Background: Remote ischemic preconditioning (RIPC) is a method of preparing the body for a later prolonged ischemic episode to protect against subsequent detrimental effects. This study aimed to identify the effects of RIPC in vascular surgery. Methods: A standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses search was conducted of randomized controlled trials of RIPC in patients undergoing open or endovascular aneurysm repair, carotid endarterectomy, or lower limb bypass reporting on mortality and renal or cardiac outcomes. Random-effects meta-analysis was performed using Review Manager 5.3 (The Nordic Cochrane Center, Copenhagen, Denmark). Results: A total of 13 randomized controlled trials in the meta-analysis included 548 patients in the RIPC cohort and 549 controls. There was no significant difference in mortality, renal dysfunction, myocardial infarction, myocardial injury, or length of stay between the groups, with subgroup and sensitivity analysis showing no significant difference. Conclusions: Current evidence demonstrates no benefit of RIPC in vascular surgery. Further large multicenter trials of RIPC in major vascular surgery should be considered.

Additional file 3. Three-period three-treatment sample size calculation code (Stata ado file).

Background Crossover designs are commonly utilised in randomised controlled trials investigating treatments for long-term chronic illnesses. One problem with this design is its inherent repeated measures necessitate the availability of an estimate of the within-person standard deviation (SD) to perform a sample size calculation, which may be rarely available at the design stage of a trial. Interim sample size re-estimation designs can be used to help alleviate this issue by adapting the sample size mid-way through the trial, using accrued information in a statistically robust way. Methods The AIM HY-INFORM study is part of the Informative Markers in Hypertension (AIM HY) Programme and comprises two crossover trials, each with a planned recruitment of 600 participants. The objective of the study is to test whether blood pressure response to first line antihypertensive treatment depends on ethnicity. An interim analysis is planned to reassess the assumptions of the planned sample size for the study. The aims of this paper are: (1) to provide a formula for sample size re-estimation in both crossover trials; and (2) to present a simulation study of the planned interim analysis to investigate alternative within-person SDs to that assumed. Results The AIM HY-INFORM protocol sample size calculation fixes the within-person SD to be 8 mmHg, giving > 90% power for a primary treatment effect of 4 mmHg. Using the method developed here and simulating the interim sample size reassessment, if we were to see a larger within-person SD of 9 mmHg at interim, 640 participants for 90% power 90% of the time in the three-period three-treatment design would be required. Similarly, in the four-period four-treatment crossover design, 602 participants would be required. Conclusions The formulas presented here provide a method for re-estimating the sample size in crossover trials. In the context of the AIM HY-INFORM study, simulating the interim analysis allows us to explore the results of a possible increase in the within-person SD from that assumed. Simulations show that without increasing the planned sample size of 600 participants, we can reasonably still expect to achieve 80% power with a small increase in the within-person SD from that assumed. Trial registration ClinicalTrials.gov, NCT02847338 . Registered on 28 July 2016.

Background: Ethnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of antihypertensive therapies. Current UK guidelines use a "black versus white" approach; in doing so, they ignore the United Kingdom's largest ethnic minority: Asians from South Asia. Study design: The primary purpose of the AIM-HY INFORM trial is to identify potential differences in response to antihypertensive drugs used as mono- or dual therapy on the basis of self-defined ethnicity. A multicenter, prospective, open-label, randomized study with 2 parallel, independent trial arms (mono- and dual therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od; amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32 weeks. Equal numbers of 3 ethnic groups (white, black/black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (ie, 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured 8 weeks after each treatment period begins will serve as the primary outcome measure. Conclusion: AIM-HY INFORM is a prospective, open-label, randomized trial which aims to evaluate first- and second-line antihypertensive therapies for multiethnic populations. (C) 2018 The Authors. Published by Elsevier Inc.

OBJECTIVE: A post-hoc exploratory analysis of all subjects from the phase 2 MS-STAT trial in secondary progressive MS (SPMS) to determine the relationship between baseline brain volume and atrophy rate with measured clinical parameters. BACKGROUND: The 2 year MS-STAT trial using high dose simvastatin (80mg) versus placebo, demonstrated a 43[percnt] annualised reduction in whole-brain atrophy rate with indications of effect on both clinician and patient-observed disability outcomes. DESIGN/METHODS:Linear regression was used to examine the associations between brain volume and clinical outcomes (Expanded Disability Status Scale [EDSS]; 9 Hole Peg Test, 25ft walk, Paced Auditory Serial Addition Test [PASAT]: components of the MS Functional Composite [MSFC]). In all models the clinical outcomes, or change in clinical outcome was treated as the dependent variable with baseline brain volume or brain atrophy rate included as the predictor variable of interest. All models were adjusted for potential confounders. RESULTS:At baseline, smaller brain volume was associated with slower 25ft walk speed, 9 Hole Peg test and lower PASAT scores. Greater whole brain atrophy was associated with increasing (worsening) EDSS and 25ft walk test slowing, but not associated with change in 9 Hole Peg test or PASAT. A 1[percnt] per year higher atrophy rate was associated with 0.24 points increase in EDSS, and 0.57 ft/s slowing of walk speed. In addition, 1[percnt] per year higher atrophy rate between baseline and 12 months was predictive of 0.17 points increase in EDSS between 12 and 25 months. CONCLUSIONS: Both baseline brain volume and change in brain volume, demonstrate important associations with clinical parameters, supporting the use of brain atrophy rate as a suitable biologically plausible outcome for clinical disease progression. Study Supported by:Moulton Foundation, Berkeley Foundation, MSTC, NIHR UCL/UCLH BRC.

The NIHR BioResource–Rare Diseases project is an initiative to perform whole genome sequencing on 10,000 individuals with rare genetic diseases in order to improve our understanding of disease causation.Five studentships jointly supervised by collaborators of the NIHR BioResource at the University of Cambridge and members of the MRC Biostatistics Unit are available to develop and apply statistical methodology to support this initiative:

The introduction of measurement into medicine established the foundations of the modern discipline of biostatistics, crucial to all aspects of medicine, epidemiology and public health. But how did statistics become so embedded? Isabel Baker looks back at Professor Major Greenwood, an eminent statistician of the 20th century, who developed and encouraged some of the first uses of modern statistical methods in medical science.This 1920s photo of Major Greenwood―whose forename was Major, rather than reflecting military rank―pictures him smiling cheerily on a wooden bench. But it gives little away about the nature of this distinguished and imposing man who dedicated his life’s work to statistics.

The BSU is an internationally recognised research unit specialising in statistical modelling with application to medical, biological or public health sciences. Details of the work carried out in the Unit appear on our website http://www. mrc-bsu. cam. ac. uk.

A paradigm shift is occurring in the treatment of heroin overdose. On 5 November the World Health Organization launched guidelines on the community management of heroin and opioid overdose and emergency administration of naloxone by people who are not medically trained. 1 Historically, naloxone has been used only in hospitals and by ambulance workers to reverse the effects of an opioid overdose. Today, several countries are providing emergency naloxone to patients, their families, and other potential non-medical first responders.This is important because these overdoses contribute substantially to drug related deaths worldwide, with an estimated 69 000 people dying from opioid overdose each year. 1 Of nearly 3000 drug related deaths registered in England and Wales in 2013, more than half (56%) involved opioids. 2 Last month Scotland (the first country to introduce a national programme to provide …