Key Genes of Lipid Metabolism and WNT-Signaling Are Downregulated in Subcutaneous Adipose Tissue with Moderate Weight Loss.

Smaller cross-sectional studies and bariatric surgery trials suggest that weight loss may change the expression of genes in adipose tissue that have been implicated in the development of metabolic diseases, but well-powered intervention trials are lacking. In post hoc analyses of data from a 12-week dietary intervention trial initially designed to compare metabolic effects of intermittent vs. continuous calorie restriction, we analyzed the effects of overall weight loss on the subcutaneous adipose tissue (SAT) transcriptome. Changes in the transcriptome were measured by microarray using SAT samples of 138 overweight or obese individuals (age range: 35⁻65 years, BMI range: 25⁻40, non-smokers, non-diabetics). Participants were grouped post hoc according to the degree of their weight loss by quartiles (average weight loss in quartiles 1 to 4: 0%, -3.2%, -5.9%, and -10.7%). Candidate genes showing differential expression with weight loss according to microarray analyses were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and fold changes (FCs) were calculated to quantify differences in gene expression. A comparison of individuals in the highest vs. the lowest weight loss quartile revealed 681 genes to be differentially expressed (corrected p < 0.05), with 40 showing FCs of at least 0.4. Out of these, expression changes in secreted frizzled-related protein 2 (SFRP2, FC = 0.65, p = 0.006), stearoyl-CoA desaturase (SCD, FC = -1.00, p < 0.001), and hypoxia inducible lipid droplet-associated (HILPDA, FC = -0.45, p = 0.001) with weight loss were confirmed by RT-qPCR. Dietary weight loss induces significant changes in the expression of genes implicated in lipid metabolism (SCD and HILPDA) and WNT-signaling (SFRP2) in SAT.

Trading certainty for speed - how much uncertainty are decisionmakers and guideline developers willing to accept when using rapid reviews: an international survey.

BACKGROUND: Decisionmakers and guideline developers demand rapid syntheses of the evidence when time sensitive evidence-informed decisions are required. A potential trade-off of such rapid reviews is that their results can have less reliability than results of systematic reviews that can lead to an increased risk of making incorrect decisions or recommendations. We sought to determine how much incremental uncertainty about the correctness of an answer guideline developers and health policy decisionmakers are willing to accept in exchange for a rapid evidence-synthesis. METHODS: Employing a purposive sample, we conducted an international web-based, anonymous survey of decisionmakers and guideline developers. Based on a clinical treatment, a public health, and a clinical prevention scenario, participants indicated the maximum risk of getting an incorrect answer from a rapid review that they would be willing to accept. We carefully reviewed data and performed descriptive statistical analyses. RESULTS: In total, 325 (58.5%) of 556 participants completed our survey and were eligible for analysis. The median acceptable incremental risk for getting an incorrect answer from a rapid review across all three scenarios was 10.0% (interquartile range [IQR] 5.0-15.0). Acceptable risks were similar for the clinical treatment (n = 313, median 10.0% [IQR 5.0-15.0]) and the public health scenarios (n = 320, median 10.0% [IQR 5.0-15.0]) and lower for the clinical prevention scenario (n = 312, median 6.5% [IQR 5.0-10.5]). CONCLUSIONS: Findings suggest that decisionmakers are willing to accept some trade-off in validity in exchange for a rapid review. Nevertheless, they expect the validity of rapid reviews to come close to that of systematic reviews.

Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews.

OBJECTIVES: This study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects. DESIGN: This is a review of systematic reviews. DATA SOURCES: This study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD. METHODS: We dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence. RESULTS: Nineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: -0.35; 95% CI -0.31 to -0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95% CI 1.0 to 3.28).Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95% CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence). CONCLUSIONS: In contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants. TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews (PROSPERO) registration number: 42016035580.