participated in a controlled cross-over study. Reference and test treatments were: R = tablets containing soy isoflavones 60 mg (genistin 30 mg + daidzin 30 mg) + calcium and vitamin D3; E = R + 500 million vital spores of Lactobacillus sporogenes (E is Estromineral, a food supplement containing soy isoflavones 60 mg, calcium 141 mg and vitamin D3 5 microg). The design included 2 periods of 5 days of amoxicillin + clavulanate treatment with a 2-week wash-out. After each period alternatively a single dose of each formulation was given in randomised sequence. Genistein and daidzein were determined in plasma by HPLC, sampled 10 times within 24 h after dosing. Genistein pharmacokinetics parameters were higher after E than after R administration: peak plasma concentration (Cmax) +24.3%, area under the concentration curve (AUC0-24) +24.4% and mean residence time +11.0%. Daidzein Cmax and AUC showed a larger variability on R, evidenced by higher scatter from the mean on the formulation without lactobacilli. A trend is shown for a greater absorption of genistein from a formulation containing lactobacilli.

Food intake and appetite following school-based high-intensity interval training in 9-11-year-old children.

PubMed

Morris, Anna; Cramb, Robert; Dodd-Reynolds, Caroline J

2018-02-01

Using a randomised cross-over design, free-living lunch intake and subjective appetite were examined in 10 children (9.8 ± 0.6 years) following high-intensity interval training (HIIT) versus a control sedentary (SED) period, within a school setting. The 22-min HIIT took place during a regular PE lesson and consisted of two rounds of 4 × 30 s sprints. Foods were offered at a regular school lunch immediately following HIIT and SED and were matched between conditions. All food was covertly weighed before and after the meal. Hunger, fullness and prospective consumption were reported immediately before and after HIIT/SED, using visual analogue scales. Heart rate was higher during HIIT than SED (159.3 ± 23.1 vs. 76.9 ± 2.2 bpm, P < 0.05). Lunch energy intake was not different (P = 0.52) following HIIT, compared to SED (2.06 ± 0.35 vs. 2.09 ± 0.29 MJ, respectively). There were no significant differences in macronutrient intake or subjective appetite (P > 0.05). Results suggest that HIIT can be implemented in a PE lesson immediately before lunch, without causing a compensatory increase in food consumption.

A pilot study using synthetic feline facial pheromone for the management of feline idiopathic cystitis.

PubMed

Gunn-Moore, D A; Cameron, M E

2004-06-01

Synthetic feline facial pheromone (FFP) (Feliway; Ceva Animal Health) was assessed for the management of cats with recurrent feline idiopathic cystitis (FIC). Nine of 12 cats completed the randomised, double-blinded, placebo-controlled, crossover pilot study. They had their environment treated daily with either FFP or placebo for 2 months, after which time the treatment groups were reversed. Owners used visual analogue scales to define the severity of their cat's clinical signs and behavioural changes. Five (56%) of the owners stated that their cat's overall health was better when they were using FFP. Four (44%) of the owners noticed no difference between when using the FFP and when using the placebo. While there were no statistical differences between the two treatment groups there was a trend for the cats exposed to FFP to show fewer days with clinical signs of cystitis (FFP total, mean per cat+/-standard deviation, 30, 4.3+/-6.7; placebo 69, 9.9+/-19.1), a lower overall clinical score (1667, 238+/-476; 2009, 287+/-425), a reduced number of episodes of cystitis (9, 1.3+/-2.0; 10, 1.4+/-2.1) and reduced negative behavioural traits (e.g., less aggression and fear) (-128, -18.3+/-65.8; -73, -10.4+/-35.1).

No influence of supplemental dietary calcium intake on the bioavailability of spinach carotenoids in humans.

PubMed

Corte-Real, Joana; Guignard, Cédric; Gantenbein, Manon; Weber, Bernard; Burgard, Kim; Hoffmann, Lucien; Richling, Elke; Bohn, Torsten

