Evolutions in Commercial Meat Poultry Breeding.

This paper provides a comprehensive overview of the history of commercial poultry breeding, from domestication to the development of science and commercial breeding structures. The development of breeding goals over time, from mainly focusing on production to broad goals, including bird welfare and health, robustness, environmental impact, biological efficiency and reproduction, is detailed. The paper outlines current breeding goals, including traits (e.g., on foot and leg health, contact dermatitis, gait, cardiovascular health, robustness and livability), recording techniques, their genetic basis and how trait these antagonisms, for example, between welfare and production, are managed. Novel areas like genomic selection and gut health research and their current and potential impact on breeding are highlighted. The environmental impact differences of various genotypes are explained. A future outlook shows that balanced, holistic breeding will continue to enable affordable lean animal protein to feed the world, with a focus on the welfare of the birds and a diversity of choice for the various preferences and cultures across the world.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial.

AIM: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). METHOD: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18-70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). RESULTS: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately -0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (-0.03 points; 95% CI -0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; -0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. CONCLUSION: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches.

Use of cast immobilization versus removable brace in adults with an ankle fracture: two-year follow-up of a multicentre randomized controlled trial.

The aim of this study was to compare the longer-term outcomes of operatively and nonoperatively managed patients treated with a removable brace (fixed-angle removable orthosis) or a plaster cast immobilization for an acute ankle fracture. This is a secondary analysis of a multicentre randomized controlled trial comparing adults with an acute ankle fracture, initially managed either by operative or nonoperative care. Patients were randomly allocated to receive either a cast immobilization or a fixed-angle removable orthosis (removable brace). Data were collected on baseline characteristics, ankle function, quality of life, and complications. The Olerud-Molander Ankle Score (OMAS) was the primary outcome which was used to measure the participant's ankle function. The primary endpoint was at 16 weeks, with longer-term follow-up at 24 weeks and two years. Overall, 436 patients (65%) completed the final two-year follow-up. The mean difference in OMAS at two years was -0.3 points favouring the plaster cast (95% confidence interval -3.9 to 3.4), indicating no statistically significant difference between the interventions. There was no evidence of differences in patient quality of life (measured using the EuroQol five-dimension five-level questionnaire) or Disability Rating Index. This study demonstrated that patients treated with a removable brace had similar outcomes to those treated with a plaster cast in the first two years after injury. A removable brace is an effective alternative to traditional immobilization in a plaster cast for patients with an ankle fracture.

Randomised controlled trial comparing intraoperative cell salvage and autotransfusion with standard care in the treatment of hip fractures: a protocol for the WHITE 9 study.

INTRODUCTION: People who sustain a hip fracture are typically elderly, frail and require urgent surgery. Hip fracture and the urgent surgery is associated with acute blood loss, compounding patients' pre-existing comorbidities including anaemia. Approximately 30% of patients require a donor blood transfusion in the perioperative period. Donor blood transfusions are associated with increased rates of infections, allergic reactions and longer lengths of stay. Furthermore, there is a substantial cost associated with the use of donor blood. Cell salvage and autotransfusion is a technique that recovers, washes and transfuses blood lost during surgery back to the patient. The objective of this study is to determine the clinical and cost effectiveness of intraoperative cell salvage, compared with standard care, in improving health related quality-of-life of patients undergoing hip fracture surgery. METHODS AND ANALYSIS: Multicentre, parallel group, two-arm, randomised controlled trial. Patients aged 60 years and older with a hip fracture treated with surgery are eligible. Participants will be randomly allocated on a 1:1 basis to either undergo cell salvage and autotransfusion or they will follow the standard care pathway. Otherwise, all care will be in accordance with the National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in the primary endpoint: EuroQol-5D-5L HRQoL at 4 months post injury. Secondary outcomes will include complications, postoperative delirium, residential status, mobility, allogenic blood use, mortality and resource use. ETHICS AND DISSEMINATION: NHS ethical approval was provided on 14 August 2019 (19/WA/0197) and the trial registered (ISRCTN15945622). After the conclusion of this trial, a manuscript will be prepared for peer-review publication. Results will be disseminated in lay form to participants and the public. TRIAL REGISTRATION NUMBER: ISRCTN15945622.

Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN' (REGAIN): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge. TRIAL DESIGN: Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation. PARTICIPANTS: Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends. EXCLUSION CRITERIA: 1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study. INTERVENTION AND COMPARATOR: Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care). MAIN OUTCOMES: The primary outcome is health-related quality of life (HRQoL) - PROMIS® 29+2 Profile v2.1 (PROPr) - measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation. RANDOMISATION: Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system. BLINDING (MASKING): To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm. TRIAL STATUS: Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021. TRIAL REGISTRATION: ISRCTN:11466448 , 23rd November 2020 FULL PROTOCOL: The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

A randomized double-blinded sham-controlled cross-over trial of tined-lead sacral nerve stimulation testing for chronic constipation.

OBJECTIVES: Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation. PATIENTS AND METHODS: A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months. RESULTS: A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe. CONCLUSION: ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection.

Cast versus functional brace in the rehabilitation of patients treated for an ankle fracture: protocol for the UK study of ankle injury rehabilitation (AIR) multicentre randomised trial.

INTRODUCTION: Each year in the UK over 120 000 people fracture their ankle. It is not known what the best rehabilitation strategy is for these people. Traditionally standard care has involved immobilisation in a plaster cast but an alternative is a functional brace, which can be removed to allow early movement. This paper details the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with an ankle fracture. METHODS AND ANALYSIS: We will recruit adults with a fractured ankle, for which the treating clinician would consider plaster cast to be a reasonable management option. Randomisation will be on a 1:1 basis, stratified by centre, operative or non-operative management and age. Participants will be allocated to either plaster cast or a functional brace, both treatments are widely used. To have 90% power to detect a difference of 10 points on the primary outcome (Olerud and Molander Ankle Score) at the primary outcome time point (16 weeks), we need to randomise a minimum of 478 people. Quality of life and resource use will be collected at 6, 10, 16, 24 weeks and 12, 18, 24 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The economic evaluation will adhere to the recommendations of the National Institute for Health and Care Excellence reference case. ETHICS, REGISTRATION AND DISSEMINATION: National Research Ethic Committee approved this study on 4 July 2017 (17/WM/0239). The first site opened to recruitment 9 October 2017. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice. TRIAL REGISTRATION NUMBER: ISRCTN15537280; Pre-results.

Colorectal cancer with Synchronous liver-limited Metastases: the protocol of an Inception Cohort study (CoSMIC).

INTRODUCTION: Colorectal cancer is the fourth most common cancer in the UK and an important cause of cancer-related death. In 20% of patients, there is metastasis to the liver or beyond at the time of diagnosis. The management of synchronous disease is complex. Conventional surgery removes the colorectal primary first, followed by chemotherapy, with resection of liver metastases as a final step. Advances in the availability and safety of liver surgery, anaesthesia and critical care have made two alternative options feasible. The first is synchronous resection of the primary and liver metastases. The second is resection of the metastatic disease as the first step, termed the reverse or liver-first approach. Currently, evidence is inadequate to inform the selection of care pathway for patients with colorectal cancer and synchronous liver-limited metastases. Specifically, optimal pathways are not defined and there is a dearth of prospectively recorded cohort-defining factors influencing treatment selection or outcome. METHODS AND ANALYSIS: Colorectal cancer with Synchronous liver-limited Metastases: an Inception Cohort (CoSMIC) is an inception cohort study of patients with a new diagnosis of colorectal cancer with synchronous liver-limited metastases. The sequence of treatment received, and factors influencing treatment decisions, will be evaluated against European Society of Medical Oncology guidelines. Clinical data will be collected, and quality of life, morbidity, mortality and long-term outcome compared for different treatment sequences adjusted for prognostic factors. Disease-free survival or progression will be measured at 1, 2 and 5 years. A nested qualitative study will ascertain patient experiences and clinician perspectives on delivery of care. ETHICS AND DISSEMINATION: The full study protocol was independently peer reviewed by Professor Kees de Jong (University of Maastricht, Holland). CoSMIC has ethical approval from the National Health Service Research Ethics Committee (14/NW/1397). Results will be disseminated to healthcare professionals and patient groups, and may be used to design a definitive trial addressing areas of equipoise in treatment pathways, as well as optimising current pathways to improve outcomes and experiences. TRIAL REGISTRATION NUMBER: NCT02456285, pre-results.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3-5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. FINDINGS: Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9-30·1), p=0·001. INTERPRETATION: Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. FUNDING: NIHR Health Technology Assessment Programme.

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: study protocol for a randomised controlled trial.

BACKGROUND: Constipation affects up to 20% of adults. Chronic constipation (CC) affects 1-2% of adults. Patient dissatisfaction is high; nearly 80% feel that laxative therapy is unsatisfactory and symptoms have significant impact on quality of life. There is uncertainty about the value of specialist investigations and whether equipment-intensive therapies using biofeedback confer additional benefit when compared with specialist conservative advice. METHODS/DESIGN: A three-arm, parallel-group, multicentre randomised controlled trial. OBJECTIVES: to determine whether standardised specialist-led habit training plus pelvic floor retraining using computerised biofeedback is more clinically effective than standardised specialist-led habit training alone; to determine whether outcomes are improved by stratification based on prior investigation of anorectal and colonic pathophysiology. Primary outcome measure is response to treatment, defined as a 0.4-point (10% of scale) or greater reduction in Patient Assessment of Constipation-Quality of Life (PAC-QOL) score 6 months after the end of treatment. Other outcomes up to 12 months include symptoms, quality of life, health economics, psychological health and qualitative experience. HYPOTHESES: (1) habit training (HT) with computer-assisted direct visual biofeedback (HTBF) results in an average reduction in PAC-QOL score of 0.4 points at 6 months compared to HT alone in unselected adults with CC, (2) stratification to either HT or HTBF informed by pathophysiological investigation (INVEST) results in an average 0.4-point reduction in PAC-QOL score at 6 months compared with treatment not directed by investigations (No-INVEST). Inclusion: chronic constipation in adults (aged 18-70 years) defined by self-reported symptom duration of more than 6 months; failure of previous laxatives or prokinetics and diet and lifestyle modifications. Consenting participants (n = 394) will be randomised to one of three arms in an allocation ratio of 3:3:2: [1] habit training, [2] habit training and biofeedback or [3] investigation-led allocation to one of these arms. Analysis will be on an intention-to-treat basis. DISCUSSION: This trial has the potential to answer some of the major outstanding questions in the management of chronic constipation, including whether costly invasive tests are warranted and whether computer-assisted direct visual biofeedback confers additional benefit to well-managed specialist advice alone. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN11791740. Registered on 16 July 2015.

Biodegradable stent or balloon dilatation for benign oesophageal stricture: pilot randomised controlled trial.

AIM: To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in patients with strictures. METHODS: This British multi-site study recruited seventeen symptomatic adult patients with refractory strictures. Patients were randomised using a multicentre, blinded assessor design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The primary endpoint was the average dysphagia score during the first 6 mo. Secondary endpoints included repeat endoscopic procedures, quality of life, and adverse events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses explored alternative estimation methods for dysphagia and multiple imputation of missing values. Nonparametric tests were used. RESULTS: Although both groups improved, the average dysphagia scores for patients receiving stents were higher after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under different estimation methods. Use of additional endoscopic procedures and quality of life (QALY) estimates were similar for BS and ED patients at 6 and 12 mo. Concomitant use of gastrointestinal prescribed medication was greater in the stent group (BS 5.1, ED 2.0 prescriptions; P < 0.001), as were related adverse events (BS 1.4, ED 0.0 events; P = 0.024). Groups were comparable at baseline and findings were statistically significant but numbers were small due to under-recruitment. The oesophageal tract has somatic sensitivity and the process of the stent dissolving, possibly unevenly, might promote discomfort or reflux. CONCLUSION: Stenting was associated with greater dysphagia, co-medication and adverse events. Rigorously conducted and adequately powered trials are needed before widespread adoption of this technology.

Antioxidant therapy does not reduce pain in patients with chronic pancreatitis: the ANTICIPATE study.

