Treatments for dry age-related macular degeneration and Stargardt disease : a systematic review

Background Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. Objective To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Design Systematic review. Methods We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. Results The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or government

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

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

Parent-only interventions for childhood overweight or obesity in children aged 5 to 11 years

Background: Child and adolescent overweight and obesity have increased globally, and are associated with short- and long-term health consequences.Objectives: To assess the efficacy of diet, physical activity and behavioural interventions delivered to parents only for the treatment of overweight and obesity in children aged 5 to 11 years.Search methods: We performed a systematic literature search of databases including the Cochrane Library,MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS as well trial registers.We 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 delivered to parents only for treating overweight or obesity in children aged 5 to 11 years.Data collection and analysis: Two review authors independently assessed trials for risk of bias and evaluated overall study quality using the GRADE instrument. Where necessary, we contacted authors for additional information.Main results: We included 20 RCTs, including 3057 participants. The number of participants ranged per trial between 15 and 645. Follow-up ranged between 24 weeks and two years. Eighteen trials were parallel RCTs and two were cluster RCTs. Twelve RCTs had two comparisons and eight RCTs had three comparisons. The interventions varied widely; the duration, content, delivery and follow-up of the interventions were heterogeneous. The comparators also differed. This review categorised the comparisons into four groups: parent-only versus parent-child, parent-only versus waiting list controls, parent-only versus minimal contact interventions and parent-only versus other parent-only interventions. Trial quality was generally low with a large proportion of trials rated as high risk of bias on individual risk of bias criteria. In trials comparing a parent-only intervention with a parent-child intervention, the body mass index (BMI) z score change showed a mean difference (MD) at the longest follow-up period (10 to 24 months) of -0.04 (95% confidence interval (CI) -0.15 to 0.08); P = 0.56; 267 participants; 3 trials; low quality evidence. In trials comparing a parent-only intervention with a waiting list control, the BMI z score change in favour of the parent-only intervention at the longest follow-up period (10-12 months) had an MD of -0.10 (95% CI -0.19 to -0.01); P = 0.04; 136 participants; 2 trials; low quality evidence. BMI z score change of parent-only interventions when compared with minimal contact control interventions at the longest follow-up period (9 to 12 months) showed an MD of 0.01 (95% CI -0.07 to 0.09); P = 0.81; 165 participants; 1 trial; low quality evidence. There were few similarities between interventions and comparators across the included trials in the parent-only intervention versus other parent-only interventions and we did not pool these data. Generally, these trials did not show substantial differences between their respective parent-only groups on BMI outcomes. Other outcomes such as behavioural measures, parent-child relationships and health-related quality of life were reported inconsistently. Adverse effects of the interventions were generally not reported, two trials stated that there were no serious adverse effects. No trials reported on all-cause mortality, morbidity or socioeconomic effects. All results need to be interpreted cautiously because of their low quality, the heterogeneous interventions and comparators, and the high rates of non-completion.Authors’ conclusions: Parent-only interventions may be an effective treatment option for overweight or obese children aged 5 to 11 years when compared with waiting list controls. Parent-only interventions had similar effects compared with parent-child interventions and compared with those with minimal contact controls. However, the evidence is at present limited; some of the trials had a high risk of bias with loss to follow-up being a particular issue and there was a lack of evidence for several important outcomes. The systematic review has identified 10 ongoing trials that have a parent-only arm, which will contribute to future updates. These trials will improve the robustness of the analyses by type of comparator, and may permit subgroup analysis by intervention component and the setting. Trial reports should provide adequate details about the interventions to be replicated by others. There is a need to conduct and report cost effectiveness analyses in future trials in order to establish whether parent-only interventions are more cost-effective than parent-child interventions

The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

Background: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF. Methods: Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken. Results: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective. Conclusions: Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered

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

Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction : systematic review and economic evaluation

Background The blockage of a coronary artery (coronary thrombosis) can lead to a heart attack (acute myocardial infarction). There are several ways of trying to overcome this blockage. The methods include drug treatment to dissolve the clot (thrombolysis) and physical intervention, either by passing a catheter into the affected artery [angioplasty or percutaneous coronary intervention (PCI)], or bypassing the blocked section by cardiac surgery [coronary artery bypass grafting (CABG)]. Thrombolysis can be given in the community before the patient is sent to hospital, or delayed until after admission. Prehospital thrombolysis is not common in the UK. Immediate angioplasty is not routinely available in the UK at present; it is much more common in the USA. Objectives To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. Methods This report was based on a systematic review of the evidence of clinical effectiveness and an economic analysis of cost-effectiveness based on the clinical review and on cost data from published sources and de novo data collection. Data sources The search strategy searched six electronic databases (including Medline, Cochrane Library and EMBASE), with English-language limits, for the periods up to December 2002. Bibliographies of related papers were assessed for relevant studies and experts contacted for advice and peer review, and to identify additional published and unpublished references. Study selection For clinical effectiveness, a comprehensive review of randomised controlled trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data for effectiveness safety in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. They were used to assess the implications of wider diffusion of the technology away from major centres. Data extraction Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of systematic reviews, RCTs, controlled clinical trials and economic studies was assessed using criteria recommended by the NHS Centre for Reviews and Dissemination (University of York). Study synthesis Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). Results and conclusion Number and quality of studies, and summary of benefits There were several good-quality systematic reviews, including a Cochrane review, as well as an individual patient meta-analysis and a number of recent trials not included in the reviews. The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with PCI, with the difference being due to haemorrhagic stroke. The need for CABG is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. One good quality study from France showed that prehospital thrombolysis with PCI in those in whom thrombolysis failed was as good as universal PCI. Research on thrombolysis followed by PCI, known as facilitated PCI, is underway, but results are not yet available. Further caveats are needed. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than 1 hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Cost-effectiveness If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost and an incremental cost per unit change in health status under the £30,000 threshold in most instances. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. The model is not particularly sensitive to variations in probabilities from the clinical effectiveness analysis. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, could be used. In rural areas, one option could be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. Need for further research There is a need for economic data on the long-term consequences of the treatment, the quality of life of patients after treatment and the effects of PCI following thrombolysis failure

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

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. To assess the effects of diet, physical activity and behavioural interventions for the treatment of overweight or obese adolescents aged 12 to 17 years. 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. 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. 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. 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/m(2) (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/m(2) (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. 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

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