Evidence-Based Practice Competencies among Nutrition Professionals and Students: A Systematic Review.

BACKGROUND: Evidence-based practice (EBP) promotes shared decision-making between clinicians and patients. OBJECTIVE: The aim was to determine EBP competencies among nutrition professionals and students reported in the literature. METHODS: We conducted a systematic review by searching Medline, Embase, CINAHL, ERIC, CENTRAL, ProQuest Dissertations and Theses Global, BIOSIS Citation Index, and clinicaltrials.gov up to March 2023. Eligible primary studies had to assess one of the 6 predefined EBP competencies: formulating clinical questions; searching literature for best evidence; assessing studies for methodological quality; effect size; certainty of evidence for effects; and determining the applicability of study results considering patient values and preferences. Two reviewers independently screened articles and extracted data, and results were summarized for each EBP competency. RESULTS: We identified 12 eligible cross-sectional survey studies, comprising 1065 participants, primarily registered dietitians, across 6 countries, with the majority assessed in the United States (n = 470). The reporting quality of the survey studies was poor overall, with 43% of items not reported. Only 1 study (8%) explicitly used an objective questionnaire to assess EBP competencies. In general, the 6 competencies were incompletely defined or reported (e.g., it was unclear what applicability and critical appraisal referred to and what study designs were appraised by the participants). Two core competencies, interpreting effect size and certainty of evidence for effects, were not assessed. CONCLUSIONS: The overall quality of study reports was poor, and the questionnaires were predominantly self-perceived, as opposed to objective assessments. No studies reported on competencies in interpreting effect size or certainty of evidence, competencies essential for optimizing clinical nutrition decision-making. Future surveys should objectively assess core EBP competencies using sensible, specific questionnaires. Furthermore, EBP competencies need to be standardized across dietetic programs to minimize heterogeneity in the training, understanding, evaluation, and application among dietetics practitioners. This study was registered at PROSPERO as CRD42022311916.

Microbiota signatures and mucosal healing in the use of enteral nutrition therapy v. corticosteroids for the treatment of children with Crohn's disease: a systematic review and meta-analysis.

Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN v. CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD. Three RCT (n 76) and sixteen cohort studies (n 1104) compared EEN v. CS. With limited available data (one RCT), the effect on intestinal microbiome indicated a trend towards EEN regarding Shannon diversity. Based on two RCT, EEN achieved higher mucosal healing than CS (risk ratio (RR) 2·36, 95 % CI (1·22, 4·57), low certainty). Compared with CS, patients on EEN were less likely to experience adverse events based on two RCT (RR 0·32, 95 % CI (0·13, 0·80), low certainty). For HRQL, there was a trend in favour of CS based on data from two published abstracts of cohort studies. Based on thirteen cohort studies, EEN achieved higher clinical remission than CS (RR 1·18, 95 % CI (1·02, 1·38), very low certainty). Studies also reported no important differences in relapse and adherence. Compared with CS, EEN may improve mucosal healing with fewer adverse events based on RCT data. While limited data indicate the need for further trials, this is the first systematic review to comprehensively summarise the data on intestinal microbiome, mucosal healing and HRQOL when comparing enteral nutrition and CS in paediatric CD.

Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis.

