Sensitivity and Specificity of Using GPT-3.5 Turbo Models for Title and Abstract Screening in Systematic Reviews and Meta-analyses.

BACKGROUND: Systematic reviews are performed manually despite the exponential growth of scientific literature. OBJECTIVE: To investigate the sensitivity and specificity of GPT-3.5 Turbo, from OpenAI, as a single reviewer, for title and abstract screening in systematic reviews. DESIGN: Diagnostic test accuracy study. SETTING: Unannotated bibliographic databases from 5 systematic reviews representing 22 665 citations. PARTICIPANTS: None. MEASUREMENTS: A generic prompt framework to instruct GPT to perform title and abstract screening was designed. The output of the model was compared with decisions from authors under 2 rules. The first rule balanced sensitivity and specificity, for example, to act as a second reviewer. The second rule optimized sensitivity, for example, to reduce the number of citations to be manually screened. RESULTS: Under the balanced rule, sensitivities ranged from 81.1% to 96.5% and specificities ranged from 25.8% to 80.4%. Across all reviews, GPT identified 7 of 708 citations (1%) missed by humans that should have been included after full-text screening at the cost of 10 279 of 22 665 false-positive recommendations (45.3%) that would require reconciliation during the screening process. Under the sensitive rule, sensitivities ranged from 94.6% to 99.8% and specificities ranged from 2.2% to 46.6%. Limiting manual screening to citations not ruled out by GPT could reduce the number of citations to screen from 127 of 6334 (2%) to 1851 of 4077 (45.4%), at the cost of missing from 0 to 1 of 26 citations (3.8%) at the full-text level. LIMITATIONS: Time needed to fine-tune prompt. Retrospective nature of the study, convenient sample of 5 systematic reviews, and GPT performance sensitive to prompt development and time. CONCLUSION: The GPT-3.5 Turbo model may be used as a second reviewer for title and abstract screening, at the cost of additional work to reconcile added false positives. It also showed potential to reduce the number of citations before screening by humans, at the cost of missing some citations at the full-text level. PRIMARY FUNDING SOURCE: None.

Evaluating agreement between evidence from randomised controlled trials and cohort studies in nutrition: a meta-research replication study.

This meta-research study aims to evaluate the agreement of effect estimates between bodies of evidence (BoE) from RCTs and cohort studies included in the same nutrition evidence synthesis, to identify factors associated with disagreement, and to replicate the findings of a previous study. We searched Medline, Epistemonikos and the Cochrane Database of Systematic Reviews for nutrition systematic reviews that included both RCTs and cohort studies for the same patient-relevant outcome or intermediate-disease marker. We rated similarity of PI/ECO (population, intervention/exposure, comparison, outcome) between BoE from RCTs and cohort studies. Agreement of effect estimates across BoE was analysed by pooling ratio of risk ratios (RRR) for binary outcomes and difference of standardised mean differences (DSMD) for continuous outcomes. We performed subgroup and sensitivity analyses to explore determinants associated with disagreements. We included 82 BoE-pairs from 51 systematic reviews. For binary outcomes, the RRR was 1.04 (95% confidence interval (CI) 0.99 to 1.10, I2 = 59%, τ2 = 0.02, prediction interval (PI) 0.77 to 1.41). For continuous outcomes, the pooled DSMD was - 0.09 (95% CI - 0.26 to 0.09, PI - 0.55 to 0.38). Subgroup analyses yielded that differences in type of intake/exposure were drivers towards disagreement. We replicated the findings of a previous study, where on average RCTs and cohort studies had similar effect estimates. Disagreement and wide prediction intervals were mainly driven by PI/ECO-dissimilarities. More research is needed to explore other potentially influencing factors (e.g. risk of bias) on the disagreement between effect estimates of both BoE.Trial registration: CRD42021278908.

Protein intake and type 2 diabetes mellitus: an umbrella review of systematic reviews for the evidence-based guideline for protein intake of the German Nutrition Society.

PURPOSE: Protein-rich foods show heterogeneous associations with the risk of type 2 diabetes (T2D) and it remains unclear whether habitual protein intake is related to T2D risk. We carried out an umbrella review of systematic reviews (SR) of randomised trials and/or cohort studies on protein intake in relation to risks of T2D. METHODS: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and T2D risk published between July 1st 2009 and May 22nd 2022, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. RESULTS: Eight SRs were identified of which six contained meta-analyses. The majority of SRs on total protein intake had moderate or high methodological quality and moderate outcome-specific certainty of evidence according to NutriGrade, however, the latter was low for the majority of SRs on animal and plant protein. Six of the eight SRs reported risk increases with both total and animal protein. According to one SR, total protein intake in studies was ~ 21 energy percentage (%E) in the highest intake category and 15%E in the lowest intake category. Relative Risks comparing high versus low intake in most recent SRs ranged from 1.09 (two SRs, 95% CIs 1.02-1.15 and 1.06-1.13) to 1.11 (1.05-1.16) for total protein (between 8 and 12 cohort studies included) and from 1.13 (1.08-1.19) to 1.19 (two SRs, 1.11-1.28 and 1.11-1.28) (8-9 cohort studies) for animal protein. However, SRs on RCTs examining major glycaemic traits (HbA1c, fasting glucose, fasting insulin) do not support a clear biological link with T2D risk. For plant protein, some recent SRs pointed towards risk decreases and non-linear associations, however, the majority did not support an association with T2D risk. CONCLUSION: Higher total protein intake was possibly associated with higher T2D risk, while there is insufficient evidence for a risk increase with higher intakes of animal protein and a risk decrease with plant protein intake. Given that most SRs on plant protein did not indicate an association, there is possibly a lack of an effect.

Protein intake and body weight, fat mass and waist circumference: an umbrella review of systematic reviews for the evidence-based guideline on protein intake of the German Nutrition Society.

PURPOSE: This umbrella review aimed to assess whether dietary protein intake with regard to quantitative (higher vs. lower dietary protein intake) and qualitative considerations (total, plant-based or animal-based protein intake) affects body weight (BW), fat mass (FM) and waist circumference (WC). METHODS: A systematic literature search was conducted in PubMed, Embase and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with and without meta-analyses of prospective studies published between 04 October 2007 and 04 January 2022. Methodological quality and outcome-specific certainty of evidence of the retrieved SRs were assessed by using AMSTAR 2 and NutriGrade, respectively, in order to rate the overall certainty of evidence using predefined criteria. RESULTS: Thirty-three SRs were included in this umbrella review; 29 were based on randomised controlled trials, a few included cohort studies. In studies without energy restriction, a high-protein diet did not modulate BW, FM and WC in adults in general (all "possible" evidence); for older adults, overall certainty of evidence was "insufficient" for all parameters. Under hypoenergetic diets, a high-protein diet mostly decreased BW and FM, but evidence was "insufficient" due to low methodological quality. Evidence regarding an influence of the protein type on BW, FM and WC was "insufficient". CONCLUSION: "Possible" evidence exists that the amount of protein does not affect BW, FM and WC in adults under isoenergetic conditions. Its impact on the reduction in BW and FM under hypoenergetic conditions remains unclear; evidence for an influence of protein type on BW, FM and WC is "insufficient".

Protein intake and cancer: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

PURPOSE: It has been proposed that a higher habitual protein intake may increase cancer risk, possibly via upregulated insulin-like growth factor signalling. Since a systematic evaluation of human studies on protein intake and cancer risk based on a standardised assessment of systematic reviews (SRs) is lacking, we carried out an umbrella review of SRs on protein intake in relation to risks of different types of cancer. METHODS: Following a pre-specified protocol (PROSPERO: CRD42018082395), we retrieved SRs on protein intake and cancer risk published before January 22th 2024, and assessed the methodological quality and outcome-specific certainty of the evidence using a modified version of AMSTAR 2 and NutriGrade, respectively. The overall certainty of evidence was rated according to predefined criteria. RESULTS: Ten SRs were identified, of which eight included meta-analyses. Higher total protein intake was not associated with risks of breast, prostate, colorectal, ovarian, or pancreatic cancer incidence. The methodological quality of the included SRs ranged from critically low (kidney cancer), low (pancreatic, ovarian and prostate cancer) and moderate (breast and prostate cancer) to high (colorectal cancer). The outcome-specific certainty of the evidence underlying the reported findings on protein intake and cancer risk ranged from very low (pancreatic, ovarian and prostate cancer) to low (colorectal, ovarian, prostate, and breast cancer). Animal and plant protein intakes were not associated with cancer risks either at a low (breast and prostate cancer) or very low (pancreatic and prostate cancer) outcome-specific certainty of the evidence. Overall, the evidence for the lack of an association between protein intake and (i) colorectal cancer risk and (ii) breast cancer risk was rated as possible. By contrast, the evidence underlying the other reported results was rated as insufficient. CONCLUSION: The present findings suggest that higher total protein intake may not be associated with the risk of colorectal and breast cancer, while conclusions on protein intake in relation to risks of other types of cancer are restricted due to insufficient evidence.

Dietary protein and blood pressure: an umbrella review of systematic reviews and evaluation of the evidence.

