Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function

Muscle glycogen utilisation during Rugby match play: Effects of pre-game carbohydrate

Objectives: Although the physical demands of Rugby League (RL) match-play are well-known, the fuel sources supporting energy-production are poorly understood. We therefore assessed muscle glycogen utilisation and plasma metabolite responses to RL match-play after a relatively high (HCHO) or relatively low CHO (LCHO) diet. Design: Sixteen (mean ± SD age; 18 ± 1 years, body-mass; 88 ± 12 kg, height 180 ± 8 cm) professional players completed a RL match after 36-h consuming a non-isocaloric high carbohydrate (n = 8; 6 g kg day−1) or low carbohydrate (n = 8; 3 g kg day−1) diet. Methods: Muscle biopsies and blood samples were obtained pre- and post-match, alongside external and internal loads quantified using Global Positioning System technology and heart rate, respectively. Data were analysed using effects sizes ±90% CI and magnitude-based inferences. Results: Differences in pre-match muscle glycogen between high and low carbohydrate conditions (449 ± 51 and 444 ± 81 mmol kg−1 d.w.) were unclear. High (243 ± 43 mmol kg−1 d.w.) and low carbohydrate groups (298 ± 130 mmol kg−1 d.w.) were most and very likely reduced post-match, respectively. For both groups, differences in pre-match NEFA and glycerol were unclear, with a most likely increase in NEFA and glycerol post-match. NEFA was likely lower in the high compared with low carbohydrate group post-match (0.95 ± 0.39 mmol l−1 and 1.45 ± 0.51 mmol l−1, respectively), whereas differences between the 2 groups for glycerol were unclear (98.1 ± 33.6 mmol l−1 and 123.1 ± 39.6 mmol l−1) in the high and low carbohydrate groups, respectively. Conclusions: Professional RL players can utilise ∼40% of their muscle glycogen during a competitive match regardless of their carbohydrate consumption in the preceding 36-h

Energy intake and expenditure assessed ‘in-season’ in an elite European rugby union squad.

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Sport Science on 09/06/2015, available online: http://www.tandfonline.com/doi/pdf/10.1080/17461391.2015.1042528Rugby union (RU) is a complex high-intensity intermittent collision sport with emphasis placed on players possessing high lean body mass and low body fat. After an 8 to 12-week pre-season focused on physiological adaptations, emphasis shifts towards competitive performance. However, there are no objective data on the physiological demands or energy intake (EI) and energy expenditure (EE) for elite players during this period. Accordingly, in-season training load using global positioning system and session rating of perceived exertion (sRPE), alongside six-day assessments of EE and EI were measured in 44 elite RU players. Mean weekly distance covered was 7827 ± 954 m and 9572 ± 1233 m with a total mean weekly sRPE of 1776 ± 355 and 1523 ± 434 AU for forwards and backs, respectively. Mean weekly EI was 16.6 ± 1.5 and 14.2 ± 1.2 megajoules (MJ) and EE was 15.9 ± 0.5 and 14 ± 0.5 MJ. Mean carbohydrate (CHO) intake was 3.5 ± 0.8 and 3.4 ± 0.7 g.kg-1 body mass, protein intake was 2.7 ± 0.3 and 2.7 ± 0.5 g.kg-1 body mass, and fat intake was 1.4 ± 0.2 and 1.4 ± 0.3 g.kg-1 body mass. All players who completed the food diary self-selected a 'low' CHO 'high' protein diet during the early part of the week, with CHO intake increasing in the days leading up to a match, resulting in the mean EI matching EE. Based on EE and training load data, the EI and composition seems appropriate, although further research is required to evaluate if this diet is optimal for match day performance

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Protocol for developing quality assurance measures to use in surgical trials:an example from the ROMIO study

INTRODUCTION: Randomised controlled trials (RCTs) in surgery are frequently criticised because surgeon expertise and standards of surgery are not considered or accounted for during study design. This is particularly true in pragmatic trials (which typically involve multiple centres and surgeons and are based in 'real world' settings), compared with explanatory trials (which are smaller and more tightly controlled).OBJECTIVE: This protocol describes a process to develop and test quality assurance (QA) measures for use within a predominantly pragmatic surgical RCT comparing minimally invasive and open techniques for oesophageal cancer (the NIHR ROMIO study). It builds on methods initiated in the ROMIO pilot RCT.METHODS AND ANALYSIS: We have identified three distinct types of QA measure: (i) entry criteria for surgeons, through assessment of operative videos, (ii) standardisation of operative techniques (by establishing minimum key procedural phases) and (iii) monitoring of surgeons during the trial, using intraoperative photography to document key procedural phases and standardising the pathological assessment of specimens. The QA measures will be adapted from the pilot study and tested iteratively, and the video and photo assessment tools will be tested for reliability and validity.ETHICS AND DISSEMINATION: Ethics approval was obtained (NRES Committee South West-Frenchay, 25 April 2016, ref: 16/SW/0098). Results of the QA development study will be submitted for publication in a peer-reviewed journal.Trial registration number: ISRCTN59036820, ISRCTN10386621.</p

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]