BACKGROUND: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Cyclooxygenase inhibitors (COX-I) may prevent PDA-related complications. Controversy exists on which COX-I drug is the most effective and has the best safety profile in preterm infants. OBJECTIVES: To compare the effectiveness and safety of prophylactic COX-I drugs and 'no COXI prophylaxis' in preterm infants using a Bayesian network meta-analysis (NMA). SEARCH METHODS: Searches of Cochrane CENTRAL via Wiley, OVID MEDLINE and Embase via Elsevier were conducted on 9 December 2021. We conducted independent searches of clinical trial registries and conference abstracts; and scanned the reference lists of included trials and related systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled preterm or low birth weight infants within the first 72 hours of birth without a prior clinical or echocardiographic diagnosis of PDA and compared prophylactic administration of indomethacin or ibuprofen or acetaminophen versus each other, placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. We used the GRADE NMA approach to assess the certainty of evidence derived from the NMA for the following outcomes: severe intraventricular haemorrhage (IVH), mortality, surgical or interventional PDA closure, necrotizing enterocolitis (NEC), gastrointestinal perforation, chronic lung disease (CLD) and cerebral palsy (CP). MAIN RESULTS: We included 28 RCTs (3999 preterm infants). Nineteen RCTs (n = 2877) compared prophylactic indomethacin versus placebo/no treatment, 7 RCTs (n = 914) compared prophylactic ibuprofen versus placebo/no treatment and 2 RCTs (n = 208) compared prophylactic acetaminophen versus placebo/no treatment. Nine RCTs were judged to have high risk of bias in one or more domains.We identified two ongoing trials on prophylactic acetaminophen. Bayesian random-effects NMA demonstrated that prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; absolute risk difference [ARD] 43 fewer [95% CrI, 65 fewer to 16 fewer] per 1000; median rank 2, 95% CrI 1-3; moderate-certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; ARD 24 fewer [95% CrI, 58 fewer to 16 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and surgical PDA closure (network RR 0.40, 95% CrI 0.14 to 0.66; ARD 52 fewer [95% CrI, 75 fewer to 30 fewer] per 1000; median rank 2, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic indomethacin resulted in trivial difference in NEC (network RR 0.76, 95% CrI 0.35 to 1.2; ARD 16 fewer [95% CrI, 42 fewer to 13 more] per 1000; median rank 2, 95% CrI 1-3; high-certainty), gastrointestinal perforation (network RR 0.92, 95% CrI 0.11 to 3.9; ARD 4 fewer [95% CrI, 42 fewer to 137 more] per 1000; median rank 1, 95% CrI 1-3; moderate-certainty) or CP (network RR 0.97, 95% CrI 0.44 to 2.1; ARD 3 fewer [95% CrI, 62 fewer to 121 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty) and may result in a small increase in CLD (network RR 1.10, 95% CrI 0.93 to 1.3; ARD 36 more [95% CrI, 25 fewer to 108 more] per 1000; median rank 3, 95% CrI 1-3; low-certainty). Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; ARD 39 fewer [95% CrI, 75 fewer to 18 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; ARD 66 fewer [95% CrI, from 82 fewer to 31 fewer] per 1000; median rank 1, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic ibuprofen may result in moderate reduction in mortality (network RR 0.83, 95% CrI 0.57 to 1.2; ARD 27 fewer [95% CrI, from 69 fewer to 32 more] per 1000; median rank 2, 95% CrI 1-4; low-certainty) and leads to trivial difference in NEC (network RR 0.73, 95% CrI 0.31 to 1.4; ARD 18 fewer [95% CrI, from 45 fewer to 26 more] per 1000; median rank 1, 95% CrI 1-3; high-certainty), or CLD (network RR 1.00, 95% CrI 0.83 to 1.3; ARD 0 fewer [95% CrI, from 61 fewer to 108 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty). The evidence is very uncertain on effect of ibuprofen on gastrointestinal perforation (network RR 2.6, 95% CrI 0.42 to 20.0; ARD 76 more [95% CrI, from 27 fewer to 897 more] per 1000; median rank 3, 95% CrI 1-3; very low-certainty). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; ARD 22 more [95% CrI, from 122 fewer to 1000 more] per 1000; median rank 4, 95% CrI 1-4; very low-certainty), mortality (network RR 0.49, 95% CrI 0.16 to 1.4; ARD 82 fewer [95% CrI, from 135 fewer to 64 more] per 1000; median rank 1, 95% CrI 1-4; very low-certainty), or CP (network RR 0.36, 95% CrI 0.01 to 6.3; ARD 70 fewer [95% CrI, from 109 fewer to 583 more] per 1000; median rank 1, 95% CrI 1-3; very low-certainty). In summary, based on ranking statistics, both indomethacin and ibuprofen were equally effective (median ranks 2 respectively) in reducing severe IVH and mortality. Ibuprofen (median rank 1) was more effective than indomethacin in reducing surgical PDA ligation (median rank 2). However, no statistically-significant differences were observed between the COX-I drugs for any of the relevant outcomes. AUTHORS' CONCLUSIONS: Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate-certainty), may result in a small increase in CLD (low-certainty) and results in trivial differences in NEC (high-certainty), gastrointestinal perforation (moderate-certainty) and cerebral palsy (low-certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate-certainty), may result in a moderate reduction in mortality (low-certainty) and trivial differences in CLD (low-certainty) and NEC (high-certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically-relevant outcomes.

Values and preferences influencing willingness to change red and processed meat consumption in response to evidence-based information: a mixed methods study.

