Background: The beneficial effects of flavonoid consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. Objective: We aimed to systematically review the effectiveness of different flavonoid subclasses and flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors—ie, lipoproteins, blood pressure, and flow-mediated dilatation (FMD). Design: Methods included a structured search strategy on MEDLINE, EMBASE, and Cochrane databases; formal inclusion or exclusion, data extraction, and validity assessment; and meta-analysis. Results: One hundred thirty-three trials were included. No randomized controlled trial studied effects on CVD morbidity or mortality. Significant heterogeneity confirmed differential effects between flavonoid subclasses and foods. Chocolate increased FMD after acute (3.99%; 95% CI: 2.86, 5.12; 6 studies) and chronic (1.45%; 0.62, 2.28; 2 studies) intake and reduced systolic (−5.88 mm Hg; −9.55, −2.21; 5 studies) and diastolic (−3.30 mm Hg; −5.77, −0.83; 4 studies) blood pressure. Soy protein isolate (but not other soy products or components) significantly reduced diastolic blood pressure (−1.99 mm Hg; −2.86, −1.12; 9 studies) and LDL cholesterol (−0.19 mmol/L; −0.24, −0.14; 39 studies). Acute black tea consumption increased systolic (5.69 mm Hg; 1.52, 9.86; 4 studies) and diastolic (2.56 mm Hg; 1.03, 4.10; 4 studies) blood pressure. Green tea reduced LDL (−0.23 mmol/L; −0.34, −0.12; 4 studies). For many of the other flavonoids, there was insufficient evidence to draw conclusions about efficacy. Conclusions: To date, the effects of flavonoids from soy and cocoa have been the main focus of attention. Future studies should focus on other commonly consumed subclasses (eg, anthocyanins and flavanones), examine dose-response effects, and be of long enough duration to allow assessment of clinically relevant endpoints.

Objectives To identify and appraise empirical studies on publication and related biases published since 1998; to assess methods to deal with publication and related biases; and to examine, in a random sample of published systematic reviews, measures taken to prevent, reduce and detect dissemination bias. Data sources The main literature search, in August 2008, covered the Cochrane Methodology Register Database, MEDLINE, EMBASE, AMED and CINAHL. In May 2009, PubMed, PsycINFO and OpenSIGLE were also searched. Reference lists of retrieved studies were also examined. Review methods In Part I, studies were classified as evidence or method studies and data were extracted according to types of dissemination bias or methods for dealing with it. Evidence from empirical studies was summarised narratively. In Part II, 300 systematic reviews were randomly selected from MEDLINE and the methods used to deal with publication and related biases were assessed. Results Studies with significant or positive results were more likely to be published than those with non-significant or negative results, thereby confirming findings from a previous HTA report. There was convincing evidence that outcome reporting bias exists and has an impact on the pooled summary in systematic reviews. Studies with significant results tended to be published earlier than studies with non-significant results, and empirical evidence suggests that published studies tended to report a greater treatment effect than those from the grey literature. Exclusion of non-English-language studies appeared to result in a high risk of bias in some areas of research such as complementary and alternative medicine. In a few cases, publication and related biases had a potentially detrimental impact on patients or resource use. Publication bias can be prevented before a literature review (e.g. by prospective registration of trials), or detected during a literature review (e.g. by locating unpublished studies, funnel plot and related tests, sensitivity analysis modelling), or its impact can be minimised after a literature review (e.g. by confirmatory large-scale trials, updating the systematic review). The interpretation of funnel plot and related statistical tests, often used to assess publication bias, was often too simplistic and likely misleading. More sophisticated modelling methods have not been widely used. Compared with systematic reviews published in 1996, recent reviews of health-care interventions were more likely to locate and include non-English-language studies and grey literature or unpublished studies, and to test for publication bias. Conclusions Dissemination of research findings is likely to be a biased process, although the actual impact of such bias depends on specific circumstances. The prospective registration of clinical trials and the endorsement of reporting guidelines may reduce research dissemination bias in clinical research. In systematic reviews, measures can be taken to minimise the impact of dissemination bias by systematically searching for and including relevant studies that are difficult to access. Statistical methods can be useful for sensitivity analyses. Further research is needed to develop methods for qualitatively assessing the risk of publication bias in systematic reviews, and to evaluate the effect of prospective registration of studies, open access policy and improved publication guidelines.