2017-06-01

Dietary carotenoid intake, especially from fruits and vegetables, has been associated with a reduced incidence of several chronic diseases. However, its bioavailability can vary, depending on the food matrix and host factors. Recently, it has been suggested that divalent minerals negatively impinge on carotenoid bioavailability by reducing bile-salt and non-esterified fatty-acid levels in the gut, which normally aid in emulsifying carotenoids. The aim of the present study was to investigate whether supplemental Ca would negatively influence carotenoid absorption in humans. A total of twenty-five healthy, non-obese men (age: 20-46 years, BMI<30 kg/m2) were recruited for this postprandial, randomised, crossover, double-blinded trial. Following a randomised block design, each participant received (after 2-week washout periods), on three occasions separated by 1 week, 270 g of spinach-based meals (8·61 (sd 1·08) mg carotenoids/100 g fresh weight), supplemented with 0, 500 or 1000 mg of Ca (as calcium carbonate), with each participant acting as his or her own control. Blood samples were collected at regular postprandial intervals for up to 10 h following test meal intake, and standardised lunches were served. TAG-rich lipoprotein fractions were separated and carotenoid concentrations determined. AUC for meals without supplemented Ca were 22·72 (sem 2·78) nmol×h/l (lutein), 0·19 (sem 3·90) nmol×h/l (β-carotene) and 2·80 (sem 1·75) nmol×h/l (β-cryptoxanthin). No significant influence of supplementation with either 500 or 1000 mg of supplemental Ca was found. In conclusion, Ca - the most abundant divalent mineral in the diet - given at high but physiological concentrations, does not appear to have repercussions on the bioavailability of carotenoids from a spinach-based meal.

A randomised crossover study to compare the cross-sectional and longitudinal approaches to ultrasound-guided peripheral venepuncture in a model.

PubMed

Griffiths, James; Carnegie, Amadeus; Kendall, Richard; Madan, Rajeev

2017-12-01

Ultrasound-guided peripheral intravenous access may present an alternative to central or intraosseous access in patients with difficult peripheral veins. Using venepuncture of a phantom model as a proxy, we investigated whether novice ultrasound users should adopt a cross-sectional or longitudinal approach when learning to access peripheral veins under ultrasound guidance. This result would inform the development of a structured training method for this procedure. We conducted a randomised controlled trial of 30 medical students. Subjects received 35 min of training, then attempted to aspirate 1 ml of synthetic blood from a deep vein in a training model under ultrasound guidance. Subjects attempted both the cross-sectional and longitudinal approaches. Group 1 used cross-sectional first, followed by longitudinal. Group 2 used longitudinal first, then cross-sectional. We measured the time from first puncture of the model's skin to aspiration of fluid, and the number of attempts required. Subjects also reported difficulty ratings for each approach. Paired sample t-tests were used for statistical analysis. The mean number of attempts was 1.13 using the cross-sectional approach, compared with 1.30 using the longitudinal approach (p = 0.17). Mean time to aspiration of fluid was 45.1 s using the cross-sectional approach and 52.8 s using the longitudinal approach (p = 0.43). The mean difficulty score out of 10 was 3.97 for the cross-sectional approach and 3.93 for the longitudinal approach (p = 0.95). We found no significant difference in effectiveness between the cross-sectional and longitudinal approaches to ultrasound-guided venepuncture when performed on a model. We believe that both approaches should be included when teaching ultrasound-guided peripheral vascular access. To confirm which approach would be best in clinical practice, we advocate future testing of both approaches on patients.

Simulated presence therapy for dementia: a systematic review protocol.

PubMed

Abraha, Iosief; Rimland, Joseph M; Lozano-Montoya, Isabel; Dell'Aquila, Giuseppina; Vélez-Díaz-Pallarés, Manuel; Trotta, Fabiana M; Cherubini, Antonio

2016-05-11

The majority of patients with dementia develop behavioural and psychological symptoms of dementia (BPSD). Non-pharmacological interventions are an appealing alternative for the treatment of BPSD in patients with dementia. Simulated presence therapy (SPT) is a simple and inexpensive non-pharmacological intervention that can be used to treat BPSD. We propose a Cochrane protocol for the collection and assessment of evidence concerning the efficacy of SPT to treat relevant outcomes in people with dementia. We will search the following electronic databases: the Cochrane Dementia and Cognitive Improvement Group's Specialised Register MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, CENTRAL and a number of trial registers as well as grey literature sources. We will include randomised and quasi-randomised controlled trials (including cross-over studies) that evaluated SPT in people with dementia. Comparators such as usual care with no additional activity, or any activity that differs in content and approach from SPT, but is additional to usual care, will be considered. The primary outcomes of interest will comprise behavioural and psychological symptoms, as measured by relevant scales, and quality of life. Two review authors working independently and in tandem will be involved in title and abstract screening, full-text screening and data abstraction. Where possible, quantitative data will be pooled, and relative risk and mean difference with 95% CI will be employed for dichotomous and continuous data, respectively. Assessment of risk of bias will be performed using the Cochrane risk-of-bias tool and the Grades of Recommendation, Assessment, Development and Evaluation approach. Ethics approval is not required. The final results of this systematic review will be presented to the Cochrane Library and will also be disseminated at relevant conference presentations. CRD42015029778. 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/

Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

PubMed

Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J

2015-02-28

There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

Safety and feasibility evaluation of tourniquets for total knee replacement (SAFE-TKR): study protocol.

