A systematic review of the effectiveness of school-based obesity prevention programmes for First Nations, Inuit and Métis youth in Canada.

First Nations, Inuit and Métis (FNIM) youth are disproportionately affected by obesity and represent known a high-risk group in Canada. School-based prevention programmes may have the potential to effectively influence obesity-related health behaviours (i.e. healthy eating and physical activity) among this population. We conducted a systematic review of nine electronic databases (2003-2014) to identify studies that describe school-based programmes that have been developed to improve obesity-related health behaviours and outcomes among FNIM youth in Canada. The objectives of this review were to identify and evaluate the effectiveness of these programmes and assess the strength of the methodologies used to evaluate them. Fifteen studies, representing seven distinct interventions, met our inclusion criteria. The majority of these programmes did not result in significant improvements in outcomes related to obesity, healthy eating, or physical activity among FNIM youth. The studies varied in design rigour and use of evaluation activities. The lack of literature on effective school-based programmes for FNIM youth in Canada that target obesity-related outcomes highlights a priority area for future intervention development, evaluation and dissemination within the peer-reviewed literature. Further research is needed on interventions involving Métis and Inuit youth, secondary school-aged FNIM youth and FNIM youth living in urban settings.

Design and execution of clinical trials in orthopaedic surgery.

High-quality randomised controlled trials (RCTs) evaluating surgical therapies are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic clinical trials have unique challenges; however, when these challenges are overcome, evidence from trials can be definitive in its impact on surgical practice. In this review, we highlight several issues that pose potential challenges to orthopaedic investigators aiming to perform surgical randomised controlled trials. We begin with a discussion on trial design issues, including the ethics of sham surgery, the importance of sample size, the need for patient-important outcomes, and overcoming expertise bias. We then explore features surrounding the execution of surgical randomised trials, including ethics review boards, the importance of organisational frameworks, and obtaining adequate funding. Cite this article: Bone Joint Res 2014;3:161-8.

[Radical cystectomy - pro laparoscopic]. / Radikale Zystektomie - pro laparoskopisch.

Although the technical feasibility of laparoscopic radical cystectomy (LRC) has been proven and the procedure has been accepted in the EAU guidelines 2011 as a valid alternative, its actual position has to be determined. On the one hand the advantages of LRC (less blood loss, lower transfusion rates, shorter analgesia time) have been proven in retrospective studies; however, the technical difficulties of purely laparoscopic urinary diversion result in very long operating times and in cases of a laparoscopic-assisted creation of a neobladder, the question of the advantage of this approach remains doubtful. Despite case reports of port metastases and peritoneal carcinosis following laparoscopic and robot-assisted radical cystectomy, there is no difference in terms of oncological long-term data (up to 10 years) between laparoscopy and open surgery performed at centres of excellence. Evidently, the curative options for the patients do not depend on the type of surgery (open versus minimally invasive) but on the efficacy of adjuvant treatment strategies (polychemotherapy). Currently it is believed that LRC should be considered for patients with low risk of progression (pT1-2). The final position of laparoscopic radical cystectomy can only be evaluated in a multicentric randomized controlled trial.

Detailed computational study of p53 and p16: using evolutionary sequence analysis and disease-associated mutations to predict the functional consequences of allelic variants.

Deciding whether a missense allelic variant affects protein function is important in many contexts. We previously demonstrated that a detailed analysis of p53 intragenic conservation correlates with somatic mutation hotspots. Here we refine these evolutionary studies and expand them to the p16/Ink4a gene. We calculated that in order for 'absolute conservation' of a codon across multiple species to achieve P<0.05, the evolutionary substitution database must contain at least 3(M) variants, where M equals the number of codons in the gene. Codons in p53 were divided into high (73% of codons), intermediate (29% of codons), and low (0 codons) likelihood of being mutation hotspots. From a database of 263 somatic missense p16 mutations, we identified only four codons that are mutational hotspots at P<0.05 (8 mutations). However, data on function, structure, and disease association support the conclusion that 11 other codons with > or =5 somatic mutations also likely indicate functionally critical residues, even though P0.05. We calculated p16 evolution using amino acid substitution matrices and nucleotide substitution distances. We looked for evolutionary parameters at each codon that would predict whether missense mutations were disease associated or disrupted function. The current p16 evolutionary substitution database is too small to determine whether observations of 'absolute conservation' are statistically significant. Increasing the number of sequences from three to seven significantly improved the predictive value of evolutionary computations. The sensitivity and specificity for conservation scores in predicting disease association of p16 codons is 70-80%. Despite the small p16 sequence database, our calculations of high conservation correctly predicted loss of cell cycle arrest function in 75% of tested codons, and low conservation correctly predicted wild-type function in 80-90% of codons. These data validate our hypothesis that detailed evolutionary analyses help predict the consequences of missense amino-acid variants.