Prevention of childhood obesity is an international public health priority given the significant impact of obesity on acute and chronic diseases, general health, development and well-being. The international evidence base for strategies to prevent obesity is very large and is accumulating rapidly. This is an update of a previous review. To determine the effectiveness of a range of interventions that include diet or physical activity components, or both, designed to prevent obesity in children. We searched CENTRAL, MEDLINE, Embase, PsychINFO and CINAHL in June 2015. We re-ran the search from June 2015 to January 2018 and included a search of trial registers. Randomised controlled trials (RCTs) of diet or physical activity interventions, or combined diet and physical activity interventions, for preventing overweight or obesity in children (0-17 years) that reported outcomes at a minimum of 12 weeks from baseline. Two authors independently extracted data, assessed risk-of-bias and evaluated overall certainty of the evidence using GRADE. We extracted data on adiposity outcomes, sociodemographic characteristics, adverse events, intervention process and costs. We meta-analysed data as guided by the Cochrane Handbook for Systematic Reviews of Interventions and presented separate meta-analyses by age group for child 0 to 5 years, 6 to 12 years, and 13 to 18 years for zBMI and BMI. We included 153 RCTs, mostly from the USA or Europe. Thirteen studies were based in upper-middle-income countries (UMIC: Brazil, Ecuador, Lebanon, Mexico, Thailand, Turkey, US-Mexico border), and one was based in a lower middle-income country (LMIC: Egypt). The majority (85) targeted children aged 6 to 12 years.Children aged 0-5 years: There is moderate-certainty evidence from 16 RCTs (n = 6261) that diet combined with physical activity interventions, compared with control, reduced BMI (mean difference (MD) -0.07 kg/m2, 95% confidence interval (CI) -0.14 to -0.01), and had a similar effect (11 RCTs, n = 5536) on zBMI (MD -0.11, 95% CI -0.21 to 0.01). Neither diet (moderate-certainty evidence) nor physical activity interventions alone (high-certainty evidence) compared with control reduced BMI (physical activity alone: MD -0.22 kg/m2, 95% CI -0.44 to 0.01) or zBMI (diet alone: MD -0.14, 95% CI -0.32 to 0.04; physical activity alone: MD 0.01, 95% CI -0.10 to 0.13) in children aged 0-5 years.Children aged 6 to 12 years: There is moderate-certainty evidence from 14 RCTs (n = 16,410) that physical activity interventions, compared with control, reduced BMI (MD -0.10 kg/m2, 95% CI -0.14 to -0.05). However, there is moderate-certainty evidence that they had little or no effect on zBMI (MD -0.02, 95% CI -0.06 to 0.02). There is low-certainty evidence from 20 RCTs (n = 24,043) that diet combined with physical activity interventions, compared with control, reduced zBMI (MD -0.05 kg/m2, 95% CI -0.10 to -0.01). There is high-certainty evidence that diet interventions, compared with control, had little impact on zBMI (MD -0.03, 95% CI -0.06 to 0.01) or BMI (-0.02 kg/m2, 95% CI -0.11 to 0.06).Children aged 13 to 18 years: There is very low-certainty evidence that physical activity interventions, compared with control reduced BMI (MD -1.53 kg/m2, 95% CI -2.67 to -0.39; 4 RCTs; n = 720); and low-certainty evidence for a reduction in zBMI (MD -0.2, 95% CI -0.3 to -0.1; 1 RCT; n = 100). There is low-certainty evidence from eight RCTs (n = 16,583) that diet combined with physical activity interventions, compared with control, had no effect on BMI (MD -0.02 kg/m2, 95% CI -0.10 to 0.05); or zBMI (MD 0.01, 95% CI -0.05 to 0.07; 6 RCTs; n = 16,543). Evidence from two RCTs (low-certainty evidence; n = 294) found no effect of diet interventions on BMI.Direct comparisons of interventions: Two RCTs reported data directly comparing diet with either physical activity or diet combined with physical activity interventions for children aged 6 to 12 years and reported no differences.Heterogeneity was apparent in the results from all three age groups, which could not be entirely explained by setting or duration of the interventions. Where reported, interventions did not appear to result in adverse effects (16 RCTs) or increase health inequalities (gender: 30 RCTs; socioeconomic status: 18 RCTs), although relatively few studies examined these factors.Re-running the searches in January 2018 identified 315 records with potential relevance to this review, which will be synthesised in the next update. Interventions that include diet combined with physical activity interventions can reduce the risk of obesity (zBMI and BMI) in young children aged 0 to 5 years. There is weaker evidence from a single study that dietary interventions may be beneficial.However, interventions that focus only on physical activity do not appear to be effective in children of this age. In contrast, interventions that only focus on physical activity can reduce the risk of obesity (BMI) in children aged 6 to 12 years, and adolescents aged 13 to 18 years. In these age groups, there is no evidence that interventions that only focus on diet are effective, and some evidence that diet combined with physical activity interventions may be effective. Importantly, this updated review also suggests that interventions to prevent childhood obesity do not appear to result in adverse effects or health inequalities.The review will not be updated in its current form. To manage the growth in RCTs of child obesity prevention interventions, in future, this review will be split into three separate reviews based on child age.

Background: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD).