The potential impact of policies and structural interventions in reducing cardiovascular disease and mortality: a systematic review of simulation-based studies.

Background: The aim of the study was to investigate the potential effect of different structural interventions for preventing cardiovascular disease. Methods: Medline and EMBASE were searched for peer-reviewed simulation-based studies of structural interventions for prevention of cardiovascular disease. We performed a systematic narrative synthesis. Results: A total of 54 studies met the inclusion criteria. Diet, nutrition, tobacco and alcohol control and other programmes are among the policy simulation models explored. Food tax and subsidies, healthy food and lifestyles policies, palm oil tax, processed meat tax, reduction in ultra-processed foods, supplementary nutrition assistance programmes, stricter food policy and subsidised community-supported agriculture were among the diet and nutrition initiatives. Initiatives to reduce tobacco and alcohol use included a smoking ban, a national tobacco control initiative and a tax on alcohol. Others included the NHS Health Check, WHO 25 × 25 and air quality management policy. Future work and limitations: There is significant heterogeneity in simulation models, making comparisons of output data impossible. While policy interventions typically include a variety of strategies, none of the models considered possible interrelationships between multiple policies or potential interactions. Research that investigates dose-response interactions between numerous modifications as well as longer-term clinical outcomes can help us better understand the potential impact of policy-level interventions. Conclusions: The reviewed studies underscore the potential of structural interventions in addressing cardiovascular diseases. Notably, interventions in areas such as diet, tobacco, and alcohol control demonstrate a prospective decrease in cardiovascular incidents. However, to realize the full potential of such interventions, there is a pressing need for models that consider the interplay and cumulative impacts of multiple policies. Rigorous research into holistic and interconnected interventions will pave the way for more effective policy strategies in the future. Study registration: The study is registered as PROSPERO CRD42019154836. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/148/05.

This study aimed to explore the potential effects of various policy changes on the prevention of heart disease. By searching two large medical databases, we identified studies that employed computer models to estimate the impact of these policies on heart disease rates. In total, 54 studies matched our criteria. These studies considered a diverse range of policy interventions. Some delved into food and nutrition, investigating aspects like unhealthy food taxes, healthy food subsidies, stricter food regulations, and nutritional assistance programs. Others examined the impact of policies targeting tobacco and alcohol, encompassing smoking bans, nationwide tobacco control measures, and alcohol taxation. Further policies assessed included routine health checkups, global health goals, and measures to enhance air quality. One significant challenge lies in the varied approaches and models each study employed, making direct comparisons difficult. Furthermore, there's a gap in understanding how these policies might influence one another, as the studies did not consider potential interactions between them. While these policies show promise in the computer models, more comprehensive research is needed to fully appreciate their combined and long-term effects on heart health in real-world scenarios. As of now, we recognize the potential of these interventions, but further studies will determine their true impact on reducing heart disease rates.

Investigating informed choice in screening programmes: a mixed methods analysis.

BACKGROUND: Screening programmes aim to identify individuals at higher risk of developing a disease or condition. While globally, there is agreement that people who attend screening should be fully informed, there is no consensus about how this should be achieved. We conducted a mixed methods study across eight different countries to understand how countries address informed choice across two screening programmes: breast cancer and fetal trisomy anomaly screening. METHODS: Fourteen senior level employees from organisations who produce and deliver decision aids to assist informed choice were interviewed, and their decision aids (n = 15) were evaluated using documentary analysis. RESULTS: We discovered that attempts to achieve informed choice via decision aids generate two key tensions (i) between improving informed choice and increasing uptake and (ii) between improving informed choice and comprehensibility of the information presented. Comprehensibility is fundamentally at tension with an aim of being fully informed. These tensions emerged in both the interviews and documentary analysis. CONCLUSION: We conclude that organisations need to decide whether their overarching aim is ensuring high levels of uptake or maximising informed choice to participate in screening programmes. Consideration must then be given to all levels of development and distribution of information produced to reflect each organisation's aim. The comprehensibility of the DA must also be considered, as this may be reduced when informed choice is prioritised.

Increasing comprehensiveness and reducing workload in a systematic review of complex interventions using automated machine learning.

BACKGROUND: As part of our ongoing systematic review of complex interventions for the primary prevention of cardiovascular diseases, we have developed and evaluated automated machine-learning classifiers for title and abstract screening. The aim was to develop a high-performing algorithm comparable to human screening. METHODS: We followed a three-phase process to develop and test an automated machine learning-based classifier for screening potential studies on interventions for primary prevention of cardiovascular disease. We labelled a total of 16,611 articles during the first phase of the project. In the second phase, we used the labelled articles to develop a machine learning-based classifier. After that, we examined the performance of the classifiers in correctly labelling the papers. We evaluated the performance of the five deep-learning models [i.e. parallel convolutional neural network ( CNN ), stacked CNN , parallel-stacked CNN , recurrent neural network ( RNN ) and CNN-RNN]. The models were evaluated using recall, precision and work saved over sampling at no less than 95% recall. RESULTS: We labelled a total of 16,611 articles, of which 676 (4.0%) were tagged as 'relevant' and 15,935 (96%) were tagged as 'irrelevant'. The recall ranged from 51.9% to 96.6%. The precision ranged from 64.6% to 99.1%. The work saved over sampling ranged from 8.9% to as high as 92.1%. The best-performing model was parallel CNN , yielding a 96.4% recall, as well as 99.1% precision, and a potential workload reduction of 89.9%. FUTURE WORK AND LIMITATIONS: We used words from the title and the abstract only. More work needs to be done to look into possible changes in performance, such as adding features such as full document text. The approach might also not be able to be used for other complex systematic reviews on different topics. CONCLUSION: Our study shows that machine learning has the potential to significantly aid the labour-intensive screening of abstracts in systematic reviews of complex interventions. Future research should concentrate on enhancing the classifier system and determining how it can be integrated into the systematic review workflow. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in Health Technology Assessment. See the NIHR Journals Library website for further project information.

Factors associated with attendance at screening for breast cancer: a systematic review and meta-analysis.

OBJECTIVE: Attendance at population-based breast cancer (mammographic) screening varies. This comprehensive systematic review and meta-analysis assesses all identified patient-level factors associated with routine population breast screening attendance. DESIGN: CINAHL, Cochrane Library, Embase, Medline, OVID, PsycINFO and Web of Science were searched for studies of any design, published January 1987-June 2019, and reporting attendance in relation to at least one patient-level factor. DATA SYNTHESIS: Independent reviewers performed screening, data extraction and quality appraisal. OR and 95% CIs were calculated for attendance for each factor and random-effects meta-analysis was undertaken where possible. RESULTS: Of 19 776 studies, 335 were assessed at full text and 66 studies (n=22 150 922) were included. Risk of bias was generally low. In meta-analysis, increased attendance was associated with higher socioeconomic status (SES) (n=11 studies; OR 1.45, 95% CI: 1.20 to 1.75); higher income (n=5 studies; OR 1.96, 95% CI: 1.68 to 2.29); home ownership (n=3 studies; OR 2.16, 95% CI: 2.08 to 2.23); being non-immigrant (n=7 studies; OR 2.23, 95% CI: 2.00 to 2.48); being married/cohabiting (n=7 studies; OR 1.86, 95% CI: 1.58 to 2.19) and medium (vs low) level of education (n=6 studies; OR 1.24, 95% CI: 1.09 to 1.41). Women with previous false-positive results were less likely to reattend (n=6 studies; OR 0.77, 95% CI: 0.68 to 0.88). There were no differences by age group or by rural versus urban residence. CONCLUSIONS: Attendance was lower in women with lower SES, those who were immigrants, non-homeowners and those with previous false-positive results. Variations in service delivery, screening programmes and study populations may influence findings. Our findings are of univariable associations. Underlying causes of lower uptake such as practical, physical, psychological or financial barriers should be investigated. TRIAL REGISTRATION NUMBER: CRD42016051597.

The Double Burden of Malnutrition and Associated Factors among South Asian Adolescents: Findings from the Global School-Based Student Health Survey.

The health and nutrition of the global adolescent population have been under-researched, in spite of its significant size (1.2 billion). This study investigates the prevalence and associated factors of malnutrition (stunting, thinness and overweight) among adolescents living in South Asia. The sample analysed was 24,053 South Asian schooled adolescents aged 12-15 years that participated in the cross-sectional Global School-Based Student Health Survey (GSHS) between 2009 and 2016. The prevalence of stunting, thinness and overweight was calculated using the World Health Organization (WHO) Child Growth Reference 2007. Associations between the three forms of malnutrition and their possible associated factors were assessed with binary logistic regression analysis using bootstrapping as a resampling method. The overall prevalence of stunting in South Asia was 13%, thinness was 10.8% and overweight was 10.8%. In the logistic regression model of the overall pooled sample, the factors associated with adolescent malnutrition were: age, hygiene behaviours, social support, sedentary behaviour, and tobacco use. A substantial proportion of stunting, thinness and overweight was found among school-going South Asian adolescents, indicating that the double burden of malnutrition is present in this population. Future research should seek to further understand the relationship between all forms of malnutrition and its associated factors in the adolescent population.

Testing strategies for Lynch syndrome in people with endometrial cancer: systematic reviews and economic evaluation.

BACKGROUND: Lynch syndrome is an inherited genetic condition that is associated with an increased risk of certain cancers. The National Institute for Health and Care Excellence has recommended that people with colorectal cancer are tested for Lynch syndrome. Routine testing for Lynch syndrome among people with endometrial cancer is not currently conducted. OBJECTIVES: To systematically review the evidence on the test accuracy of immunohistochemistry- and microsatellite instability-based strategies to detect Lynch syndrome among people who have endometrial cancer, and the clinical effectiveness and the cost-effectiveness of testing for Lynch syndrome among people who have been diagnosed with endometrial cancer. DATA SOURCES: Searches were conducted in the following databases, from inception to August 2019 - MEDLINE ALL, EMBASE (both via Ovid), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (both via Wiley Online Library), Database of Abstracts of Reviews of Effects, Health Technology Assessment Database (both via the Centre for Reviews and Dissemination), Science Citation Index, Conference Proceedings Citation Index - Science (both via Web of Science), PROSPERO international prospective register of systematic reviews (via the Centre for Reviews and Dissemination), NHS Economic Evaluation Database, Cost-Effectiveness Analysis Registry, EconPapers (Research Papers in Economics) and School of Health and Related Research Health Utilities Database. The references of included studies and relevant systematic reviews were also checked and experts on the team were consulted. REVIEW METHODS: Eligible studies included people with endometrial cancer who were tested for Lynch syndrome using immunohistochemistry- and/or microsatellite instability-based testing [with or without mutL homologue 1 (MLH1) promoter hypermethylation testing], with Lynch syndrome diagnosis being established though germline testing of normal (non-tumour) tissue for constitutional mutations in mismatch repair. The risk of bias in studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, the Consolidated Health Economic Reporting Standards and the Philips' checklist. Two reviewers independently conducted each stage of the review. A meta-analysis of test accuracy was not possible because of the number and heterogeneity of studies. A narrative summary of test accuracy results was provided, reporting test accuracy estimates and presenting forest plots. The economic model constituted a decision tree followed by Markov models for the impact of colorectal and endometrial surveillance, and aspirin prophylaxis with a lifetime time horizon. RESULTS: The clinical effectiveness search identified 3308 studies; 38 studies of test accuracy were included. (No studies of clinical effectiveness of endometrial cancer surveillance met the inclusion criteria.) Four test accuracy studies compared microsatellite instability with immunohistochemistry. No clear difference in accuracy between immunohistochemistry and microsatellite instability was observed. There was some evidence that specificity of immunohistochemistry could be improved with the addition of methylation testing. There was high concordance between immunohistochemistry and microsatellite instability. The economic model indicated that all testing strategies, compared with no testing, were cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Immunohistochemistry with MLH1 promoter hypermethylation testing was the most cost-effective strategy, with an incremental cost-effectiveness ratio of £9420 per quality-adjusted life-year. The second most cost-effective strategy was immunohistochemistry testing alone, but incremental analysis produced an incremental cost-effectiveness ratio exceeding £130,000. Results were robust across all scenario analyses. Incremental cost-effectiveness ratios ranged from £5690 to £20,740; only removing the benefits of colorectal cancer surveillance produced an incremental cost-effectiveness ratio in excess of the £20,000 willingness-to-pay threshold. A sensitivity analysis identified the main cost drivers of the incremental cost-effectiveness ratio as percentage of relatives accepting counselling and prevalence of Lynch syndrome in the population. A probabilistic sensitivity analysis showed, at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year, a 0.93 probability that immunohistochemistry with MLH1 promoter hypermethylation testing is cost-effective, compared with no testing. LIMITATIONS: The systematic review excluded grey literature, studies written in non-English languages and studies for which the reference standard could not be established. Studies were included when Lynch syndrome was diagnosed by genetic confirmation of constitutional variants in the four mismatch repair genes (i.e. MLH1, mutS homologue 2, mutS homologue 6 and postmeiotic segregation increased 2). Variants of uncertain significance were reported as per the studies. There were limitations in the economic model around uncertainty in the model parameters and a lack of modelling of the potential harms of gynaecological surveillance and specific pathway modelling of genetic testing for somatic mismatch repair mutations. CONCLUSION: The economic model suggests that testing women with endometrial cancer for Lynch syndrome is cost-effective, but that results should be treated with caution because of uncertain model inputs. FUTURE WORK: Randomised controlled trials could provide evidence on the effect of earlier intervention on outcomes and the balance of benefits and harms of gynaecological cancer surveillance. Follow-up of negative cases through disease registers could be used to determine false negative cases. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019147185. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 42. See the NIHR Journals Library website for further project information.

Lynch syndrome is an inherited condition that is caused by a problem in the genes. People who have Lynch syndrome have a higher risk of some types of cancer (such as bowel and womb cancers) than people who do not have it. Identifying Lynch syndrome could stop cancers developing, lead to earlier treatment for cancers and help to find other family members who might have it. Currently, the National Institute for Health and Care Excellence guidance recommends testing for Lynch syndrome in people who have bowel cancer. Our aim was to investigate whether or not we should test for Lynch syndrome in women with womb cancer, and their relatives. We investigated two main tests: immunohistochemistry and microsatellite instability. There was no clear evidence that one of these tests is better than the other. There is some evidence that both tests are reasonably accurate. There was no good-quality evidence about whether or not treating women with Lynch syndrome with extra cancer screening and aspirin improves their outcomes. We used the best evidence available in our economic model, but it was at high risk of bias. The economic model suggested that testing women with endometrial cancer for Lynch syndrome is cost-effective. The best test in the model was immunohistochemistry followed by methylation testing. We are unsure of these results because of the low quality of evidence available.

Testing for lynch syndrome in people with endometrial cancer using immunohistochemistry and microsatellite instability-based testing strategies - A systematic review of test accuracy.

BACKGROUND: Lynch syndrome is an inherited genetic condition that is associated with an increased risk of cancer, including endometrial and colorectal cancer. We assessed the test accuracy of immunohistochemistry and microsatellite instability-based testing (with or without MLH1 promoter methylation testing) for Lynch syndrome in women with endometrial cancer. METHODS: We conducted a systematic review of literature published up to August 2019. We searched bibliographic databases, contacted experts and checked reference lists of relevant studies. Two reviewers conducted each stage of the review. RESULTS: Thirteen studies were identified that included approximately 3500 participants. None of the studies was at low risk of bias in all domains. Data could not be pooled due to the small number of heterogeneous studies. Sensitivity ranged from 60.7-100% for immunohistochemistry, 41.7-100% for microsatellite instability-based testing, and 90.5-100% for studies combining immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation testing. Specificity ranged from 60.9-83.3% (excluding 1 study with highly selective inclusion criteria) for immunohistochemistry, 69.2-89.9% for microsatellite instability-based testing, and 72.4-92.3% (excluding 1 study with highly selective inclusion criteria) for testing strategies that included immunohistochemistry, microsatellite instability-based testing, and MLH1 promoter methylation. We found no statistically significant differences in test accuracy estimates (sensitivity, specificity) in head-to-head studies of immunohistochemistry versus microsatellite instability-based testing. Reported test failures were rare. CONCLUSIONS: Sensitivity of the index tests were generally high, though most studies had much lower specificity. We found no evidence that test accuracy differed between IHC and MSI based strategies. The evidence base is currently small and at high risk of bias.

Determining optimal strategies for primary prevention of cardiovascular disease: systematic review, cost-effectiveness review and network meta-analysis protocol.

BACKGROUND: Despite recent improvements in the burden of cardiovascular disease (CVD) in the UK, deaths from CVD are relatively high compared with other high-income countries. An estimated 7 million people in the UK are living with CVD, and the healthcare cost is approximately £11 billion annually. In more than 90% of cases, the risk of a first heart attack is thought to be related to modifiable risk factors including smoking, poor diet, lipidemia, high blood pressure, inactivity, obesity and excess alcohol consumption. The aim of the study is to synthesise evidence for the comparative effectiveness and cost-effectiveness of different interventions for the primary prevention of CVD. METHODS: We will systematically search databases (for example, MEDLINE (Ovid), Embase (Ovid), Cochrane Library) and the reference lists of previous systematic reviews for randomised controlled trials that assess the effectiveness and cost-effectiveness of any form of intervention aimed at adult populations for the primary prevention of CVD, including but not limited to lipid lowering medications, blood pressure lowering medications, antiplatelet agents, nutritional supplements, dietary interventions, health promotion programmes, physical activity interventions or structural and policy interventions. Interventions may or may not be targeted at high-risk groups. Publications from any year will be considered for inclusion. The primary outcome will be all cause mortality. Secondary outcomes will be cardiovascular diseases related mortality, major cardiovascular events, coronary heart disease, incremental costs per quality-adjusted life years gained. If data permits, we will use network meta-analysis to compare and rank effectiveness of different interventions, and test effect modification of intervention effectiveness using subgroup analyses and meta-regression analyses. DISCUSSION: The results will be important for policymakers when making decisions between multiple possible alternative strategies to prevent CVD. Compared to results from existing multiple separate pairwise meta-analyses, this overarching synthesis of all relevant work will enhance decision-making. The findings will be crucial to inform evidence-based priorities and guidelines for policies and planning prevention strategies of CVD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019123940.

Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews.

Children and adolescents with overweight and obesity are a global health concern. This is an integrative overview of six Cochrane systematic reviews, providing an up-to-date synthesis of the evidence examining interventions for the treatment of children and adolescents with overweight or obesity. The data extraction and quality assessments for each review were conducted by one author and checked by a second. The six high quality reviews provide evidence on the effectiveness of behaviour changing interventions conducted in children <6 years (7 trials), 6-11 years (70 trials), adolescents 12-17 years (44 trials) and interventions that target only parents of children aged 5-11 years (20 trials); in addition to interventions examining surgery (1 trial) and drugs (21 trials). Most of the evidence was derived from high-income countries and published in the last two decades. Collectively, the evidence suggests that multi-component behaviour changing interventions may be beneficial in achieving small reductions in body weight status in children of all ages, with low adverse event occurrence were reported. More research is required to understand which specific intervention components are most effective and in whom, and how best to maintain intervention effects. Evidence from surgical and drug interventions was too limited to make inferences about use and safety, and adverse events were a serious consideration.

Whole grain cereals for the primary or secondary prevention of cardiovascular disease.

BACKGROUND: There is evidence from observational studies that whole grains can have a beneficial effect on risk for cardiovascular disease (CVD). Earlier versions of this review found mainly short-term intervention studies. There are now longer-term randomised controlled trials (RCTs) available. This is an update and expansion of the original review conducted in 2007. OBJECTIVES: The aim of this systematic review was to assess the effect of whole grain foods or diets on total mortality, cardiovascular events, and cardiovascular risk factors (blood lipids, blood pressure) in healthy people or people who have established cardiovascular disease or related risk factors, using all eligible RCTs. SEARCH METHODS: We searched CENTRAL (Issue 8, 2016) in the Cochrane Library, MEDLINE (1946 to 31 August 2016), Embase (1980 to week 35 2016), and CINAHL Plus (1937 to 31 August 2016) on 31 August 2016. We also searched ClinicalTrials.gov on 5 July 2017 and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) on 6 July 2017. We checked reference lists of relevant articles and applied no language restrictions. SELECTION CRITERIA: We selected RCTs assessing the effects of whole grain foods or diets containing whole grains compared to foods or diets with a similar composition, over a minimum of 12 weeks, on cardiovascular disease and related risk factors. Eligible for inclusion were healthy adults, those at increased risk of CVD, or those previously diagnosed with CVD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies. Data were extracted and quality-checked by one review author and checked by a second review author. A second review author checked the analyses. We assessed treatment effect using mean difference in a fixed-effect model and heterogeneity using the I2 statistic and the Chi2 test of heterogeneity. We assessed the overall quality of evidence using GRADE with GRADEpro software. MAIN RESULTS: We included nine RCTs randomising a total of 1414 participants (age range 24 to 70; mean age 45 to 59, where reported) to whole grain versus lower whole grain or refined grain control groups. We found no studies that reported the effect of whole grain diets on total cardiovascular mortality or cardiovascular events (total myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, total stroke). All included studies reported the effect of whole grain diets on risk factors for cardiovascular disease including blood lipids and blood pressure. All studies were in primary prevention populations and had an unclear or high risk of bias, and no studies had an intervention duration greater than 16 weeks.Overall, we found no difference between whole grain and control groups for total cholesterol (mean difference 0.07, 95% confidence interval -0.07 to 0.21; 6 studies (7 comparisons); 722 participants; low-quality evidence).Using GRADE, we assessed the overall quality of the available evidence on cholesterol as low. Four studies were funded by independent national and government funding bodies, while the remaining studies reported funding or partial funding by organisations with commercial interests in cereals. AUTHORS' CONCLUSIONS: There is insufficient evidence from RCTs of an effect of whole grain diets on cardiovascular outcomes or on major CVD risk factors such as blood lipids and blood pressure. Trials were at unclear or high risk of bias with small sample sizes and relatively short-term interventions, and the overall quality of the evidence was low. There is a need for well-designed, adequately powered RCTs with longer durations assessing cardiovascular events as well as cardiovascular risk factors.

Low glycaemic index diets for the prevention of cardiovascular disease.

BACKGROUND: The glycaemic index (GI) is a physiological measure of the ability of a carbohydrate to affect blood glucose. Interest is growing in this area for the clinical management of people at risk of, or with, established cardiovascular disease. There is a need to review the current evidence from randomised controlled trials (RCTs) in this area. This is an update of the original review published in 2008. OBJECTIVES: To assess the effect of the dietary GI on total mortality, cardiovascular events, and cardiovascular risk factors (blood lipids, blood pressure) in healthy people or people who have established cardiovascular disease or related risk factors, using all eligible randomised controlled trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL in July 2016. We also checked reference lists of relevant articles. No language restrictions were applied. SELECTION CRITERIA: We selected RCTs that assessed the effects of low GI diets compared to diets with a similar composition but a higher GI on cardiovascular disease and related risk factors. Minimum trial duration was 12 weeks. Participants included were healthy adults or those at increased risk of cardiovascular disease, or previously diagnosed with cardiovascular disease. Studies in people with diabetes mellitus were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened and selected studies. Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using GRADE, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. Analyses were checked by a second reviewer. Continuous outcomes were synthesized using mean differences and adverse events were synthesized narratively. MAIN RESULTS: Twenty-one RCTs were included, with a total of 2538 participants randomised to low GI intervention (1288) or high GI (1250). All 21 included studies reported the effect of low GI diets on risk factors for cardiovascular disease, including blood lipids and blood pressure.Twenty RCTs (18 of which were newly included in this version of the review) included primary prevention populations (healthy individuals or those at high risk of CVD, with mean age range from 19 to 69 years) and one RCT was in those diagnosed with pre-existing CVD (a secondary prevention population, with mean age 26.9 years). Most of the studies did not have an intervention duration of longer than six months. Difference in GI intake between comparison groups varied widely from 0.6 to 42.None of the included studies reported the effect of low GI dietary intake on cardiovascular mortality and cardiovascular events such as fatal and nonfatal myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, and stroke. The unclear risk of bias of most of the included studies makes overall interpretation of the data difficult. Only two of the included studies (38 participants) reported on adverse effects and did not observe any harms (low-quality evidence). AUTHORS' CONCLUSIONS: There is currently no evidence available regarding the effect of low GI diets on cardiovascular disease events. Moreover, there is currently no convincing evidence that low GI diets have a clear beneficial effect on blood lipids or blood pressure parameters.

Diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years.

BACKGROUND: Adolescent overweight and obesity has increased globally, and can be associated with short- and long-term health consequences. Modifying known dietary and behavioural risk factors through behaviour changing interventions (BCI) may help to reduce childhood overweight and obesity. This is an update of a review published in 2009. OBJECTIVES: To assess the effects of diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years. SEARCH METHODS: We performed a systematic literature search in: CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, and the trial registers ClinicalTrials.gov and ICTRP Search Portal. We checked references of identified studies and systematic reviews. There were no language restrictions. The date of the last search was July 2016 for all databases. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of diet, physical activity and behavioural interventions for treating overweight or obesity in adolescents aged 12 to 17 years. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument and extracted data following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. MAIN RESULTS: We included 44 completed RCTs (4781 participants) and 50 ongoing studies. The number of participants in each trial varied (10 to 521) as did the length of follow-up (6 to 24 months). Participants ages ranged from 12 to 17.5 years in all trials that reported mean age at baseline. Most of the trials used a multidisciplinary intervention with a combination of diet, physical activity and behavioural components. The content and duration of the intervention, its delivery and the comparators varied across trials. The studies contributing most information to outcomes of weight and body mass index (BMI) were from studies at a low risk of bias, but studies with a high risk of bias provided data on adverse events and quality of life.The mean difference (MD) of the change in BMI at the longest follow-up period in favour of BCI was -1.18 kg/m2 (95% confidence interval (CI) -1.67 to -0.69); 2774 participants; 28 trials; low quality evidence. BCI lowered the change in BMI z score by -0.13 units (95% CI -0.21 to -0.05); 2399 participants; 20 trials; low quality evidence. BCI lowered body weight by -3.67 kg (95% CI -5.21 to -2.13); 1993 participants; 20 trials; moderate quality evidence. The effect on weight measures persisted in trials with 18 to 24 months' follow-up for both BMI (MD -1.49 kg/m2 (95% CI -2.56 to -0.41); 760 participants; 6 trials and BMI z score MD -0.34 (95% CI -0.66 to -0.02); 602 participants; 5 trials).There were subgroup differences showing larger effects for both BMI and BMI z score in studies comparing interventions with no intervention/wait list control or usual care, compared with those testing concomitant interventions delivered to both the intervention and control group. There were no subgroup differences between interventions with and without parental involvement or by intervention type or setting (health care, community, school) or mode of delivery (individual versus group).The rate of adverse events in intervention and control groups was unclear with only five trials reporting harms, and of these, details were provided in only one (low quality evidence). None of the included studies reported on all-cause mortality, morbidity or socioeconomic effects.BCIs at the longest follow-up moderately improved adolescent's health-related quality of life (standardised mean difference 0.44 ((95% CI 0.09 to 0.79); P = 0.01; 972 participants; 7 trials; 8 comparisons; low quality of evidence) but not self-esteem.Trials were inconsistent in how they measured dietary intake, dietary behaviours, physical activity and behaviour. AUTHORS' CONCLUSIONS: We found low quality evidence that multidisciplinary interventions involving a combination of diet, physical activity and behavioural components reduce measures of BMI and moderate quality evidence that they reduce weight in overweight or obese adolescents, mainly when compared with no treatment or waiting list controls. Inconsistent results, risk of bias or indirectness of outcome measures used mean that the evidence should be interpreted with caution. We have identified a large number of ongoing trials (50) which we will include in future updates of this review.