INTRODUCTION: This umbrella review aimed to investigate the evidence of an effect of dietary intake of total protein, animal and plant protein on blood pressure (BP), and hypertension (PROSPERO: CRD42018082395). METHODS: PubMed, Embase and Cochrane Database were systematically searched for systematic reviews (SRs) of prospective studies with or without meta-analysis published between 05/2007 and 10/2022. The methodological quality and outcome-specific certainty of evidence were assessed by the AMSTAR 2 and NutriGrade tools, followed by an assessment of the overall certainty of evidence. SRs investigating specific protein sources are described in this review, but not included in the assessment of the overall certainty of evidence. RESULTS: Sixteen SRs were considered eligible for the umbrella review. Ten of the SRs investigated total protein intake, six animal protein, six plant protein and four animal vs. plant protein. The majority of the SRs reported no associations or effects of total, animal and plant protein on BP (all "possible" evidence), whereby the uncertainty regarding the effects on BP was particularly high for plant protein. Two SRs addressing milk-derived protein showed a reduction in BP; in contrast, SRs investigating soy protein found no effect on BP. The outcome-specific certainty of evidence of the SRs was mostly rated as low. DISCUSSION/CONCLUSION: This umbrella review showed uncertainties whether there are any effects on BP from the intake of total protein, or animal or plant proteins, specifically. Based on data from two SRs with milk protein, it cannot be excluded that certain types of protein could favourably influence BP.

Nutritional interventions for preventing and treating pressure ulcers.

BACKGROUND: Pressure ulcers are localized injuries to the skin or the underlying tissue, or both, and are common in older and immobile people, people with diabetes, vascular disease, or malnutrition, as well as those who require intensive or palliative care. People with pressure ulcers often suffer from severe pain and exhibit social avoidance behaviours. The prevention and treatment of pressure ulcers involves strategies to optimize hydration, circulation, and nutrition. Adequate nutrient intake can reduce the risk factor of malnutrition and promote wound healing in existing pressure ulcers. However, it is unclear which nutrients help prevent and treat pressure ulcers. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of nutritional interventions (special diets, supplements) for preventing and treating pressure ulcers in people with or without existing pressure ulcers compared to standard diet or other nutritional interventions. SEARCH METHODS: We used extensive Cochrane search methods. The latest search was in May 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in people with or without existing pressure ulcers, that compared nutritional interventions aimed at preventing or treating pressure ulcers with standard diet or other types of nutritional interventions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome for prevention studies was the proportion of participants who developed new (incident) pressure ulcers. For treatment studies, our primary outcomes were time to complete pressure ulcer healing, number of people with healed pressure ulcers, size and depth of pressure ulcers, and rate of pressure ulcer healing. Secondary outcomes were side effects, costs, health-related quality of life and acceptability. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 33 RCTs with 7920 participants. Data for meta-analysis were available from 6993 participants. Pressure ulcer prevention Eleven studies (with 12 arms) compared six types of nutritional interventions for the prevention of pressure ulcers. Compared to standard diet, energy, protein and micronutrient supplements may result in little to no difference in the proportion of participants developing a pressure ulcer (energy, protein and micronutrient supplements 248 per 1000, standard diet 269 per 1000; RR 0.92, 95% CI 0.71 to 1.19; 3 studies, 1634 participants; low-certainty evidence). Compared to standard diet, protein supplements may result in little to no difference in pressure ulcer incidence (protein 21 per 1000, standard diet 28 per 1000; RR 0.75, 95% CI 0.49 to 1.14; 4 studies, 4264 participants; low-certainty evidence). The evidence is very uncertain about the gastrointestinal side effects of these supplements (protein 109 per 1000, standard diet 155 per 1000; RR 0.70, 95% CI 0.06 to 7.96; 2 studies, 140 participants, very low-certainty evidence). The evidence is very uncertain about the effects of protein, arginine, zinc and antioxidants; L-carnitine, L-leucine, calcium, magnesium and vitamin D; EPA, GLA and antioxidants; disease-specific supplements on pressure ulcer incidence when compared to standard diet (1 study each; very low-certainty evidence for all comparisons). Pressure ulcer treatment Twenty-four studies (with 27 arms) compared 10 types of nutritional interventions or supplements for treatment of pressure ulcers. Compared to standard diet, energy, protein and micronutrient supplements may slightly increase the number of healed pressure ulcers (energy, protein and micronutrients 366 per 1000, standard diet 253 per 1000; RR 1.45, 95% CI 1.14 to 1.85; 3 studies, 577 participants, low-certainty evidence). The evidence is very uncertain about the effect of these supplements on gastrointestinal side effects. Compared to standard diet, the evidence is very uncertain about the effect of protein, arginine, zinc and antioxidant supplements on pressure ulcer healing (pressure ulcer area: mean difference (MD) 2 cm² smaller, 95% CI 4.54 smaller to 0.53 larger; 2 studies, 71 participants, very low-certainty evidence). The evidence on side effects of these supplements is very uncertain. Compared to standard diet, supplements with arginine and micronutrients may not increase the number of healed pressure ulcers, but the evidence suggests a slight reduction in pressure ulcer area (MD 15.8% lower, 95% CI 25.11 lower to 6.48 lower; 2 studies, 231 participants, low-certainty evidence). The evidence is very uncertain about changes in pressure ulcer scores, acceptability, and side effects of these supplements. Compared to placebo, collagen supplements probably improve the mean change in pressure ulcer area (MD 1.81 cm² smaller, 95% CI 3.36 smaller to 0.26 smaller; 1 study, 74 participants, moderate-certainty evidence). The evidence is very uncertain about the effect of these supplements on side effects. The evidence is very uncertain about the effects of vitamin C, different doses of arginine; EPA, GLA (special dietary fatty acids) and antioxidants; protein; a specialized amino acid mixture; ornithine alpha-ketoglutarate and zinc supplements on pressure ulcer healing (1 or 2 studies each; very low-certainty evidence). AUTHORS' CONCLUSIONS: The benefits of nutritional interventions with various compositions for pressure ulcer prevention and treatment are uncertain. There may be little or no difference compared to standard nutrition or placebo. Nutritional supplements may not increase gastrointestinal side effects, but the evidence is very uncertain. Larger studies with similar nutrient compositions would reduce these uncertainties. No study investigated the effects of special diets (e.g. protein-enriched diet, vegetarian diet) on pressure ulcer incidence and healing.

Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials: a meta-epidemiological study.

BACKGROUND: Researchers and decision-makers often use evidence from randomised controlled trials (RCTs) to determine the efficacy or effectiveness of a treatment or intervention. Studies with observational designs are often used to measure the effectiveness of an intervention in 'real world' scenarios. Numerous study designs and their modifications (including both randomised and observational designs) are used for comparative effectiveness research in an attempt to give an unbiased estimate of whether one treatment is more effective or safer than another for a particular population. An up-to-date systematic analysis is needed to identify differences in effect estimates from RCTs and observational studies. This updated review summarises the results of methodological reviews that compared the effect estimates of observational studies with RCTs from evidence syntheses that addressed the same health research question. OBJECTIVES: To assess and compare synthesised effect estimates by study type, contrasting RCTs with observational studies. To explore factors that might explain differences in synthesised effect estimates from RCTs versus observational studies (e.g. heterogeneity, type of observational study design, type of intervention, and use of propensity score adjustment). To identify gaps in the existing research comparing effect estimates across different study types. SEARCH METHODS: We searched MEDLINE, the Cochrane Database of Systematic Reviews, Web of Science databases, and Epistemonikos to May 2022. We checked references, conducted citation searches, and contacted review authors to identify additional reviews. SELECTION CRITERIA: We included systematic methodological reviews that compared quantitative effect estimates measuring the efficacy or effectiveness of interventions tested in RCTs versus in observational studies. The included reviews compared RCTs to observational studies (including retrospective and prospective cohort, case-control and cross-sectional designs). Reviews were not eligible if they compared RCTs with studies that had used some form of concurrent allocation. DATA COLLECTION AND ANALYSIS: Using results from observational studies as the reference group, we examined the relative summary effect estimates (risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), mean differences (MDs), and standardised mean differences (SMDs)) to evaluate whether there was a relatively larger or smaller effect in the ratio of odds ratios (ROR) or ratio of risk ratios (RRR), ratio of hazard ratios (RHR), and difference in (standardised) mean differences (D(S)MD). If an included review did not provide an estimate comparing results from RCTs with observational studies, we generated one by pooling the estimates for observational studies and RCTs, respectively. Across all reviews, we synthesised these ratios to produce a pooled ratio of ratios comparing effect estimates from RCTs with those from observational studies. In overviews of reviews, we estimated the ROR or RRR for each overview using observational studies as the reference category. We appraised the risk of bias in the included reviews (using nine criteria in total). To receive an overall low risk of bias rating, an included review needed: explicit criteria for study selection, a complete sample of studies, and to have controlled for study methodological differences and study heterogeneity. We assessed reviews/overviews not meeting these four criteria as having an overall high risk of bias. We assessed the certainty of the evidence, consisting of multiple evidence syntheses, with the GRADE approach. MAIN RESULTS: We included 39 systematic reviews and eight overviews of reviews, for a total of 47. Thirty-four of these contributed data to our primary analysis. Based on the available data, we found that the reviews/overviews included 2869 RCTs involving 3,882,115 participants, and 3924 observational studies with 19,499,970 participants. We rated 11 reviews/overviews as having an overall low risk of bias, and 36 as having an unclear or high risk of bias. Our main concerns with the included reviews/overviews were that some did not assess the quality of their included studies, and some failed to account appropriately for differences between study designs - for example, they conducted aggregate analyses of all observational studies rather than separate analyses of cohort and case-control studies. When pooling RORs and RRRs, the ratio of ratios indicated no difference or a very small difference between the effect estimates from RCTs versus from observational studies (ratio of ratios 1.08, 95% confidence interval (CI) 1.01 to 1.15). We rated the certainty of the evidence as low. Twenty-three of 34 reviews reported effect estimates of RCTs and observational studies that were on average in agreement. In a number of subgroup analyses, small differences in the effect estimates were detected: - pharmaceutical interventions only (ratio of ratios 1.12, 95% CI 1.04 to 1.21); - RCTs and observational studies with substantial or high heterogeneity; that is, I2 ≥ 50% (ratio of ratios 1.11, 95% CI 1.04 to 1.18); - no use (ratio of ratios 1.07, 95% CI 1.03 to 1.11) or unclear use (ratio of ratios 1.13, 95% CI 1.03 to 1.25) of propensity score adjustment in observational studies; and - observational studies without further specification of the study design (ratio of ratios 1.06, 95% CI 0.96 to 1.18). We detected no clear difference in other subgroup analyses. AUTHORS' CONCLUSIONS: We found no difference or a very small difference between effect estimates from RCTs and observational studies. These findings are largely consistent with findings from recently published research. Factors other than study design need to be considered when exploring reasons for a lack of agreement between results of RCTs and observational studies, such as differences in the population, intervention, comparator, and outcomes investigated in the respective studies. Our results underscore that it is important for review authors to consider not only study design, but the level of heterogeneity in meta-analyses of RCTs or observational studies. A better understanding is needed of how these factors might yield estimates reflective of true effectiveness.

