Diane Threapleton

Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis

Objective To investigate dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease. Design Systematic review of available literature and dose-response meta-analysis of cohort studies using random effects models. Data sources The Cochrane Library, Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS, and hand searching. Eligibility criteria for studies Prospective studies reporting associations between fibre intake and coronary heart disease or cardiovascular disease, with a minimum follow-up of three years and published in English between 1 January 1990 and 6 August 2013. Results 22 cohort study publications met inclusion criteria and reported total dietary fibre intake, fibre subtypes, or fibre from food sources and primary events of cardiovascular disease or coronary heart disease. Total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95% confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to 0.94)). There was evidence of some heterogeneity between pooled studies for cardiovascular disease (I2=45% (0% to 74%)) and coronary heart disease (I2=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease. Conclusions Greater dietary fibre intake is associated with a lower risk of both cardiovascular disease and coronary heart disease. Findings are aligned with general recommendations to increase fibre intake. The differing strengths of association by fibre type or source highlight the need for a better understanding of the mode of action of fibre components.

Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose–response meta-analysis of prospective studies

The intake of sugar-sweetened soft drinks has been reported to be associated with an increased risk of type 2 diabetes, but it is unclear whether this is because of the sugar content or related lifestyle factors, whether similar associations hold for artificially sweetened soft drinks, and how these associations are related to BMI. We aimed to conduct a systematic literature review and dose-response meta-analysis of evidence from prospective cohorts to explore these issues. We searched multiple sources for prospective studies on sugar-sweetened and artificially sweetened soft drinks in relation to the risk of type 2 diabetes. Data were extracted from eleven publications on nine cohorts. Consumption values were converted to ml/d, permitting the exploration of linear and non-linear dose-response trends. Summary relative risks (RR) were estimated using a random-effects meta-analysis. The summary RR for sugar-sweetened and artificially sweetened soft drinks were 1·20/330 ml per d (95 % CI 1·12, 1·29, P< 0·001) and 1·13/330 ml per d (95 % CI 1·02, 1·25, P= 0·02), respectively. The association with sugar-sweetened soft drinks was slightly lower in studies adjusting for BMI, consistent with BMI being involved in the causal pathway. There was no evidence of effect modification, though both these comparisons lacked power. Overall between-study heterogeneity was high. The included studies were observational, so their results should be interpreted cautiously, but findings indicate a positive association between sugar-sweetened soft drink intake and type 2 diabetes risk, attenuated by adjustment for BMI. The trend was less consistent for artificially sweetened soft drinks. This may indicate an alternative explanation, such as lifestyle factors or reverse causality. Future research should focus on the temporal nature of the association and whether BMI modifies or mediates the association.

Glycemic Index, Glycemic Load, Carbohydrates, and Type 2 Diabetes: Systematic review and dose–response meta-analysis of prospective studies

OBJECTIVE Diets with high glycemic index (GI), with high glycemic load (GL), or high in all carbohydrates may predispose to higher blood glucose and insulin concentrations, glucose intolerance, and risk of type 2 diabetes. We aimed to conduct a systematic literature review and dose–response meta-analysis of evidence from prospective cohorts. RESEARCH DESIGN AND METHODS We searched the Cochrane Library, MEDLINE, MEDLINE in-process, Embase, CAB Abstracts, ISI Web of Science, and BIOSIS for prospective studies of GI, GL, and total carbohydrates in relation to risk of type 2 diabetes up to 17 July 2012. Data were extracted from 24 publications on 21 cohort studies. Studies using different exposure categories were combined on the same scale using linear and nonlinear dose–response trends. Summary relative risks (RRs) were estimated using random-effects meta-analysis. RESULTS The summary RR was 1.08 per 5 GI units (95% CI 1.02–1.15; P = 0.01), 1.03 per 20 GL units (95% CI 1.00–1.05; P = 0.02), and 0.97 per 50 g/day of carbohydrate (95% CI 0.90–1.06; P = 0.5). Dose–response trends were linear for GI and GL but more complex for total carbohydrate intake. Heterogeneity was high for all exposures (I2 >50%), partly accounted for by different covariate adjustment and length of follow-up. CONCLUSIONS Included studies were observational and should be interpreted cautiously. However, our findings are consistent with protective effects of low dietary GI and GL, quantifying the range of intakes associated with lower risk. Future research could focus on the type of sugars and other carbohydrates associated with greatest risk.