OBJECTIVES: (1) to assess the extent to which omnivores are willing to stop or reduce their consumption of red and processed meat in response to evidence-based information regarding the possible reduction of cancer mortality and incidence achieved by dietary modification; (2) to identify sociodemographic categories associated with higher willingness to change meat consumption; (3) to understand the motives facilitating and hindering such a change. DESIGN: During an initial computer-assisted web interview, respondents were presented with scenarios containing the estimates of the absolute risk reduction in overall cancer incidence and mortality tailored to their declared level of red and processed meat consumption. Respondents were asked whether they would stop or reduce their average meat consumption based on the information provided. Their dietary choices were assessed at 6-month follow-up. Additionally, we conducted semi-structured interviews to better understand the rationale for dietary practices and the perception of health information. PARTICIPANTS: The study was conducted among students and staff of 3 universities in Krakow, Poland. RESULTS: Most of the 513 respondents were unwilling to change their consumption habits. We found gender to be a significant predictor of the willingness. Finally, we identified 4 themes reflecting key motives that determined meat consumption preferences: the importance of taste and texture, health consciousness, the habitual nature of cooking, and persistence of omnivorous habits. CONCLUSIONS: When faced with health information about the uncertain reduction in the risk of cancer mortality and incidence, the vast majority of study participants were unwilling to introduce changes in their consumption habits.

Visual Analogue Scale has higher assay sensitivity than WOMAC pain in detecting between-group differences in treatment effects: a meta-epidemiological study.

OBJECTIVE: To compare assay sensitivity of the Visual Analogue Scale (VAS) for global osteoarthritis pain and the Western Ontario and McMaster University (WOMAC) pain subscale, and the associated between-trial heterogeneity in effect sizes (ES). DESIGN: We included trials with placebo, sham or non-intervention control that included at least 100 patients with hip or knee osteoarthritis per arm, reporting both VAS and WOMAC pain scores. ES were calculated as between-group difference in means divided by the pooled standard deviation and compared using a paired t-test. ES and τ2 as a measure of between-trial heterogeneity were combined using random-effects meta-regression with robust variance estimation to account for the correlation of data within trials and meta-analyses. RESULTS: Twenty-eight trials with 44 randomized comparisons were included. In 28 comparisons (64%), ES from VAS favoured the intervention more than those from WOMAC pain (P = 0.003). Twenty-six p-values (59%) were smaller according to VAS (P = 0.008). The 44 comparisons contributed to 12 meta-analyses. Eleven meta-analyses (92%) showed larger benefits of interventions according to VAS, with a combined overall difference in ES of -0.08 (95% CI -0.14 to -0.02). τ2 was similar for VAS and WOMAC pain (difference in τ2, -0.003, 95% CI -0.009 to 0.004). CONCLUSION: The VAS for global pain had slightly higher assay sensitivity at trial and meta-analysis levels than the WOMAC pain subscale without relevant increase in between-trial heterogeneity.

Similarities, reliability and gaps in assessing the quality of conduct of systematic reviews using AMSTAR-2 and ROBIS: systematic survey of nutrition reviews.

BACKGROUND: AMSTAR-2 ('A Measurement Tool to Assess Systematic Reviews, version 2') and ROBIS ('Risk of Bias in Systematic Reviews') are independent instruments used to assess the quality of conduct of systematic reviews/meta-analyses (SR/MAs). The degree of overlap in methodological constructs together with the reliability and any methodological gaps have not been systematically assessed and summarized in the field of nutrition. METHODS: We performed a systematic survey of MEDLINE, EMBASE, and the Cochrane Library for SR/MAs published between January 2010 and November 2018 that examined the effects of any nutritional intervention/exposure for cancer prevention. We followed a systematic review approach including two independent reviewers at each step of the process. For AMSTAR-2 (16 items) and ROBIS (21 items), we assessed the similarities, the inter-rater reliability (IRR) and any methodological limitations of the instruments. Our protocol for the survey was registered in PROSPERO (CRD42019121116). RESULTS: We found 4 similar domain constructs based on 11 comparisons from a total of 12 AMSTAR-2 and 14 ROBIS items. Ten comparisons were considered fully overlapping. Based on Gwet's agreement coefficients, six comparisons provided almost perfect (> 0.8), three substantial (> 0.6), and one a moderate level of agreement (> 0.4). While there is considerable overlap in constructs, AMSTAR-2 uniquely addresses explaining the selection of study designs for inclusion, reporting on excluded studies with justification, sources of funding of primary studies, and reviewers' conflict of interest. By contrast, ROBIS uniquely addresses appropriateness and restrictions within eligibility criteria, reducing risk of error in risk of bias (RoB) assessments, completeness of data extracted for analyses, the inclusion of all necessary studies for analyses, and adherence to predefined analysis plan. CONCLUSIONS: Among the questions on AMSTAR-2 and ROBIS, 70.3% (26/37 items) address the same or similar methodological constructs. While the IRR of these constructs was moderate to perfect, there are unique methodological constructs that each instrument independently addresses. Notably, both instruments do not address the reporting of absolute estimates of effect or the overall certainty of the evidence, items that are crucial for users' wishing to interpret the importance of SR/MA results.