Current Guidelines on Fat Intake in Pregnant and Lactating Women, Infants, Children, and Adolescents: A Scoping Review.

INTRODUCTION: Dietary fat intake in pregnancy, lactation, and childhood determines child growth, neurodevelopment, and long-term health. METHODS: We performed a scoping review of dietary guidelines on fat intake for pregnant and lactating women, infants, children, and adolescents. We systematically searched several databases and websites for relevant documents published in English from 2015 to 2019. RESULTS: We included 14 documents. Of those, eight targeted pregnant and/or lactating women, mainly recommending daily intake of approx. 250 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), while one advised supplementing 800 mg/d DHA and 100 mg/d EPA in women of low omega-3 fatty acid status. The number of guidelines for infants was low (n = 3). Recommended intakes of total fat were 30-40% and 20-35% of total energy intake (TEI) for infants and children, respectively. Intakes of saturated fatty acids (SFAs) <10% of TEI and avoidance of trans-fatty acids (TFAs) were recommended across childhood. The methodology applied to develop guidelines and to grade the strength of recommendations was heterogeneous. CONCLUSION: Quantitative recommendations on fat intake during pregnancy focused mainly on PUFA intake, and those targeting infants were limited. Consistent recommendations were provided for total fat, SFA, and TFA intake in childhood; however, strength of recommendation was mostly not reported.

Substitution of animal-based with plant-based foods on cardiometabolic health and all-cause mortality: a systematic review and meta-analysis of prospective studies.

BACKGROUND: There is growing evidence that substituting animal-based with plant-based foods is associated with a lower risk of cardiovascular diseases (CVD), type 2 diabetes (T2D), and all-cause mortality. Our aim was to summarize and evaluate the evidence for the substitution of any animal-based foods with plant-based foods on cardiometabolic health and all-cause mortality in a systematic review and meta-analysis. METHODS: We systematically searched MEDLINE, Embase, and Web of Science to March 2023 for prospective studies investigating the substitution of animal-based with plant-based foods on CVD, T2D, and all-cause mortality. We calculated summary hazard ratios (SHRs) and 95% confidence intervals (95% CI) using random-effects meta-analyses. We assessed the certainty of evidence (CoE) using the GRADE approach. RESULTS: In total, 37 publications based on 24 cohorts were included. There was moderate CoE for a lower risk of CVD when substituting processed meat with nuts [SHR (95% CI): 0.73 (0.59, 0.91), n = 8 cohorts], legumes [0.77 (0.68, 0.87), n = 8], and whole grains [0.64 (0.54, 0.75), n = 7], as well as eggs with nuts [0.83 (0.78, 0.89), n = 8] and butter with olive oil [0.96 (0.95, 0.98), n = 3]. Furthermore, we found moderate CoE for an inverse association with T2D incidence when substituting red meat with whole grains/cereals [0.90 (0.84, 0.96), n = 6] and red meat or processed meat with nuts [0.92 (0.90, 0.94), n = 6 or 0.78 (0.69, 0.88), n = 6], as well as for replacing poultry with whole grains [0.87 (0.83, 0.90), n = 2] and eggs with nuts or whole grains [0.82 (0.79, 0.86), n = 2 or 0.79 (0.76, 0.83), n = 2]. Moreover, replacing red meat for nuts [0.93 (0.91, 0.95), n = 9] and whole grains [0.96 (0.95, 0.98), n = 3], processed meat with nuts [0.79 (0.71, 0.88), n = 9] and legumes [0.91 (0.85, 0.98), n = 9], dairy with nuts [0.94 (0.91, 0.97), n = 3], and eggs with nuts [0.85 (0.82, 0.89), n = 8] and legumes [0.90 (0.89, 0.91), n = 7] was associated with a reduced risk of all-cause mortality. CONCLUSIONS: Our findings indicate that a shift from animal-based (e.g., red and processed meat, eggs, dairy, poultry, butter) to plant-based (e.g., nuts, legumes, whole grains, olive oil) foods is beneficially associated with cardiometabolic health and all-cause mortality.