PubMed

Wall, Peter Dh; Ahmed, Imran; Metcalfe, Andrew; Price, Andrew J; Seers, Kate; Hutchinson, Charles E; Parsons, Helen; Warwick, Jane; Rahman, Bushra; Brown, Jaclyn; Underwood, Martin

2018-04-10

This study is designed to determine whether a full randomised controlled trial (RCT) examining the clinical effectiveness and safety of total knee replacement surgery with or without a tourniquet is warranted and feasible. Single centre, patient-blinded and assessor-blinded RCT. A computer-generated randomisation service will allocate 50 participants into one of two trial treatments, surgery with or without a tourniquet. The primary objective is to estimate recruitment, crossovers and follow-up of patients. All patients will have an MRI scan of their brain preoperatively and day 1 or 2 postoperatively to identify ischaemic cerebral emboli (primary clinical outcome). Oxford Cognitive Screen, Montreal Cognitive Assessment and Mini-Mental State Examination will be evaluated as outcome tools for measuring cognitive impairment at days 1, 2 and 7 postoperatively. Thigh pain, blood transfusion requirements, venous thromboembolism, revision surgery, surgical complications, mortality and Oxford knee and five-level EuroQol-5D scores will be collected over 12 months. Integrated qualitative research study : 30 trial patients and 20 knee surgeons will take part in semistructured interviews. Interviews will capture views regarding the pilot trial and explore barriers and potential solutions to a full trial. Multicentre cohort study : UK National Joint Registry data will be linked to Hospital Episode Statistics to estimate the relationship between tourniquet use and venous thromboembolic event, length of hospital stay, risk of revision surgery and death. The study will conclude with a multidisciplinary workshop to reach a consensus on whether a full trial is warranted and feasible. National Research Ethics Committee (West Midlands-Edgbaston) approved this study on 27 January 2016 (15/WM/0455). The study is sponsored by University of Warwick and University Hospitals Coventry and Warwickshire. The results will be disseminated via high-impact peer-reviewed publication. ISRCTN20873088; 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.

Auditory training changes temporal lobe connectivity in 'Wernicke's aphasia': a randomised trial.

PubMed

Woodhead, Zoe Vj; Crinion, Jennifer; Teki, Sundeep; Penny, Will; Price, Cathy J; Leff, Alexander P

2017-07-01

Aphasia is one of the most disabling sequelae after stroke, occurring in 25%-40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using 'Earobics' software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.Clinical trial registrationThis trial was registered with EudraCT (2005-004215-30, https:// eudract .ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/). © 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.

Genetic algorithm with maximum-minimum crossover (GA-MMC) applied in optimization of radiation pattern control of phased-array radars for rocket tracking systems.

PubMed

Silva, Leonardo W T; Barros, Vitor F; Silva, Sandro G

2014-08-18

In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence.

Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) Applied in Optimization of Radiation Pattern Control of Phased-Array Radars for Rocket Tracking Systems

PubMed Central

Silva, Leonardo W. T.; Barros, Vitor F.; Silva, Sandro G.

2014-01-01

In launching operations, Rocket Tracking Systems (RTS) process the trajectory data obtained by radar sensors. In order to improve functionality and maintenance, radars can be upgraded by replacing antennas with parabolic reflectors (PRs) with phased arrays (PAs). These arrays enable the electronic control of the radiation pattern by adjusting the signal supplied to each radiating element. However, in projects of phased array radars (PARs), the modeling of the problem is subject to various combinations of excitation signals producing a complex optimization problem. In this case, it is possible to calculate the problem solutions with optimization methods such as genetic algorithms (GAs). For this, the Genetic Algorithm with Maximum-Minimum Crossover (GA-MMC) method was developed to control the radiation pattern of PAs. The GA-MMC uses a reconfigurable algorithm with multiple objectives, differentiated coding and a new crossover genetic operator. This operator has a different approach from the conventional one, because it performs the crossover of the fittest individuals with the least fit individuals in order to enhance the genetic diversity. Thus, GA-MMC was successful in more than 90% of the tests for each application, increased the fitness of the final population by more than 20% and reduced the premature convergence. PMID:25196013