Safety and Efficacy of the Combination of Propofol and Ketamine for Procedural Sedation/Anesthesia in the Pediatric Population: A Systematic Review and Meta-analysis.

BACKGROUND: Drugs such as propofol and ketamine are used alone or in combination to provide sedation for medical procedures in children. The purpose of this systematic review was to compare the safety and effectiveness of propofol and ketamine to other drug regimens. METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Web of Science, and the grey literature (meta-Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar) for randomized controlled studies comparing intravenous propofol and ketamine to any other single or combination drug regimen administered to children undergoing diagnostic or therapeutic procedures. Meta-analyses were performed for primary (hemodynamic and respiratory adverse events) and secondary outcomes using RevMan 5.3. We assessed the risk of bias and the certainty (quality) evidence for all outcomes using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-nine studies were included for analysis. Based on low-to-moderate quality evidence, we concluded that the use of propofol and ketamine may result in a slight-to-small reduction in the risk of hypotension, bradycardia, and apnea, and a slight increase in the risk of tachycardia, hypertension, and other respiratory adverse events, such as cough or laryngospasm. The ratio of propofol to ketamine and comparator drug regimen subgroups effects were important for desaturation and some secondary outcomes. CONCLUSIONS: The use of propofol and ketamine had a minimal effect on the incidence of adverse events and other secondary outcomes. Large-scale studies are required to more accurately estimate adverse event rates and the effects of propofol and ketamine on patient-important outcomes.

Evidence Collection and Evaluation for the Development of Dietary Guidelines and Public Policy on Nutrition.

Dietary guidelines and recommendations, usually developed by government bodies or large authoritative organizations, have major downstream effects on public policy. A growing body of evidence supports the notion that there are serious deficiencies in the methods used to develop dietary guidelines. Such deficiencies include the failure to access or conduct comprehensive systematic reviews, a lack of systematic or rigorous evaluation of the quality of the evidence, a failure to acknowledge the limitations of the evidence base underlying recommendations, and insufficiently stringent management of conflicts of interest. These issues may be addressed by adhering to international standards for guideline development, including adopting systematic review methodology and using rigorous systems to evaluate the certainty of the evidence and to move from evidence to recommendations, of which the GRADE approach (Grading of Recommendations Assessment,Development and Evaluation) is the most rigorous and fully developed. Improving the methods by which dietary guidelines are produced has considerable potential to substantially improve public policy decision-making.

Dietary interventions for multiple sclerosis-related outcomes.