Protein intake and bone health: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

This umbrella review aimed at assessing whether a protein intake exceeding the current recommendation for younger (0.8 g/kg body weight [BW]/day) and older (1.0 g/kg BW/day) adults affects bone mineral density and fracture risk. Moreover, the effect of animal or plant protein was evaluated. A systematic literature search was conducted in PubMed, Embase, and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with or without meta-analysis of prospective studies published between 11/2008 and 08/2021. Methodological quality, outcome-specific certainty of evidence, and overall certainty of evidence of the retrieved SRs were assessed using established tools and predefined criteria. Eleven SRs of randomized controlled trials (RCTs) and/or cohort studies were included. In SRs of cohort studies and RCTs, protein intake/kg BW/day ranged between 0.21-0.95 g (low intake) and > 1.24 g (high intake), respectively, and between 0.67-1.1 g (control groups) and 1.01-1.69 g (intervention groups), respectively. The vast majority of outcome-specific certainty of evidence was rated "low" or "very low." The overall certainty of evidence for an association (cohort studies) or effect (RCTs) of total, animal or plant protein intake on each of the investigated outcomes was rated "insufficient," with the exception of possible evidence for a reduced hip fracture risk by high vs. low protein intake. Since protein intakes in low/control and high/intervention groups were very heterogeneous and with low certainty of evidence, it remains unclear whether a dose above the current recommendation or type of protein intake (animal or plant protein) affects bone health overall. However, there is possible evidence for reduced hip fracture risk with high versus low protein intake.

Coconut Oil and Cardiovascular Disease Risk.

PURPOSE OF REVIEW: This narrative review summarizes the current peer-reviewed literature and mechanisms surrounding the cardiovascular health impact of coconut oil. RECENT FINDINGS: No randomized controlled trials (RCTs) and/or prospective cohort studies have investigated the effect or association of coconut oil with cardiovascular disease. Evidence from RCTs indicated that coconut oil seems to have less detrimental effects on total and LDL-cholesterol compared to butter, but not compared to cis-unsaturated vegetable oils, such as safflower, sunflower, or canola oil. The isocaloric replacement (by 1% of energy intake) of carbohydrates with lauric acid (the predominant fatty acid in coconut oil) increased total cholesterol by 0.029 mmol/L (95% CI: 0.014; 0.045), LDL-cholesterol by 0.017 mmol/L (0.003; 0.031), and HDL-cholesterol by 0.019 mmol/L (0.016; 0.023). The current evidence from shorter term RCTs suggests that replacement of coconut oil with cis-unsaturated oils lowers total and LDL-cholesterol, whereas for the association between coconut oil intake and cardiovascular disease, less evidence is available.

Association of poultry consumption with cardiovascular diseases and all-cause mortality: a systematic review and dose response meta-analysis of prospective cohort studies.

According to previous cohort studies it is suggested that a high intake of poultry does not adversely affect cardiovascular disease (CVD) risk. Therefore, the aim of this systematic review and meta-analysis is to summarize and analyze the association between dietary poultry intake and the risk for CVDs, coronary heart disease (CHD), stroke and all-cause mortality (ACM). Twenty-four cohort studies were included, and the results showed a trivial inverse association for the highest vs. lowest intake category between poultry and ACM (risk ratio [RR] = 0.96; 95% CI: 0.93, 0.98; I2 = 5%). For all other outcomes no association was observed in the high vs. low intake meta-analysis. The results from the primary pooled data for each 100 g/d increase in poultry intake indicated no association for all outcomes. Further, the non-linear dose-response analysis showed some evidence for non-linearity between poultry consumption and risk for CVD and ACM. Additionally, substituting red and/or processed meat with poultry was inversely associated with the risk for ACM, CVDs, CHD and stroke. The certainty of evidence was rated as very low or low. This meta-analysis suggests that based upon the results from the substitution analyses poultry could be a healthier alternative to red and processed meat.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1975092.

Evidence of a vegan diet for health benefits and risks - an umbrella review of meta-analyses of observational and clinical studies.

To summarize and evaluate the evidence on the health impact of a vegan diet, we conducted an umbrella review of systematic reviews and meta-analyses. PubMed, Cochrane Library, Web of Science and Epistemonikos were searched up to September 2021. Meta-analyses were recalculated by using a random effects model. The certainty of evidence (CoE) was evaluated by the GRADE approach. For the general healthy population, a vegan diet was effective for reducing body weight [MD (95% CI): -2.52 kg (-3.06, -1.98), n = 8 RCTs; moderate CoE] and was associated with further health benefits (with low CoE), including a lower risk of cancer incidence [SRR (95% CI): 0.84 (0.75, 0.95), n = 2] and a trend for lower risk of all-cause mortality [SRR (95% CI): 0.87 (0.75, 1.01), n = 2], as well as lower ApoB levels [MD (95% CI): -0.19 µmol/L (-0.23, -0.15), n = 7 RCTs). The findings suggested adverse associations for a vegan diet with risk of fractures [SRR (95% CI): 1.46 (1.03, 2.07), n = 3; low CoE]. For persons with diabetes or at high CVD risk, a vegan diet reduced measures of adiposity, total cholesterol, LDL and improved glycemic control (CoE moderate to low). A vegan diet may have the potential for the prevention of cardiometabolic health, but it may also impair bone health. More well-conducted primary studies are warranted.

