IMPORTANCE Overweight and obesity have been associated with adverse health effects. OBJECTIVE To systematically review evidence on benefits and harms of behavioral and pharmacotherapy weight loss and weight loss maintenance interventions in adults to inform the US Preventive Services Task Force.
IMPORTANCE Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States.OBJECTIVE To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC.
Systematic reviewers should consider and be transparent when estimating data from figures when the information cannot be obtained from study authors and perform sensitivity analyses of pooled results to reduce bias.
Family history of colorectal cancer (CRC) is a known risk factor for CRC, and encompasses both genetic and shared environmental risk. We conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening. We found high heterogeneity in family history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC, but no evidence for differential adenoma location or adenoma progression by family history. Limited data on the natural history of CRC by family history suggests a differential age or stage at cancer diagnosis and mixed evidence on tumor location. Adherence to recommended colonoscopy screening was higher in people with family history of CRC. Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future family history may remain a valuable clinical tool for identifying individuals at increased risk of CRC.
PurposeGenome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder allows the possibility of clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource on the clinical relevance of genomic variation for use in precision medicine and research.MethodsWe developed a practical, standardized protocol to identify available evidence and generate qualitative summary reports of actionability for disorders and associated genes. We applied a semi-quantitative metric to score actionability.ResultsWe generated summary reports and actionability scores for the 56 genes and associated disorders recommended by the American College of Medical Genetics and Genomics for return as secondary findings from clinical genome-scale sequencing. We also describe the challenges that arose during the development of the protocol which highlight important issues in characterizing actionability across a range of disorders.ConclusionThe ClinGen framework for actionability assessment will assist research and clinical communities in making clear, efficient, and consistent determinations of actionability based on transparent criteria to guide analysis and reporting of findings from clinical genome-scale sequencing.
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