BACKGROUND: Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system. Although the exact pathogenesis remains unknown, the leading theory is that it results from immune system dysregulation. Approved disease-modifying therapy appears to modulate the immune system to improve MS-related outcomes. There is substantial interest in the ability of dietary interventions to influence MS-related outcomes. This is an update of the Cochrane Review 'Dietary interventions for multiple sclerosis' (Farinotti 2003; Farinotti 2007; Farinotti 2012). OBJECTIVES: To assess the effects of dietary interventions (including dietary plans with recommendations for specific whole foods, macronutrients, and natural health products) compared to placebo or another intervention on health outcomes (including MS-related outcomes and serious adverse events) in people with MS. SEARCH METHODS: On 30 May 2019, we searched CENTRAL, MEDLINE, Embase, and Web of Science. We also searched ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (ICTRP), and Networked Digital Library of Theses and Dissertations (NDLTD). We checked reference lists in identified trials and requested information from trial authors to identify any additional published or unpublished data. SELECTION CRITERIA: We included any randomized controlled trial (RCT) or controlled clinical trial (CCT) examining the effect of a dietary intervention versus placebo or another intervention among participants with MS on MS-related outcomes, including relapses, disability progression, and magnetic resonance imaging (MRI) measures. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Planned primary outcomes were number of participants experiencing relapse and change in disability progression, according to a validated disability scale at the last reported follow-up. Secondary outcomes included MRI activity, safety, and patient-reported outcomes. We entered and analysed data in Review Manager 5. MAIN RESULTS: We found 41 full-text articles examining 30 trials following full-text review. Participants were adults with MS, defined by established criteria, presenting to MS clinics in Europe, North America, and the Middle East. Study design varied considerably, although all trials had at least one methodological issue leading to unknown or high risk of bias. Trials examined: supplementation to increase polyunsaturated fatty acids (PUFAs) (11 trials); a variety of antioxidant supplements (10 trials); dietary programmes (3 trials); and other dietary supplements (e.g. acetyl L-carnitine, biotin, creatine, palmitoylethanolamide, probiotic, riboflavin) (6 trials). In three trials comparing PUFAs with monounsaturated fatty acids (MUFAs), the evidence was very uncertain concerning difference in relapses (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.20; 3 studies, 217 participants; 75% in the PUFA group versus 74% in the MUFA group; very low-certainty evidence). Among four trials comparing PUFAs with MUFAs, there may be little to no difference in global impression of deterioration (RR 0.85, 95% CI 0.71 to 1.03; 4 studies, 542 participants; 40% in the PUFA group versus 47% in the MUFA group; low-certainty evidence). In two trials comparing PUFAs with MUFAs (102 participants), there was very low-certainty evidence for change in disability progression. None of the PUFA versus MUFA trials examined MRI outcomes. In one trial comparing PUFAs with MUFAs (40 participants), there were no serious adverse events; based on low-certainty evidence. In two trials comparing different PUFAs (omega-3 versus omega-6), there may be little to no difference in relapses (RR 1.02, 95% CI 0.62 to 1.66; 2 studies, 129 participants; 30% in the omega-3 versus 29% in the omega-6 group; low-certainty evidence). Among three trials comparing omega-3 with omega-6, there may be little to no difference in change in disability progression, measured as mean change in Expanded Disability Status Scale (EDSS) (mean difference (MD) 0.00, 95% CI -0.30 to 0.30; 3 studies, 166 participants; low-certainty evidence). In one trial comparing omega-3 with omega-6, there was likely no difference in global impression of deterioration (RR 0.99, 95% CI 0.51 to 1.91; 1 study, 86 participants; 29% in omega-3 versus 29% in omega-6 group; moderate-certainty evidence). In one trial comparing omega-3 with omega-6 (86 participants), there was likely no difference in number of new T1- weighted gadolinium-enhancing lesions, based on moderate-certainty evidence. In four trials comparing omega-3 with omega-6, there may be little to no difference in serious adverse events (RR 1.12, 95% CI 0.38 to 3.31; 4 studies, 230 participants; 6% in omega-3 versus 5% in omega-6 group; low-certainty evidence). In four trials examining antioxidant supplementation with placebo, there may be little to no difference in relapses (RR 0.98, 95% CI 0.59 to 1.64; 4 studies, 345 participants; 17% in the antioxidant group versus 17% in the placebo group; low-certainty evidence). In six trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning change in disability progression, measured as mean change of EDSS (MD -0.19, 95% CI -0.49 to 0.11; 6 studies, 490 participants; very low-certainty evidence). In two trials examining antioxidant supplementation with placebo, there may be little to no difference in global impression of deterioration (RR 0.99, 95% 0.50 to 1.93; 2 studies, 190 participants; 15% in the antioxidant group versus 15% in the placebo group; low-certainty evidence). In two trials examining antioxidant supplementation with placebo, the evidence was very uncertain concerning difference in gadolinium-enhancing lesions (RR 0.67, 95% CI 0.09 to 4.88; 2 studies, 131 participants; 11% in the antioxidant group versus 16% in the placebo group; very low-certainty evidence). In three trials examining antioxidant supplementation versus placebo, there may be little to no difference in serious adverse events (RR. 0.72, 95% CI 0.17 to 3.08; 3 studies, 222 participants; 3% in the antioxidant group versus 4% in the placebo group; low-certainty evidence). AUTHORS' CONCLUSIONS: There are a variety of controlled trials addressing the effects of dietary interventions for MS with substantial variation in active treatment, comparator, and outcomes of interest. PUFA administration may not differ when compared to alternatives with regards to relapse rate, disability worsening, or overall clinical status in people with MS, but evidence is uncertain. Similarly, at present, there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on MS-related outcomes.

Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear. Purpose: To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults. Data Sources: EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles. Study Selection: Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments. Data Synthesis: Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes. Limitation: Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement. Conclusion: The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Health-Related Values and Preferences Regarding Meat Consumption: A Mixed-Methods Systematic Review.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: A person's meat consumption is often determined by their values and preferences. Purpose: To identify and evaluate evidence addressing health-related values and preferences regarding meat consumption. Data Sources: MEDLINE, EMBASE, Web of Science, Centre for Agriculture and Biosciences Abstracts, International System for Agricultural Science and Technology, and Food Science and Technology Abstracts were searched from inception to July 2018 without language restrictions. Study Selection: Pairs of reviewers independently screened search results and included quantitative and qualitative studies reporting adults' health-related values and preferences regarding meat consumption. Data Extraction: Pairs of reviewers independently extracted data and assessed risk of bias. Data Synthesis: Data were synthesized into narrative form, and summaries were tabulated and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Of 19 172 initial citations, 41 quantitative studies (38 addressed reasons for meat consumption and 5 addressed willingness to reduce meat consumption) and 13 qualitative studies (10 addressed reasons for meat consumption and 4 addressed willingness to reduce meat consumption) were eligible for inclusion. Thirteen studies reported that omnivores enjoy eating meat, 18 reported that these persons consider meat an essential component of a healthy diet, and 7 reported that they believe they lack the skills needed to prepare satisfactory meals without meat. Omnivores are generally unwilling to change their meat consumption. The certainty of evidence was low for both "reasons for meat consumption" and "willingness to reduce meat consumption in the face of undesirable health effects." Limitation: Limited generalizability of findings to lower-income countries, low-certainty evidence for willingness to reduce meat consumption, and limited applicability to specific types of meat (red and processed meat). Conclusion: Low-certainty evidence suggests that omnivores are attached to meat and are unwilling to change this behavior when faced with potentially undesirable health effects. Primary Funding Source: None. (PROSPERO: CRD42018088854).