Dietary Fiber Intake and Risk of First Stroke: A Systematic Review and Meta-Analysis

Background and Purpose— Fiber intake is associated with reduced stroke risk in prospective studies, but no meta-analysis has been published to date. Methods— Multiple electronic databases were searched for healthy participant studies reporting fiber intake and incidence of first hemorrhagic or ischemic stroke, published between January 1990 and May 2012. Results— Eight cohort studies from the United States, northern Europe, Australia, and Japan met inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke, with some evidence of heterogeneity between studies (I2; relative risk per 7 g/day, 0.93; 95% confidence interval, 0.88–0.98; I2=59%). Soluble fiber intake, per 4 g/day, was not associated with stroke risk reduction with evidence of low heterogeneity between studies, relative risk 0.94 (95% confidence interval, 0.88–1.01; I2=21%). There were few studies reporting stroke risk in relation to insoluble fiber or fiber from cereals, fruit, or vegetables. Conclusions— Greater dietary fiber intake is significantly associated with lower risk of first stroke. Overall, findings support dietary recommendations to increase intake of total dietary fiber. However, a paucity of data on fiber from different foods precludes conclusions regarding the association between fiber type and stroke. There is a need for future studies to focus on fiber type and to examine risk for ischemic and hemorrhagic strokes separately.

Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis.

Objective To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens. Design Systematic review and network meta-analysis. Data sources Cochrane Library, PubMed, and Embase without language or date restrictions. Study selection Full text reports of randomised controlled trials that compared different eradication treatments for H pylori among adults. Results Of the 15 565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported. Conclusion Comparison of different eradication treatments for H pylori showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of H pylori.

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases

Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%–93.9%) for KRAS, 96.8% (95% CI: 94.8%–98.0%) for BRAF, 93.9% (95% CI: 89.7%–96.5%) for PIK3CA and 71.7% (95% CI: 57.6%–82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%–12.4%) and 11.3% (95% CI: 8.0%–15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.

Effects of dietary fibre type on blood pressure: a systematic review and meta-analysis of randomized controlled trials of healthy individuals.

Objective: To determine the effect of different types of dietary fibre on SBP and DBP. Methods: A systematic review of the literature and a meta-analysis of randomized controlled trials using random-effects models. Eligibility criteria for studies included randomized controlled trials of at least 6 weeks duration, testing a fibre isolate or fibre-rich diet against a control or placebo published between 1 January 1990 and 1 December 2013. Results: Twenty-eight trials met the inclusion criteria and reported fibre intake and SBP and/or DBP. Eighteen trials were included in a meta-analysis. Studies were categorized into 1 of 12 fibre-type categories. The pooled estimates for all fibre types were −0.9 mmHg [95% confidence interval (CI) −2.5 to 0.6 mmHg] and −0.7 mmHg (95% CI −1.9 to 0.5 mmHg) for SBP and DBP, respectively. The median difference in total fibre was 6 g. Analyses of specific fibre types concluded that diets rich in beta-glucans reduce SBP by 2.9 mmHg (95% CI 0.9 to 4.9 mmHg) and DBP by 1.5 mmHg (95% CI 0.2 to 2.7 mmHg) for a median difference in beta-glucans of 4 g. Heterogeneity for individual fibre types was generally low. Conclusions: Higher consumption of beta-glucan fibre is associated with lower SBP and DBP. The results of this review are consistent with recommendations to increase consumption of foods rich in dietary fibre, but some additional emphasis on sources of beta-glucans, such as oats and barley, may be warranted.

Systematic review with network meta-analysis: comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity.

Many strategies are used to prevent nonsteroidal anti‐inflammatory drug (NSAID)‐associated gastrointestinal toxicity, but the comparative effectiveness remains unclear.

The method quality of cross-over studies involved in Cochrane Systematic Reviews.

Background It is possible that cross-over studies included in current systematic reviews are being inadequately assessed, because the current risk of bias tools do not consider possible biases specific to cross-over design. We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Reviews (CSRs). Methods We searched the Cochrane Library (up to 2013 issue 5) for CSRs that included at least one cross-over trial. Two authors independently undertook the study selection and data extraction. A random sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane handbook. In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane handbook. Results We identified 688 CSRs that included one or more cross-over studies. We chose a random sample of 60 CSRs and these included 139 cross-over studies. None of these CSRs undertook a risk of bias assessment specific for cross-over studies. In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs. When we reassessed the risk of bias, including the 3 items specific to cross-over trials, of these 139 studies, a low risk of bias was judged for appropriate cross-over design in 110(79%), carry-over effects in 48(34%) and for reporting data in all stages of the trial in 114(82%).Assessment of biases in cross-over trials could affect the GRADE assessment of a review’s findings. Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies. Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs. A proposed check list for the evaluation of cross-over trials is provided.

The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis

Objectives Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. Results A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8). Materials and Methods PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data. Conclusion This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.