Regressions and meta-regressions are widely used to estimate patterns and effect sizes in various disciplines. However, many biological and medical analyses use relatively low sample size (N), ...contributing to concerns on reproducibility. What is the minimum N to identify the most plausible data pattern using regressions? Statistical power analysis is often used to answer that question, but it has its own problems and logically should follow model selection to first identify the most plausible model. Here we make null, simple linear and quadratic data with different variances and effect sizes. We then sample and use information theoretic model selection to evaluate minimum N for regression models. We also evaluate the use of coefficient of determination (R2) for this purpose; it is widely used but not recommended. With very low variance, both false positives and false negatives occurred at N < 8, but data shape was always clearly identified at N ≥ 8. With high variance, accurate inference was stable at N ≥ 25. Those outcomes were consistent at different effect sizes. Akaike Information Criterion weights (AICc wi) were essential to clearly identify patterns (e.g., simple linear vs. null); R2 or adjusted R2 values were not useful. We conclude that a minimum N = 8 is informative given very little variance, but minimum N ≥ 25 is required for more variance. Alternative models are better compared using information theory indices such as AIC but not R2 or adjusted R2. Insufficient N and R2-based model selection apparently contribute to confusion and low reproducibility in various disciplines. To avoid those problems, we recommend that research based on regressions or meta-regressions use N ≥ 25.
Pulmonary endarterectomy (PEA) is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension (CTEPH). It is a complex surgical ...procedure with a simple principle: removal of obstructive thromboembolic material from the pulmonary arteries in order to reduce pulmonary vascular resistance, relieve pulmonary hypertension (PH) and alleviate right ventricular dysfunction. In the majority of patients there is symptomatic and prognostic benefit. However, not all patients with CTEPH are suitable for treatment with PEA. Operability assessment is not always easy, being largely subjective and based on experience. It is therefore important that all patients are referred to an experienced CTEPH centre for careful evaluation of suitability for surgery. The most common reason for inoperability is distal vasculopathy accounting for a high proportion of the vascular resistance. Surgery requires cardiopulmonary bypass and periods of deep hypothermic circulatory arrest. Complications include reperfusion lung injury and persistent PH. However, with careful patient selection, surgical technique and post-operative management, PEA is a highly effective treatment with mortality rates <5% at experienced centres. Patients who are unsuitable for surgery may be candidates for medical therapy.
Major scholars in the field, on the basis of a 3-day consensus, created an in-depth review of current knowledge on the role of diet in cardiovascular disease (CVD), the changing global food system ...and global dietary patterns, and potential policy solutions. Evidence from different countries and age/race/ethnicity/socioeconomic groups suggesting the health effects studies of foods, macronutrients, and dietary patterns on CVD appear to be far more consistent though regional knowledge gaps is highlighted. Large gaps in knowledge about the association of macronutrients to CVD in low- and middle-income countries particularly linked with dietary patterns are reviewed. Our understanding of foods and macronutrients in relationship to CVD is broadly clear; however, major gaps exist both in dietary pattern research and ways to change diets and food systems. On the basis of the current evidence, the traditional Mediterranean-type diet, including plant foods and emphasis on plant protein sources provides a well-tested healthy dietary pattern to reduce CVD.
The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause ...mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin with a statin for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.
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The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on ...glycemic control in individuals with diabetes.
We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA(1c)) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) statistic. Trial quality was assessed by the Heyland methodological quality score (MQS).
Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD -0.25 95% CI -0.46 to -0.04; P = 0.02) with significant intertrial heterogeneity (I(2) = 63%; P = 0.001). This reduction is equivalent to a ~0.53% reduction in HbA(1c). Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point.
Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required.
