PubMed | Institute for Medicine and Public Health and and Vanderbilt University
Type: | Journal: Pediatrics | Year: 2017
The effectiveness of tonsillectomy or adenotonsillectomy (tonsillectomy) for recurrent throat infection compared with watchful waiting is uncertain.To compare sleep, cognitive, behavioral, and health outcomes of tonsillectomy versus watchful waiting in children with recurrent throat infections.MEDLINE, Embase, and the Cochrane Library.Two investigators independently screened studies against predetermined criteria.One investigator extracted data with review by a second. Investigators independently assessed risk of bias and strength of evidence (SOE) and confidence in the estimate of effects.Seven studies including children with 3 infections in the previous 1 to 3 years addressed this question. In studies reporting baseline data, number of infections/sore throats decreased from baseline in both groups, with greater decreases in sore throat days, clinician contacts, diagnosed group A streptococcal infections, and school absences in tonsillectomized children in the short term (<12 months). Quality of life was not markedly different between groups at any time point.Few studies fully categorized infection/sore throat severity; attrition was high.Throat infections, utilization, and school absences improved in the first postsurgical year in tonsillectomized children versus children not receiving surgery. Benefits did not persist over time; longer-term outcomes are limited. SOE is moderate for reduction in short-term throat infections and insufficient for longer-term reduction. SOE is low for no difference in longer-term streptococcal infection reduction. SOE is low for utilization and missed school reduction in the short term, low for no difference in longer-term missed school, and low for no differences in quality of life.
PubMed | Oxford Genetics, Ohio State University, Fred Hutchinson Cancer Research Center, The Charles Bronfman Institute for Personalized Medicine and and 13 more.
Type: Journal Article | Journal: Human molecular genetics | Year: 2016
Although the role of complete gene inactivation by two loss-of-function mutations inherited in trans is well-established in recessive Mendelian diseases, we have not yet explored how such gene knockouts (KOs) could influence complex human phenotypes. Here, we developed a statistical framework to test the association between gene KOs and quantitative human traits. Our method is flexible, publicly available, and compatible with common genotype format files (e.g. PLINK and vcf). We characterized gene KOs in 4498 participants from the NHLBI Exome Sequence Project (ESP) sequenced at high coverage (>100), 1976 French Canadians from the Montreal Heart Institute Biobank sequenced at low coverage (5.7), and >100 000 participants from the Genetic Investigation of ANthropometric Traits (GIANT) Consortium genotyped on an exome array. We tested associations between gene KOs and three anthropometric traits: body mass index (BMI), height and BMI-adjusted waist-to-hip ratio (WHR). Despite our large sample size and multiple datasets available, we could not detect robust associations between specific gene KOs and quantitative anthropometric traits. Our results highlight several limitations and challenges for future gene KO studies in humans, in particular when there is no prior knowledge on the phenotypes that might be affected by the tested gene KOs. They also suggest that gene KOs identified with current DNA sequencing methodologies probably do not strongly influence normal variation in BMI, height, and WHR in the general human population.