Effect of Lower Versus Higher Red Meat Intake on Cardiometabolic and Cancer Outcomes: A Systematic Review of Randomized Trials.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Few randomized trials have evaluated the effect of reducing red meat intake on clinically important outcomes. Purpose: To summarize the effect of lower versus higher red meat intake on the incidence of cardiometabolic and cancer outcomes in adults. Data Sources: EMBASE, CENTRAL, CINAHL, Web of Science, and ProQuest from inception to July 2018 and MEDLINE from inception to April 2019, without language restrictions. Study Selection: Randomized trials (published in any language) comparing diets lower in red meat with diets higher in red meat that differed by a gradient of at least 1 serving per week for 6 months or more. Data Extraction: Teams of 2 reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. Data Synthesis: Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality (hazard ratio [HR], 0.99 [95% CI, 0.95 to 1.03]), cardiovascular mortality (HR, 0.98 [CI, 0.91 to 1.06]), and cardiovascular disease (HR, 0.99 [CI, 0.94 to 1.05]). That trial also provided low- to very-low-certainty evidence that diets lower in red meat may have little or no effect on total cancer mortality (HR, 0.95 [CI, 0.89 to 1.01]) and the incidence of cancer, including colorectal cancer (HR, 1.04 [CI, 0.90 to 1.20]) and breast cancer (HR, 0.97 [0.90 to 1.04]). Limitations: There were few trials, most addressing only surrogate outcomes, with heterogeneous comparators and small gradients in red meat consumption between lower versus higher intake groups. Conclusion: Low- to very-low-certainty evidence suggests that diets restricted in red meat may have little or no effect on major cardiometabolic outcomes and cancer mortality and incidence. Primary Funding Source: None (PROSPERO: CRD42017074074).

Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. Purpose: To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. Data Sources: Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. Study Selection: Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. Data Synthesis: Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer. Limitation: Limited causal inferences due to residual confounding in observational studies, risk of bias due to limitations in diet assessment and adjustment for confounders, recall bias in dietary assessment, and insufficient data for planned subgroup analyses. Conclusion: The possible absolute effects of red and processed meat consumption on cancer mortality and incidence are very small, and the certainty of evidence is low to very low. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Patterns of Red and Processed Meat Consumption and Risk for Cardiometabolic and Cancer Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes. Purpose: To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality. Data Sources: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language. Study Selection: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Data Synthesis: Eligible studies that followed patients for 2 to 34 years revealed low- to very-low-certainty evidence that dietary patterns lower in red and processed meat intake result in very small or possibly small decreases in all-cause mortality, cancer mortality and incidence, cardiovascular mortality, nonfatal coronary heart disease, fatal and nonfatal myocardial infarction, and type 2 diabetes. For all-cause, cancer, and cardiovascular mortality and incidence of some types of cancer, the total sample included more than 400 000 patients; for other outcomes, total samples included 4000 to more than 300 000 patients. Limitation: Observational studies are prone to residual confounding, and these studies provide low- or very-low-certainty evidence according to the GRADE criteria. Conclusion: Low- or very-low-certainty evidence suggests that dietary patterns with less red and processed meat intake may result in very small reductions in adverse cardiometabolic and cancer outcomes. Primary Funding Source: None. (PROSPERO: CRD42017074074).