Diet, physical activity and behavioural interventions for the treatment of overweight or obese children from the age of 6 to 11 years.

BACKGROUND: Child and adolescent overweight and obesity has increased globally, and can be associated with significant short- and long-term health consequences. This is an update of a Cochrane review published first in 2003, and updated previously in 2009. However, the update has now been split into six reviews addressing different childhood obesity treatments at different ages. OBJECTIVES: To assess the effects of diet, physical activity and behavioural interventions (behaviour-changing interventions) for the treatment of overweight or obese children aged 6 to 11 years. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS as well as trial registers ClinicalTrials.gov and ICTRP Search Portal. We checked references of studies and systematic reviews. We did not apply any language restrictions. The date of the last search was July 2016 for all databases. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions (behaviour-changing interventions) for treating overweight or obese children aged 6 to 11 years, with a minimum of six months' follow-up. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references, extracted data, assessed risk of bias, and evaluated the quality of the evidence using the GRADE instrument. We contacted study authors for additional information. We carried out meta-analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included 70 RCTs with a total of 8461 participants randomised to either the intervention or control groups. The number of participants per trial ranged from 16 to 686. Fifty-five trials compared a behaviour-changing intervention with no treatment/usual care control and 15 evaluated the effectiveness of adding an additional component to a behaviour-changing intervention. Sixty-four trials were parallel RCTs, and four were cluster RCTs. Sixty-four trials were multicomponent, two were diet only and four were physical activity only interventions. Ten trials had more than two arms. The overall quality of the evidence was low or very low and 62 trials had a high risk of bias for at least one criterion. Total duration of trials ranged from six months to three years. The median age of participants was 10 years old and the median BMI z score was 2.2.Primary analyses demonstrated that behaviour-changing interventions compared to no treatment/usual care control at longest follow-up reduced BMI, BMI z score and weight. Mean difference (MD) in BMI was -0.53 kg/m2 (95% confidence interval (CI) -0.82 to -0.24); P < 0.00001; 24 trials; 2785 participants; low-quality evidence. MD in BMI z score was -0.06 units (95% CI -0.10 to -0.02); P = 0.001; 37 trials; 4019 participants; low-quality evidence and MD in weight was -1.45 kg (95% CI -1.88 to -1.02); P < 0.00001; 17 trials; 1774 participants; low-quality evidence.Thirty-one trials reported on serious adverse events, with 29 trials reporting zero occurrences RR 0.57 (95% CI 0.17 to 1.93); P = 0.37; 4/2105 participants in the behaviour-changing intervention groups compared with 7/1991 participants in the comparator groups). Few trials reported health-related quality of life or behaviour change outcomes, and none of the analyses demonstrated a substantial difference in these outcomes between intervention and control. In two trials reporting on minutes per day of TV viewing, a small reduction of 6.6 minutes per day (95% CI -12.88 to -0.31), P = 0.04; 2 trials; 55 participants) was found in favour of the intervention. No trials reported on all-cause mortality, morbidity or socioeconomic effects, and few trials reported on participant views; none of which could be meta-analysed.As the meta-analyses revealed substantial heterogeneity, we conducted subgroup analyses to examine the impact of type of comparator, type of intervention, risk of attrition bias, setting, duration of post-intervention follow-up period, parental involvement and baseline BMI z score. No subgroup effects were shown for any of the subgroups on any of the outcomes. Some data indicated that a reduction in BMI immediately post-intervention was no longer evident at follow-up at less than six months, which has to be investigated in further trials. AUTHORS' CONCLUSIONS: Multi-component behaviour-changing interventions that incorporate diet, physical activity and behaviour change may be beneficial in achieving small, short-term reductions in BMI, BMI z score and weight in children aged 6 to 11 years. The evidence suggests a very low occurrence of adverse events. The quality of the evidence was low or very low. The heterogeneity observed across all outcomes was not explained by subgrouping. Further research is required of behaviour-changing interventions in lower income countries and in children from different ethnic groups; also on the impact of behaviour-changing interventions on health-related quality of life and comorbidities. The sustainability of reduction in BMI/BMI z score and weight is a key consideration and there is a need for longer-term follow-up and further research on the most appropriate forms of post-intervention maintenance in order to ensure intervention benefits are sustained over the longer term.