Review of Randomised Controlled Trials of Internet Interventions for Mental Disorders and Related Conditions

ERIC Educational Resources Information Center

Griffiths, Kathleen M.; Christensen, Helen

2006-01-01

Self-help Internet interventions have the potential to enable consumers to play a central role in managing their own health. This paper contains a systematic review of 15 randomised controlled trials of the effectiveness of self-help Internet interventions for mental disorders and related conditions. Conditions addressed by the interventions…

Representation of People with Intellectual Disabilities in Randomised Controlled Trials on Antipsychotic Treatment for Behavioural Problems

ERIC Educational Resources Information Center

Scheifes, A.; Stolker, J. J.; Egberts, A. C. G.; Nijman, H. L. I.; Heerdink, E. R.

2011-01-01

Background: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs.…

Effect of a Universal Anxiety Prevention Programme (FRIENDS) on Children's Academic Performance: Results from a Randomised Controlled Trial

ERIC Educational Resources Information Center

Skryabina, Elena; Taylor, Gordon; Stallard, Paul

2016-01-01

Background: Evaluations of school-based anxiety prevention programmes have reported improvements in psychological functioning although little is known about their effect upon educational outcomes. Methods: One thousand three hundred and sixty-two children from 40 primary schools in England took part in the randomised controlled trial, Preventing…

A Randomised Controlled Trial to Determine the Effectiveness of an Early Psychological Intervention with Children Involved in Road Traffic Accidents

ERIC Educational Resources Information Center

Stallard, Paul; Velleman, Richard; Salter, Emma; Howse, Imogen; Yule, William; Taylor, Gordon

2006-01-01

Objective: To determine whether an early intervention using a psychological debriefing format is effective in preventing psychological distress in child road traffic accident survivors. Design: Randomised controlled trial. Setting: Accident and Emergency Department, Royal United Hospital, Bath. Subjects: 158 children aged 7-18. Follow-up…

The Effectiveness of Picture Exchange Communication System (PECS) Training for Teachers of Children with Autism: A Pragmatic, Group Randomised Controlled Trial

ERIC Educational Resources Information Center

Howlin, Patricia; Gordon, R. Kate; Pasco, Greg; Wade, Angie; Charman, Tony

2007-01-01

Objective: To assess the effectiveness of expert training and consultancy for teachers of children with autism spectrum disorder in the use of the Picture Exchange Communication System (PECS). Method: Design: Group randomised, controlled trial (3 groups: immediate treatment, delayed treatment, no treatment). Participants: 84 elementary school…

"Every Child Counts": Testing Policy Effectiveness Using a Randomised Controlled Trial, Designed, Conducted and Reported to CONSORT Standards

ERIC Educational Resources Information Center

Torgerson, Carole; Wiggins, Andy; Torgerson, David; Ainsworth, Hannah; Hewitt, Catherine

2013-01-01

We report a randomised controlled trial evaluation of an intensive one-to-one numeracy programme--"Numbers Count"--which formed part of the previous government's numeracy policy intervention--"Every Child Counts." We rigorously designed and conducted the trial to CONSORT guidelines. We used a pragmatic waiting list design to…

Intelligence and Persisting with Medication for Two Years: Analysis in a Randomised Controlled Trial

ERIC Educational Resources Information Center

Deary, Ian J.; Gale, Catharine R.; Stewart, Marlene C. W.; Fowkes, F. Gerald R.; Murray, Gordon D.; Batty, G. David; Price, Jacqueline F.

2009-01-01

The study examined whether verbal intelligence is associated with persisting to take medication for up to two years. The design is a prospective follow-up of compliance with taking medication in high-risk individuals participating in a randomised, placebo-controlled trial set in Central Scotland. Participants were 1993 people aged between 50 and…

Stress in Fathers of Moderately and Late Preterm Infants: A Randomised Controlled Trial

ERIC Educational Resources Information Center

Ravn, Ingrid Helen; Lindemann, Rolf; Smeby, Nina Aarhus; Bunch, Eli Haugen; Sandvik, Leiv; Smith, Lars

2012-01-01

The atypical behaviour of preterm infants can elicit stress in fathers and influence their ability to perceive and interpret infants' cues. This study investigated whether fathers of moderately and late preterm infants were more stressed than fathers of term infants. In a randomised controlled trial, we also studied the effect of the Mother-Infant…