Unprocessed Red Meat and Processed Meat Consumption: Dietary Guideline Recommendations From the Nutritional Recommendations (NutriRECS) Consortium.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: Dietary guideline recommendations require consideration of the certainty in the evidence, the magnitude of potential benefits and harms, and explicit consideration of people's values and preferences. A set of recommendations on red meat and processed meat consumption was developed on the basis of 5 de novo systematic reviews that considered all of these issues. Methods: The recommendations were developed by using the Nutritional Recommendations (NutriRECS) guideline development process, which includes rigorous systematic review methodology, and GRADE methods to rate the certainty of evidence for each outcome and to move from evidence to recommendations. A panel of 14 members, including 3 community members, from 7 countries voted on the final recommendations. Strict criteria limited the conflicts of interest among panel members. Considerations of environmental impact or animal welfare did not bear on the recommendations. Four systematic reviews addressed the health effects associated with red meat and processed meat consumption, and 1 systematic review addressed people's health-related values and preferences regarding meat consumption. Recommendations: The panel suggests that adults continue current unprocessed red meat consumption (weak recommendation, low-certainty evidence). Similarly, the panel suggests adults continue current processed meat consumption (weak recommendation, low-certainty evidence). Primary Funding Source: None. (PROSPERO 2017: CRD42017074074; PROSPERO 2018: CRD42018088854).

Virtual reality simulation training in endoscopy: a Cochrane review and meta-analysis.

BACKGROUND: Endoscopy programs are increasingly integrating simulation training. We conducted a systematic review to determine whether virtual reality (VR) simulation training can supplement and/or replace conventional patient-based endoscopy training for health professional trainees with limited or no prior endoscopic experience. METHODS: We searched medical, educational, and computer literature databases in July 2017 for trials that compared VR simulation training with no training, conventional training, another form of simulation training, or an alternative method of VR training. We screened, abstracted data, and performed quantitative analysis and quality assessment through Cochrane methodology. RESULTS: We included 18 trials with 3817 endoscopic procedures. VR training provided no advantage over no training or conventional training based on the primary outcome of composite score of competency. VR training was advantageous over no training based on independent procedure completion (relative risk [RR] = 1.62, 95 % confidence interval [CI] 1.15 - 2.26, moderate-quality evidence), overall rating of performance (mean difference [MD] 0.45, 95 %CI 0.15 - 0.75, very low-quality evidence), and mucosal visualization (MD 0.60, 95 %CI 0.20 - 1.00, very low-quality evidence). Compared with conventional training, VR training resulted in fewer independent procedure completions (RR = 0.45, 95 %CI 0.27 - 0.74, low-quality evidence). We found no differences between VR training and no training or conventional training for other outcomes. Based on qualitative analysis, we found no significant differences between VR training and other forms of simulation training. VR curricula based in educational theory provided benefit with respect to composite score of competency, compared with unstructured curricula. CONCLUSIONS : VR simulation training is advantageous over no training and can supplement conventional endoscopy training. There is insufficient evidence that simulation training provides benefit over conventional training.

Correction to: Methods for trustworthy nutritional recommendations NutriRECS (Nutritional Recommendations and accessible Evidence summaries Composed of Systematic reviews): a protocol.

Following publication of the original article [1], the authors reported a change in the 'Competing interests' section as described below.

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

BACKGROUND: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. OBJECTIVES: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. SEARCH METHODS: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. SELECTION CRITERIA: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. MAIN RESULTS: Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control.After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation.After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. AUTHORS' CONCLUSIONS: The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.