Protein intake and risk of urolithiasis and kidney diseases: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society.

PURPOSE: Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted. METHODS: PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria. RESULTS: Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as 'possible' for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as 'probable' or 'possible' for most other kidney function-related parameters to be physiologically increased with HPI. CONCLUSION: Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required.

Perspectives on the application of CONSORT guidelines to randomised controlled trials in nutrition.

PURPOSE: Reporting guidelines facilitate quality and completeness in research reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement is widely applied to dietary and nutrition trials but has no extension specific to nutrition. Evidence suggests poor reporting in nutrition research. The Federation of European Nutrition Societies led an initiative to make recommendations for a nutrition extension to the CONSORT statement towards a more robust reporting of the evidence base. METHODS: An international working group was formed of nutrition researchers from 14 institutions in 12 different countries and on five continents. Using meetings over a period of one year, we interrogated the CONSORT statement specifically for its application to report nutrition trials. RESULTS: We provide a total of 28 new nutrition-specific recommendations or emphasised recommendations for the reporting of the introduction (three), methods (twelve), results (five) and discussion (eight). We also added two additional recommendations that were not allocated under the standard CONSORT headings. CONCLUSION: We identify a need to provide guidance in addition to CONSORT to improve the quality and consistency of the reporting and propose key considerations for further development of formal guidelines for the reporting of nutrition trials. Readers are encouraged to engage in this process, provide comments and conduct specific studies to inform further work on the development of reporting guidelines for nutrition trials.

Fat Intake and Fat Quality in Pregnant and Lactating Women, Infants, Children, and Adolescents and Related Health Outcomes: A Scoping Review of Systematic Reviews of Prospective Studies.

INTRODUCTION: Dietary fat intake during pregnancy and childhood is important for health. However, several health aspects are inconclusive. METHODS: We systematically searched Medline, Cochrane Library, and Epistemonikos for systematic reviews (SRs) of randomized controlled trials (RCTs) and/or prospective cohort studies published from January 01, 2015, to December 31, 2019, assessing the association of dietary fat intake (including dietary supplements) during pregnancy and across childhood with pregnancy, perinatal, and child health outcomes. RESULTS: Thirty-one SRs, mainly of RCTs, were included. Omega-3 fatty acids supplementation during pregnancy reduced the risk of early preterm birth, and in some SRs also any preterm birth, increased gestation length and birth weight, but mostly was not associated with other pregnancy/perinatal outcomes. Pre- and postnatal polyunsaturated fatty acids (PUFAs) intake was not consistently associated with growth, neurological, visual and cognitive outcomes, allergic diseases, cardiovascular, and metabolic health in childhood. Reduced saturated fatty acids (SFAs) intake and its replacement with PUFA/monounsaturated fatty acids had favourable effects on blood pressure and blood lipids in children. No apparent effects of total or trans fat on health outcomes across target groups were observed. CONCLUSION: Omega-3 PUFA supplementation during pregnancy and SFA intake reduction in childhood require further consideration in dietary recommendations targeting these populations.

Empirical evidence of study design biases in nutrition randomised controlled trials: a meta-epidemiological study.

BACKGROUND: Instruments to critically appraise randomised controlled trials (RCTs) are based on evidence from meta-epidemiological studies. We aim to conduct a meta-epidemiological study on the average bias associated with reported methodological trial characteristics such as random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and compliance of RCTs in nutrition research. METHODS: We searched the Cochrane Database of Systematic Reviews, for systematic reviews of RCTs, published between 01 January 2010 and 31 December 2019. We combined the estimates of the average bias (e.g. ratio of risk ratios [RRR] or differences in standardised mean differences) in meta-analyses using the random-effects model. Subgroup analyses were conducted to investigate the potential differences among the RCTs with low versus high/unclear risk of bias with respect to the different types of interventions (e.g. micronutrients, fatty acids, dietary approach), outcomes (e.g. mortality, pregnancy outcomes), and type of outcome (objective, subjective). Heterogeneity was assessed through I2 and τ2, and prediction intervals were calculated. RESULTS: We included 27 Cochrane nutrition reviews with 77 meta-analyses (n = 927 RCTs). The available evidence suggests that intervention effect estimates may not be exaggerated in RCTs with high/unclear risk of bias (versus low) judgement for sequence generation (RRR 0.97, 95% CI 0.93 to 1.02; I2 = 28%; τ2 = 0.002), allocation concealment (RRR 1.00, 95% CI 0.96 to 1.04; I2 = 27%; τ2 = 0.001), blinding of participants and personnel (RRR 0.95, 95% CI 0.91 to 1.00; I2 = 23%; τ2 = 0), selective reporting (RRR 0.97, 95% CI 0.92 to 1.02; I2 = 24%; τ2 = 0), and compliance (RRR 0.95, 95% CI 0.89 to 1.02; I2 = 0%; τ2 = 0). Intervention effect estimates seemed to be exaggerated in RCTs with a high/unclear risk of bias judgement for blinding of outcome assessment (RRR 0.81, 95% CI 0.70 to 0.94; I2 = 26%; τ2 = 0.03), which was predominately driven by subjective outcomes, and incomplete outcome data (RRR 0.92, 95% CI 0.88 to 0.97; I2 = 22%; τ2 = 0.001). For continuous outcomes, no differences were observed, except for selective reporting. CONCLUSIONS: On average, most characteristics of nutrition RCTs may not exaggerate intervention effect estimates, but the average bias appears to be greatest in trials of subjective outcomes. Replication of this study is suggested in this field to keep this conclusion updated.