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

PubMed

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

2015-12-09

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

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

PubMed

Bayram, N; van Wely, M; Vandekerckhove, P; Lilford, R; van Der Veen, F

2000-01-01

In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis

PubMed Central

Schwartz, J

2004-01-01

Background: Numerous studies have reported that day-to-day changes in particulate air pollution are associated with day-to-day changes in deaths. Recently, several reports have indicated that the software used to control for season and weather in some of these studies had deficiencies. Aims: To investigate the use of the case-crossover design as an alternative. Methods: This approach compares the exposure of each case to their exposure on a nearby day, when they did not die. Hence it controls for seasonal patterns and for all slowly varying covariates (age, smoking, etc) by matching rather than complex modelling. A key feature is that temperature can also be controlled by matching. This approach was applied to a study of 14 US cities. Weather and day of the week were controlled for in the regression. Results: A 10 µg/m3 increase in PM10 was associated with a 0.36% increase in daily deaths from internal causes (95% CI 0.22% to 0.50%). Results were little changed if, instead of symmetrical sampling of control days the time stratified method was applied, when control days were matched on temperature, or when more lags of winter time temperatures were used. Similar results were found using a Poisson regression, but the case-crossover method has the advantage of simplicity in modelling, and of combining matched strata across multiple locations in a single stage analysis. Conclusions: Despite the considerable differences in analytical design, the previously reported associations of particles with mortality persisted in this study. The association appeared quite linear. Case-crossover designs represent an attractive method to control for season and weather by matching. PMID:15550600

Evaluation of 5 Hour Energy Drink on the Blood Pressure and Electrocardiograph Parameters on Young Healthy Volunteers: A Randomized, Double Blind, Crossover, Placebo-Controlled Trial

DTIC Science & Technology

2014-02-11

Travis AFB CA INSTITUTIONAL REVIEW BOARD (IRB) ()~\\) Non-Exempt Study Final Report p3YVJ (Please 1J!J!£ all information. Use additional pages if...QTc interval after acute and chronic consumption. METHODS: This was a randomized, placebo controlled, crossover study enrolling young healthy volunteers...not on any medications. Subjects received the study drink (5 Hour Energy shot or placebo) twice daily separated by approximately 7 hours for the

The effect of ankle brace type on braking response time-A randomised study.

PubMed

Dammerer, Dietmar; Waidmann, Cornelia; Haid, Christian; Thaler, Martin; Krismer, Martin; Liebensteiner, Michael C

2015-11-01

The question whether or not a patient with an ankle brace should drive a car is of obvious importance because brake response time (BRT) is considered one of the most important factors for driving safety. Applying a crossover study design, 70 healthy participants (35 women, 35 men) participated in our study. BRT was assessed using a custom-made driving simulator. We assessed BRT under six conditions: without a brace (control) (1), with a typical postoperative ankle brace with adjustable ROM and the settings: unrestricted (2), fixed at 15° (3) plantar flexion, restricted with 15°/50° (4) (dorsal/plantar flexion), a brace for ligament instabilities (5) and an elastic ankle bandage (6). Participants were instructed to apply the brake pedal exclusively with the right foot as quickly as possible on receipt of a visual stimulus. The 70 participants showed significantly impaired BRT with the ankle brace for ROM restriction in the settings: unrestricted (p<0.001), fixed at 15° plantar flexion (p<0.001) and 15°/50° dorsal/plantar flexion (p<0.001) as compared to the control group. BRT was not impaired with the brace for ankle instabilities or the elastic ankle bandage. In conclusion, right-sided ROM restricting ankle braces involve significant impairment of BRT in healthy participants. No such prolonged BRT was found for an elastic ankle bandage or the ligament brace. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effect of Breakfast Prior to Morning Exercise on Cognitive Performance, Mood and Appetite Later in the Day in Habitually Active Women

PubMed Central

Veasey, Rachel C.; Haskell-Ramsay, Crystal F.; Kennedy, David O.; Tiplady, Brian; Stevenson, Emma J.