Biofeedback for treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent condition that currently lacks highly effective therapies for its management. Biofeedback has been proposed as a therapy that may help individuals learn to exert conscious control over sympatho-vagal balance as an indirect method of symptom management. OBJECTIVES: Our primary objective was to assess the efficacy and safety of biofeedback-based interventions for IBS in adults and children. SEARCH METHODS: We searched the Cochrane Inflammatory Bowel Disease (IBD) Group Specialized Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Allied and Complementary Medicine Database (AMED) from inception to 24 July 2019. We also searched reference lists from published trials, trial registries, device manufacturers, conference proceedings, theses, and dissertations. SELECTION CRITERIA: We judged randomized controlled trials to be eligible for inclusion if they met the Association for Applied Psychophysiology and Biofeedback definition of biofeedback, and if they compared a biofeedback intervention to an active, sham, or no-treatment control for the management of IBS. DATA COLLECTION AND ANALYSIS: Two authors independently screened trials for inclusion, extracted data, and assessed risk of bias. Primary outcomes were IBS global or clinical improvement scores and overall quality of life measures. Secondary outcome measures were adverse events, assessments of stool frequency and consistency, changes in abdominal pain, depression, and anxiety. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). For continuous outcomes, we calculated the mean difference (MD) and 95% CI. We used GRADE criteria to assess the overall certainty of the evidence. MAIN RESULTS: We identified eight randomized trials with a total of 300 adult participants for our analysis. We did not identify any trials in children. Four trials assessed thermal biofeedback. One trial assessed rectosigmoidal biofeedback. Two trials assessed heart rate variability biofeedback. Two trials assessed electrocutaneous biofeedback. Comparators were: no treatment (symptom monitoring group; three studies), attention control (pseudomeditation; two studies), relaxation control (one study), counseling (two studies), hypnotherapy (one study), standard therapy (one study), and sham biofeedback (one study). We judged all trials to have a high or unclear risk of bias. Global/Clinical improvement The clinical benefit of biofeedback plus standard therapy compared to standard therapy alone was uncertain (RR 4.20, 95% CI 1.40 to 12.58; 1 study, 20 participants; very low-certainty evidence). The same study also compared biofeedback plus standard therapy to sham biofeedback plus standard therapy. The clinical benefit in the biofeedback group was uncertain (RR 2.33, 95% CI 1.13 to 4.80; 1 study, 20 participants; very low-certainty evidence). The clinical benefit of heart rate biofeedback compared to hypnotherapy was uncertain when measured with the IBS severity scoring system (IBS-SSS) (MD -58.80, 95% CI -109.11 to -8.49; 1 study, 61 participants; low-certainty evidence). Compared to counseling, the effect of heart rate biofeedback was unclear when measured with a composite symptom reduction score (MD 7.03, 95% CI -51.07 to 65.13; 1 study, 29 participants; low-certainty evidence) and when evaluated for clinical response (50% improvement) (RR 1.09, 95% CI 0.48 to 2.45; 1 study, 29 participants; low-certainty evidence). The clinical benefit of thermal biofeedback used in a multi-component psychological intervention (MCPI) compared to no treatment was uncertain when measured with a composite clinical symptom reduction score (MD 30.34, 95% CI 8.47 to 52.21; 3 studies, 101 participants; very low-certainty evidence), and when evaluated as clinical response (50% improvement) (RR 2.12, 95% CI 1.24 to 3.62; 3 studies, 101 participants; very low-certainty evidence). Compared to attention control, the effects of thermal biofeedback within an MCPI were unclear when measured with a composite clinical symptom reduction score (MD 4.02, 95% CI -21.41 to 29.45; 2 studies, 80 participants; very low-certainty evidence) and when evaluated as clinical response (50% improvement) (RR 1.10, 95% CI 0.72 to 1.69, 2 studies, 80 participants; very low-certainty evidence). Quality of life A single trial used overall quality of life as an outcome measure, and reported that both the biofeedback and cognitive therapy groups improved after treatment. The trial did not note any between-group differences, and did not report any outcome data. Adverse events Only one of the eight trials explicitly reported adverse events. This study reported no adverse events in either the biofeedback or cognitive therapy groups (RD 0.00, 95% CI -0.12 to 0.12; 29 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is currently not enough evidence to assess whether biofeedback interventions are effective for controlling symptoms of IBS. Given the positive results reported in small trials to date, biofeedback deserves further study in people with IBS. Future research should include active control groups that use high provider-participant interaction, in an attempt to balance non-specific effects of interventions between groups, and report both commonly used outcome measures (e.g. IBS-SSS) and historical outcome measures (e.g. the composite primary symptom reduction (CPSR) score) to allow for meta-analysis with previous studies. Future studies should be explicit in their reporting of adverse events.

Methods for trustworthy nutritional recommendations NutriRECS (Nutritional Recommendations and accessible Evidence summaries Composed of Systematic reviews): a protocol.

BACKGROUND: Recent systematic reviews and editorials suggest that many organizations that produce nutritional guideline recommendations do not adhere to internationally recognized standards set forth by the Institute of Medicine (IoM), Guidelines International Network (GIN), Appraisal of Guidelines Research and Evaluation (AGREE), and Grading Recommendations, Assessment, Development and Evaluation (GRADE). METHODS: The potential solution is an independent group with content expertise and skilled in the methodology of systematic reviews and practice guidelines to produce trustworthy guideline recommendations, recommendations that are supported by publication in a top tier journal. The BMJ Rapid Recommendations project has recently demonstrated the feasibility and utility of this approach. Here, we are proposing trustworthy nutritional guideline recommendations based on internationally accepted guideline development standards, recommendations that will be informed by rigorous and novel systematic reviews of the benefits and harms associated with nutritional exposures, as well as studies on the values and preferences related to dietary behaviors among members of the international community. DISCUSSION: Adhering to international guideline standards, conducting high quality systematic reviews, and actively assessing the values and preferences of key stakeholders is expected to improve the quality of nutritional guidelines and their relevance to end-users, particularly patients and community members. We will send our work for peer review, and if found acceptable, we will publish our nutritional recommendations in top-tier general medicine journals.