Unacceptable use of substandard metrics in policy decisions which mandate large reductions in animal-source foods

Many recent very influential reports, including those from the Global Burden of Disease (GBD) Risk Factor Collaborators, the EAT-Lancet Commission on Food, Planet, Health, and the Lancet Countdown on Health and Climate Change, have recommended dramatic reductions or total exclusion of animal-source foods, particularly ruminant products (red meat and dairy), from the human diet. They strongly suggest that these dietary shifts will not only benefit planetary health but also human health. However, as detailed in this perspective, there are grounds for considerable concern in regard to the quality and transparency of the input data, the validity of the assumptions, and the appropriateness of the statistical modelling, used in the calculation of the global health estimates, which underpin the claimed human health benefits. The lessor bioavailability of protein and key micronutrients from plant-source foods versus animal-source foods was not adequately recognised nor addressed in any of these reports. Furthermore, assessments of bias and certainty were either limited or absent. Despite many of these errors and limitations being publically acknowledged by the GBD and the EAT-Lancet authors, no corrections have been applied to the published papers. As a consequence, these reports continue to erroneously influence food policy decisions and international dietary guidelines, such as the World Wildlife Fund’s Livewell Diet, and the Nordic Nutrition Recommendations 2023.</p

An online case-based teaching and assessment program on clinical history-taking skills and reasoning using simulated patients in response to the COVID-19 pandemic

Background: The COVID-19 pandemic has created unprecedented challenges for medical students and educators worldwide. Groups 1, 2 and 3 of year 3, semester 2 medical students at the Royal College of Surgeons in Ireland (n = 275) had only completed 2, 5 and 7 weeks, respectively, of their scheduled 10-week clinical medicine and surgery attachments, prior to the Irish shutdown of all in-person non-essential activities, including medical student education. Methods: We developed and delivered an online case-based program, focused on history-taking skills and clinical reasoning, using simulated patients and video technologies. 12 tutorials were delivered over 6 weeks to 35 subgroups of 8 students in line with program learning outcomes. Both simulated patients (n = 36), and tutors (n = 45, from retired clinical professors to newly graduated physicians), were rapidly upskilled in Blackboard Collaborate and Microsoft Teams, and also in the provision of constructive feedback. We evaluated this newly developed program by the following three criteria: student attendance, achieved grades, and student feedback. Results: Attendance at the 12 tutorials was higher amongst group 1 and 2 students (75 and 73%) by comparison with group 3 students (60%) (p = 85% agreed that the online program was interactive and very educational. Conclusions: Use of online video technology, tutors of varied experience, and simulated patients were demonstrated to replicate patient encounters, and to facilitate the development of clinical skills remotely during the COVID-19 pandemic.</p

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Associations and effects of omega-3 polyunsaturated fatty acids on cognitive function and mood in healthy adults: A protocol for a systematic review of observational and interventional studies

Introduction The association between long-chain omega-3 polyunsaturated fatty acids (PUFAs), brain health, cognitive function and mood has been the subject of intensive research. Marine-derived omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid, are highly concentrated in neuronal membranes and affect brain function. Many studies have found that consumption of omega-3 PUFAs is associated with lower risk of cognitive or mood dysfunction. However, other studies have demonstrated no beneficial effects. There appears to be inconsistent findings from both epidemiological and randomised controlled trial (RCT) studies. The aim of this review is to compile the previous literature and establish the efficacy of omega-3 PUFAs in enhancing cognitive performance and mood in healthy adults. Methods and analysis Prospective cohort studies, RCTs, controlled clinical trials, controlled before and after studies, interrupted time series with a minimum of 3 months duration will be eligible for inclusion. Studies on healthy adults over the age of 18, where the intervention/exposure of interest is omega-3 PUFAs will be included. The outcomes of interest are cognition and mood. Studies will be eligible for inclusion if they measure changes in cognitive function or mood, or the risk of developing cognitive or mood disorders using validated tools and assessments. Relevant search terms and keywords will be used to generate a systematic search in Cochrane Library, MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus and the grey literature. Two independent reviewers will screen studies for eligibility. Risk of bias in cohort and non-randomised studies will be assessed using the ROBINS-I tool. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials will be used for RCTs. If there are sufficient data, a meta-analysis will be conducted. Ethics and dissemination This systematic review does not involve primary data collection and therefore formal ethical approval is not required. Results will be disseminated through peer reviewed publications, conference presentations and the popular press. PROSPERO registration number CRD42018080800.</div

Omega-3 index and blood pressure responses to eating foods naturally enriched with omega-3 polyunsaturated fatty acids: a randomized controlled trial

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor—1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world’s population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index < 4%) were more than halved amongst the group that ate both enriched foods. Furthermore, eating the enriched foods resulted in clinically relevant reductions in diastolic blood pressure (− 3.1 mmHg [− 5.8, − 0.3]). We conclude that chicken-meat and eggs, naturally enriched with algae-sourced omega-3-PUFAs, may serve as alternative dietary sources of these essential micronutrients. Unlike many lifestyle interventions, long-term population health benefits do not depend on willingness of individuals to make long-lasting difficult dietary changes, but on the availability of a range of commonly eaten, relatively inexpensive, omega-3-PUFA enriched foods

Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials

Objective: The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods: We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results: Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. Conclusions: Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.</p

Effects of calcium, magnesium, and potassium concentrations on ventricular repolarization in unselected individuals.

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.Results: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.</p