2015-01-01

Pre-exercise nutritional practices for active females exercising for mood, cognitive and appetite benefits are not well established. Results from an initial field pilot study showed that higher energy intake at breakfast was associated with lower fatigue and higher overall mood and alertness post-exercise (all p < 0.05). In a follow-up, randomised, controlled trial, 24 active women completed three trials in a balanced, cross-over design. At 0815 h participants completed baseline cognitive tasks, mood and appetite visual analogue scales (VAS) and were administered a cereal breakfast (providing 118 or 236 kcal) or no breakfast. After 45 min, they completed a 30 min run at 65% heart rate reserve (HRR). Parameters were re-assessed immediately after exercise, then hourly until lunch (~1240 h), immediately post-lunch and at 1500 and 1900 h via a mobile phone. Breakfast enhanced feelings of relaxation before lunch (p < 0.05, d > 0.40), though breakfast was detrimental for working memory mid-afternoon (p = 0.019, d = 0.37) and mental fatigue and tension later in the day (all p < 0.05, d > 0.038). Breakfast was also beneficial for appetite control before lunch irrespective of size (all p < 0.05, d > 0.43). These data provide information on pre-exercise nutritional practices for active females and suggest that a small breakfast eaten prior to exercise can benefit post-exercise mood and subjective appetite ratings. PMID:26184302

Photobiomodulation Therapy on Physiological and Performance Parameters During Running Tests: Dose-Response Effects.

PubMed

Dellagrana, Rodolfo André; Rossato, Mateus; Sakugawa, Raphael Luiz; Baroni, Bruno Mafredini; Diefenthaeler, Fernando

2018-02-22

This study was aimed at verifying effects of photobiomodulation therapy (PBMT) with different energy doses (15, 30, and 60 J per site) on physiological and performance parameters during running tests. Fifteen male recreational runners participated in a crossover, randomised, double-blind, and placebo-controlled trial. They performed testing protocol in 5 sessions with different treatments: control, placebo, and PBMT with 15, 30 or 60 J per site (14 sites in each lower limb). Physiological and performance variables were assessed during submaximal (at 8 km·h-1 and 9 km·h-1) and maximal running tests. PBMT with 30 J significantly (p<0.05) improved running economy (RE) at 8 and 9 km·h-1 (3.01% and 3.03%, respectively), rate of perceived exertion (RPE) at 8 km·h-1 (7.86%), velocity at VO2MAX (3.07%), peak of velocity (PV) (1.49%), and total time to exhaustion (TTE) (3.41%) compared to placebo. PBMT with 15 J improved RE at 9 km·h-1 (2.98%), RPE at 8 km·h-1 (4.80%), PV (1.33%), TTE (3.06%), and total distance (4.01%) compared to the placebo; while PBMT with 60 J only increased RE at 9 km·h-1 (3.87%) compared to placebo. All PBMT doses positively affected physiological and/or performance parameters; however magnitude-based inference reported that PBMT applied with 30 J led to more beneficial effects than 15 J and 60 J.

Targeted transcranial theta-burst stimulation alters fronto-insular network and prefrontal GABA.

PubMed

Iwabuchi, Sarina J; Raschke, Felix; Auer, Dorothee P; Liddle, Peter F; Lankappa, Sudheer T; Palaniyappan, Lena

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) has been used worldwide to treat depression. However, the exact physiological effects are not well understood. Pathophysiology of depression involves crucial limbic structures (e.g. insula), and it is still not clear if these structures can be modulated through neurostimulation of surface regions (e.g. dorsolateral prefrontal cortex, DLPFC), and whether rTMS-induced excitatory/inhibitory transmission alterations relate to fronto-limbic connectivity changes. Therefore, we sought proof-of-concept for neuromodulation of insula via prefrontal intermittent theta-burst stimulation (iTBS), and how these effects relate to GABAergic and glutamatergic systems. In 27 healthy controls, we employed a single-blind crossover randomised-controlled trial comparing placebo and real iTBS using resting-state functional MRI and magnetic resonance spectroscopy. Granger causal analysis was seeded from right anterior insula (rAI) to locate individualized left DLPFC rTMS targets. Effective connectivity coefficients within rAI and DLPFC were calculated, and levels of GABA/Glx, GABA/Cr and Glx/Cr in DLPFC and anterior cingulate voxels were also measured. ITBS significantly dampened fronto-insular connectivity and reduced GABA/Glx in both voxels. GABA/Glx had a significant mediating effect on iTBS-induced changes in DLPFC-to-rAI connectivity. We demonstrate modulation of the rAI using targeted iTBS through alterations of excitatory/inhibitory interactions, which may underlie therapeutic effects of rTMS, offering promise for rTMS treatment optimization. Copyright © 2016 Elsevier Inc. All rights reserved.