Abstract Background In the absence of consistent clinical evidence, concerns have been raised that fructose raises postprandial triglycerides. Purpose A systematic review and meta-analysis was ...conducted to assess the effect of fructose on postprandial triglycerides. Data sources Relevant studies were identified from MEDLINE, EMBASE, and Cochrane databases (through September 3, 2013). Data selection Relevant clinical trials of ≥7-days were included in the analysis. Data extraction Two independent reviewers extracted relevant data with disagreements reconciled by consensus. The Heyland Methodological Quality Score (MQS) assessed study quality. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed (Cochran Q statistic) and quantified ( I2 statistic). Data synthesis Eligibility criteria were met by 14 isocaloric trials ( n = 290), in which fructose was exchanged isocalorically for other carbohydrate in the diet, and two hypercaloric trials ( n = 33), in which fructose supplemented the background diet with excess energy from high-dose fructose compared with the background diet alone (without the excess energy). There was no significant effect in the isocaloric trials (SMD: 0.14 95% CI: −0.02, 0.30) with evidence of considerable heterogeneity explained by a single trial. Hypercaloric trials, however, showed a significant postprandial triglyceride raising-effect of fructose (SMD: 0.65 95% CI: 0.30, 1.01). Limitations Most of the available trials were small, short, and of poor quality. Interpretation of the isocaloric trials is complicated by the large influence of a single trial. Conclusions Pooled analyses show that fructose in isocaloric exchange for other carbohydrate does not increase postprandial triglycerides, although an effect cannot be excluded under all conditions. Fructose providing excess energy does increase postprandial triglycerides. Larger, longer, and higher-quality trials are needed. Protocol registration ClinicalTrials.gov identifier, NCT01363791.
Antioxidants have been promoted for cardiovascular disease (CVD) risk reduction and for the prevention of cancer. Our preliminary analysis suggested that only when selenium was present were ...antioxidant mixtures associated with reduced all-cause mortality.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effect of selenium supplementation alone and of antioxidant mixtures with or without selenium on the risk of CVD, cancer, and mortality.
We identified studies using the Cochrane Library, Medline, and Embase for potential CVD outcomes, cancer, and all-cause mortality following selenium supplementation alone or after antioxidant supplement mixtures with and without selenium up to June 5, 2020. RCTs of ≥24 wk were included and data were analyzed using random-effects models and classified by the Grading of Recommendations, Assessment, Development, and Evaluation approach.
The meta-analysis identified 9423 studies, of which 43 were used in the final analysis. Overall, no association of selenium alone or antioxidants was seen with CVD and all-cause mortality. However, a decreased risk with antioxidant mixtures was seen for CVD mortality when selenium was part of the mix (RR: 0.77; 95% CI: 0.62, 0.97; P = 0.02), with no association when selenium was absent. Similarly, when selenium was part of the antioxidant mixture, a decreased risk was seen for all-cause mortality (RR: 0.90; 95% CI: 0.82, 0.98; P = 0.02) as opposed to an increased risk when selenium was absent (RR: 1.09; 95% CI: 1.04, 1.13; P = 0.0002).
The addition of selenium should be considered for supplements containing antioxidant mixtures if they are to be associated with CVD and all-cause mortality risk reduction. This trial was registered at https://www.crd.york.ac.uk/PROSPERO/ as CRD42019138268.
Concerns have been raised about the adverse effect of fructose on blood pressure. International dietary guidelines, however, have not addressed fructose intake directly. A systematic review and ...meta-analysis was conducted to assess the effect of fructose in isocaloric exchange for other carbohydrates on systolic, diastolic, and mean arterial blood pressures. Studies were identified using Medline, Embase, and Cochrane databases (through January 9, 2012). Human clinical trials of isocaloric oral fructose exchange for other carbohydrate sources for ≥7 days were included in the analysis. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences with 95% CI. Heterogeneity was assessed by the Q-statistic and quantified by I(2). Study quality was assessed using the Heyland Methodological Quality Score. Thirteen isocaloric (n=352) and 2 hypercaloric (n=24) trials met the eligibility criteria. Overall, fructose intake in isocaloric exchange for other carbohydrates significantly decreased diastolic (mean difference: -1.54 95% CI: -2.77 to -0.32) and mean arterial pressure (mean difference: -1.16 95% CI: -2.15 to -0.18). There was no significant effect of fructose on systolic blood pressure (mean difference: -1.10 95% CI: -2.46 to 0.44). The hypercaloric fructose feeding trials found no significant overall mean arterial blood pressure effect of fructose in comparison with other carbohydrates. To confirm these results, longer and larger trials are needed. Contrary to previous concerns, we found that isocaloric substitution of fructose for other carbohydrates did not adversely affect blood pressure in humans.
Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.
To provide better evidence for diabetes ...guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.
MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.
Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.
Two independent reviewer's extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI's. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2).
Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = -0.07% 95% CI:-0.10, -0.03%; P = 0.0003) and fasting glucose (MD = -0.15 mmol/L 95% CI: -0.27, -0.02 mmol/L; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.
Majority of trials were of short duration and poor quality.
Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.
ClinicalTrials.gov NCT01630980.
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