Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG-AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease.

On page 1072 in the originally published version of this article, PS2 was a typo and should have read PS3 in the following sentence: ''The other most common examples of modified strength included the following: PVS1 (a predicted null variant in a gene where LOF is a known mechanism of disease) was downgraded from very strong four times, PS2 (well-established functional studies show a deleterious effect) was downgraded three times, and BS1 (MAF is too high for the disorder) was downgraded three times.'' The error has been corrected online, and the authors apologize for the oversight.

Objectives STRIDE assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. Methods A multi-site, parallel, two-arm randomized controlled trial in community settings and an integrated health plan. Inclusion criteria: Age ≥18; taking antipsychotic medication for ≥30 days; BMI ≥27. Exclusions: significant cognitive impairment; pregnancy/breastfeeding; recent psychiatric hospitalization, bariatric surgery, cancer, heart attack or stroke. The intervention emphasized moderate caloric reduction, DASH diet, and physical activity. Blinded staff collected data at baseline, 6, and 12 months. Results Participants (56 men, 144 women), mean age = 47.2(SD =10.6), were randomized to usual care (n =96) or a 6-month weekly group intervention plus 6 monthly maintenance sessions (n =104). 181 participants (90.5%) completed 6-month, and 170 (85%) completed 12-month assessments, without differential attrition. Participants attended 14.5 of 24 sessions over 6 months. Intent-to-treat analyses found intervention participants lost 4.4 kg more than control participants from baseline to 6 months (95% CI [−6.96 kg, −1.78 kg]), and 2.6 kg more than controls (95% CI −5.14 kg, −0.07 kg] from baseline to 12 months. At 12 months, fasting glucose levels in controls had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in intervention participants, from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study-related; medical hospitalizations were reduced in the intervention group (6.7%) compared to controls (18.8%)(χ2= 6.66, p = 0.01). Conclusions Individuals taking antipsychotic medications can lose weight and improve fasting glucose levels. Increasing reach of the intervention is an important future step. Funding Source National Institute of Diabetes and Digestive and Kidney Diseases, Grant R18DK076775 Trial Registration Clinical Trials.gov, NCT00790517; http://clinicaltrials.gov/ct2/show/NCT00790517?term=STRIDE&rank=1

Objective-This study was designed to compare the initial efficacy of Motivational Interviewing (MI), Online Transtheoretical Model (TTM) Tailored communications and a brief Health Risk Intervention (HRI) on four health risk factors (inactivity, BMI, stress and smoking) in a worksite sample.Method-A randomized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments. The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months. At the initial post-treatment assessment at six months, groups were compared on the percentage who had progressed from at-risk to taking effective action on each of the four risks.Results-Compared to the HRI only group, the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months. MI and TTM group outcomes were not different. Conclusion: This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes. Future research will examine the long-term impacts of each treatment, their cost effectiveness, effects on productivity and quality of life, and process variables mediating outcomes. KeywordsMultiple behavior change; Motivational Interviewing; TTM Tailoring; exercise; stress; smoking; BMI Increasingly it is recognized that a major barrier to dissemination of evidence-based health promotion programs is that most programs were not designed or developed to reach at-risk populations (Glasgow et al., 2003). They were designed for and evaluated on self-selected samples of at-risk individuals. For example, in the United States Public Health Services Corresponding Author: James O. Prochaska, Ph.D., Cancer Prevention Research Center, 2 Chafee Road, University of Rhode Island, Kingston, RI 02881, Tel: 401-874-2830, Fax: 401-874-5562, jop@uri.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1996 Clinical Guidelines for the Treatment of Tobacco, over 3,000 studies on tobacco were identified. The Guidelines were able to recommend a broad range of evidence-based interventions for motivated smokers; i.e., those prepared to quit in the next month (Fiore et al., 1996). There were no evidence-based interventions recommended for unmotivated smokers, even though they make up more than 80% of all U.S. smokers (Velicer et al., 1995) and more than 90% of daily smokers (Wewers et al., 2003). In the second edition of the Guidelines there w...

Objective Observational studies suggest that minimal gestational weight gain (GWG) may optimize pregnancy outcomes for obese women. This trial tested the efficacy of a group-based weight management intervention for limiting GWG among obese women. Methods We randomized 114 obese women (BMI [mean±SD] 36.7±4.9 kg/m2) between 7–21 weeks’ (14.9±2.6) gestation to intervention (n=56) or usual care control conditions (n=58). The intervention included individualized calorie goals, advice to maintain weight within 3% of randomization and follow the Dietary Approaches to Stop Hypertension dietary pattern without sodium restriction, and attendance at weekly group meetings until delivery. Control participants received one-time dietary advice. Our three main outcomes were maternal weight change from randomization to 2 weeks postpartum and from randomization to 34 weeks gestation, and newborn large-for-gestational age (birth weight >90th percentile, LGA). Results Intervention participants gained less weight from randomization to 34 weeks gestation (5.0 vs 8.4 kg, mean difference=−3.4 kg, 95% CI [−5.1, −1.8]), and from randomization to 2 weeks postpartum (−2.6 vs +1.2 kg, mean difference=−3.8 kg, 95% CI [−5.9, −1.7]). They also had a lower proportion of LGA babies (9% vs. 26%, odds ratio=0.28, 95% CI [0.09, 0.84]). Conclusions The intervention resulted in lower GWG and lower prevalence of LGA newborns.