BACKGROUND & AIMS: We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. METHODS: We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol. RESULTS: After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, ß-carotene, and selenium were increased significantly in the antioxidant group. CONCLUSIONS: Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants.

Relaxation therapies for the management of primary hypertension in adults.

BACKGROUND: Lifestyle interventions are often recommended as initial treatment for mild hypertension, but the efficacy of relaxation therapies is unclear. OBJECTIVES: To evaluate the effects of relaxation therapies on cardiovascular outcomes and blood pressure in people with elevated blood pressure. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. INCLUSION CRITERIA: RCTs of a parallel design comparing relaxation therapies with no active treatment, or sham therapy; follow-up >/=8 weeks; participants over 18 years, with raised systolic blood pressure (SBP) >/=140 mmHg or diastolic blood pressure (DBP) >/=85 mmHg); SBP and DBP reported at end of follow-up. EXCLUSION CRITERIA: participants were pregnant; participants received antihypertensive medication which changed during the trial. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: 29 RCTs, with eight weeks to five years follow-up, met our inclusion criteria; four were excluded from the primary meta-analysis because of inadequate outcome data. The remaining 25 trials assessed 1,198 participants, but adequate randomisation was confirmed in only seven trials and concealment of allocation in only one. Only one trial reported deaths, heart attacks and strokes (one of each). Meta-analysis indicated that relaxation resulted in small, statistically significant reductions in SBP (mean difference: -5.5 mmHg, 95% CI: -8.2 to -2.8, I2 =72%) and DBP (mean difference: -3.5 mmHg, 95% CI: -5.3 to -1.6, I2 =75%) compared to control. The substantial heterogeneity between trials was not explained by duration of follow-up, type of control, type of relaxation therapy or baseline blood pressure. The nine trials that reported blinding of outcome assessors found a non-significant net reduction in blood pressure (SBP mean difference: -3.2 mmHg, 95% CI: -7.7 to 1.4, I(2) =69%) associated with relaxation. The 15 trials comparing relaxation with sham therapy likewise found a non-significant reduction in blood pressure (SBP mean difference: -3.5 mmHg, 95% CI: -7.1 to 0.2, I(2) =63%). AUTHORS' CONCLUSIONS: In view of the poor quality of included trials and unexplained variation between trials, the evidence in favour of causal association between relaxation and blood pressure reduction is weak. Some of the apparent benefit of relaxation was probably due to aspects of treatment unrelated to relaxation.

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis.

BACKGROUND: Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline. RESULTS: Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. CONCLUSIONS: This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.

Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials.

PURPOSE: To quantify effectiveness of lifestyle interventions for hypertension. DATA SOURCES: Electronic bibliographic databases from 1998 onwards, existing guidelines, systematic reviews. STUDY SELECTION AND DATA ABSTRACTION: We included randomized, controlled trials with at least 8 weeks' follow-up, comparing lifestyle with control interventions, enrolling adults with blood pressure at least 140/85 mmHg. Primary outcome measures were systolic and diastolic blood pressure. Two independent reviewers selected trials and abstracted data; differences were resolved by discussion. RESULTS: We categorized trials by type of intervention and used random effects meta-analysis to combine mean differences between endpoint blood pressure in treatment and control groups in 105 trials randomizing 6805 participants. Robust statistically significant effects were found for improved diet, aerobic exercise, alcohol and sodium restriction, and fish oil supplements: mean reductions in systolic blood pressure of 5.0 mmHg [95% confidence interval (CI): 3.1-7.0], 4.6 mmHg (95% CI: 2.0-7.1), 3.8 mmHg (95% CI: 1.4-6.1), 3.6 mmHg (95% CI: 2.5-4.6) and 2.3 mmHg (95% CI: 0.2-4.3), respectively, with corresponding reductions in diastolic blood pressure. Relaxation significantly reduced blood pressure only when compared with non-intervention controls. We found no robust evidence of any important effect on blood pressure of potassium, magnesium or calcium supplements. CONCLUSIONS: Patients with elevated blood pressure should follow a weight-reducing diet, take regular exercise, and restrict alcohol and salt intake. Available evidence does not support relaxation therapies, calcium, magnesium or potassium supplements to reduce blood pressure.