Vitamin C supplementation for the primary prevention of cardiovascular disease.

BACKGROUND: Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent. OBJECTIVES: To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD. SEARCH METHODS: We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias. MAIN RESULTS: We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding. AUTHORS' CONCLUSIONS: Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

Diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years.

BACKGROUND: Child overweight and obesity has increased globally, and can be associated with short- and long-term health consequences. OBJECTIVES: To assess the effects of diet, physical activity, and behavioural interventions for the treatment of overweight or obesity in preschool children up to the age of 6 years. SEARCH METHODS: We performed a systematic literature search in the databases Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, and LILACS, as well as in the trial registers ClinicalTrials.gov and ICTRP Search Portal. We also checked references of identified trials and systematic reviews. We applied no language restrictions. The date of the last search was March 2015 for all databases. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of diet, physical activity, and behavioural interventions for treating overweight or obesity in preschool children aged 0 to 6 years. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using the GRADE instrument, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. MAIN RESULTS: We included 7 RCTs with a total of 923 participants: 529 randomised to an intervention and 394 to a comparator. The number of participants per trial ranged from 18 to 475. Six trials were parallel RCTs, and one was a cluster RCT. Two trials were three-arm trials, each comparing two interventions with a control group. The interventions and comparators in the trials varied. We categorised the comparisons into two groups: multicomponent interventions and dietary interventions. The overall quality of the evidence was low or very low, and six trials had a high risk of bias on individual 'Risk of bias' criteria. The children in the included trials were followed up for between six months and three years.In trials comparing a multicomponent intervention with usual care, enhanced usual care, or information control, we found a greater reduction in body mass index (BMI) z score in the intervention groups at the end of the intervention (6 to 12 months): mean difference (MD) -0.3 units (95% confidence interval (CI) -0.4 to -0.2); P < 0.00001; 210 participants; 4 trials; low-quality evidence, at 12 to 18 months' follow-up: MD -0.4 units (95% CI -0.6 to -0.2); P = 0.0001; 202 participants; 4 trials; low-quality evidence, and at 2 years' follow-up: MD -0.3 units (95% CI -0.4 to -0.1); 96 participants; 1 trial; low-quality evidence.One trial stated that no adverse events were reported; the other trials did not report on adverse events. Three trials reported health-related quality of life and found improvements in some, but not all, aspects. Other outcomes, such as behaviour change and parent-child relationship, were inconsistently measured.One three-arm trial of very low-quality evidence comparing two types of diet with control found that both the dairy-rich diet (BMI z score change MD -0.1 units (95% CI -0.11 to -0.09); P < 0.0001; 59 participants) and energy-restricted diet (BMI z score change MD -0.1 units (95% CI -0.11 to -0.09); P < 0.0001; 57 participants) resulted in greater reduction in BMI than the comparator at the end of the intervention period, but only the dairy-rich diet maintained this at 36 months' follow-up (BMI z score change in MD -0.7 units (95% CI -0.71 to -0.69); P < 0.0001; 52 participants). The energy-restricted diet had a worse BMI outcome than control at this follow-up (BMI z score change MD 0.1 units (95% CI 0.09 to 0.11); P < 0.0001; 47 participants). There was no substantial difference in mean daily energy expenditure between groups. Health-related quality of life, adverse effects, participant views, and parenting were not measured.No trial reported on all-cause mortality, morbidity, or socioeconomic effects.All results should be interpreted cautiously due to their low quality and heterogeneous interventions and comparators. AUTHORS' CONCLUSIONS: Muticomponent interventions appear to be an effective treatment option for overweight or obese preschool children up to the age of 6 years. However, the current evidence is limited, and most trials had a high risk of bias. Most trials did not measure adverse events. We have identified four ongoing trials that we will include in future updates of this review.The role of dietary interventions is more equivocal, with one trial suggesting that dairy interventions may be effective in the longer term, but not energy-restricted diets. This trial also had a high risk of bias.