An empirical evaluation of the impact scenario of pooling bodies of evidence from randomized controlled trials and cohort studies in medical research.

BACKGROUND: Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess treatment effects of medical interventions. We aimed to hypothetically pool bodies of evidence (BoE) from RCTs with matched BoE from cohort studies included in the same systematic review. METHODS: BoE derived from systematic reviews of RCTs and cohort studies published in the 13 medical journals with the highest impact factor were considered. We re-analyzed effect estimates of the included systematic reviews by pooling BoE from RCTs with BoE from cohort studies using random and common effects models. We evaluated statistical heterogeneity, 95% prediction intervals, weight of BoE from RCTs to the pooled estimate, and whether integration of BoE from cohort studies modified the conclusion from BoE of RCTs. RESULTS: Overall, 118 BoE-pairs based on 653 RCTs and 804 cohort studies were pooled. By pooling BoE from RCTs and cohort studies with a random effects model, for 61 (51.7%) out of 118 BoE-pairs, the 95% confidence interval (CI) excludes no effect. By pooling BoE from RCTs and cohort studies, the median I2 was 48%, and the median contributed percentage weight of RCTs to the pooled estimates was 40%. The direction of effect between BoE from RCTs and pooled effect estimates was mainly concordant (79.7%). The integration of BoE from cohort studies modified the conclusion (by examining the 95% CI) from BoE of RCTs in 32 (27%) of the 118 BoE-pairs, but the direction of effect was mainly concordant (88%). CONCLUSIONS: Our findings provide insights for the potential impact of pooling both BoE in systematic reviews. In medical research, it is often important to rely on both evidence of RCTs and cohort studies to get a whole picture of an investigated intervention-disease association. A decision for or against pooling different study designs should also always take into account, for example, PI/ECO similarity, risk of bias, coherence of effect estimates, and also the trustworthiness of the evidence. Overall, there is a need for more research on the influence of those issues on potential pooling.

Evaluating agreement between bodies of evidence from randomized controlled trials and cohort studies in medical research: a meta-epidemiological study.

BACKGROUND: Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess the treatment effects of medical interventions. To evaluate the agreement of effect estimates between bodies of evidence (BoE) from randomized controlled trials (RCTs) and cohort studies and to identify factors associated with disagreement. METHODS: Systematic reviews were published in the 13 medical journals with the highest impact factor identified through a MEDLINE search. BoE-pairs from RCTs and cohort studies with the same medical research question were included. We rated the similarity of PI/ECO (Population, Intervention/Exposure, Comparison, Outcome) between BoE from RCTs and cohort studies. The agreement of effect estimates across BoE was analyzed by pooling ratio of ratios (RoR) for binary outcomes and difference of mean differences for continuous outcomes. We performed subgroup analyses to explore factors associated with disagreements. RESULTS: One hundred twenty-nine BoE pairs from 64 systematic reviews were included. PI/ECO-similarity degree was moderate: two BoE pairs were rated as "more or less identical"; 90 were rated as "similar but not identical" and 37 as only "broadly similar". For binary outcomes, the pooled RoR was 1.04 (95% CI 0.97-1.11) with considerable statistical heterogeneity. For continuous outcomes, differences were small. In subgroup analyses, degree of PI/ECO-similarity, type of intervention, and type of outcome, the pooled RoR indicated that on average, differences between both BoE were small. Subgroup analysis by degree of PI/ECO-similarity revealed high statistical heterogeneity and wide prediction intervals across PI/ECO-dissimilar BoE pairs. CONCLUSIONS: On average, the pooled effect estimates between RCTs and cohort studies did not differ. Statistical heterogeneity and wide prediction intervals were mainly driven by PI/ECO-dissimilarities (i.e., clinical heterogeneity) and cohort studies. The potential influence of risk of bias and certainty of the evidence on differences of effect estimates between RCTs and cohort studies needs to be explored in upcoming meta-epidemiological studies.