| 1. |
- Berry, Sarah E., et al.
(author)
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Human postprandial responses to food and potential for precision nutrition
- 2020
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26:6, s. 964-973
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Journal article (peer-reviewed)abstract
- Metabolic responses to food influence risk of cardiometabolic disease, but large-scale high-resolution studies are lacking. We recruited n = 1,002 twins and unrelated healthy adults in the United Kingdom to the PREDICT 1 study and assessed postprandial metabolic responses in a clinical setting and at home. We observed large inter-individual variability (as measured by the population coefficient of variation (s.d./mean, %)) in postprandial responses of blood triglyceride (103%), glucose (68%) and insulin (59%) following identical meals. Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake. These findings may be informative for developing personalized diet strategies. The ClinicalTrials.gov registration identifier is NCT03479866.
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| 2. |
- Fabritz, Larissa, et al.
(author)
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Dynamic risk assessment to improve quality of care in patients with atrial fibrillation : the 7th AFNET/EHRA Consensus Conference
- 2021
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In: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:3, s. 329-344
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Journal article (peer-reviewed)abstract
- AimsThe risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.Methods and resultsThis article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.ConclusionThe remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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| 3. |
- Franks, Paul W., et al.
(author)
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Gene-lifestyle interplay in type 2 diabetes
- 2018
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In: Current Opinion in Genetics and Development. - : CURRENT BIOLOGY LTD. - 0959-437X .- 1879-0380. ; 50, s. 35-40
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Research review (peer-reviewed)abstract
- Type 2 diabetes (T2D) is widespread, affecting the health of hundreds of millions worldwide. The disease results from the complex interplay of lifestyle factors acting on a backdrop of inherited DNA risk variants. Detecting and understanding biomarkers, whether genotypes or other downstream biological features that dictate a person's phenotypic response to different lifestyle exposures, may have tremendous utility in the prevention of T2D. Here, we explore (i) evidence of how human genetic adaptation to diverse local environments might interact with lifestyle factors in T2D, (ii) the key challenges facing the research area of gene x lifestyle interactions in T2D, and (iii) the solutions that might be pursued in future studies. Overall, many preliminary examples of such interactions exist, but none is sufficient to have a major impact on clinical decision making. Future studies, integrating genetics and other biological markers into regulatory networks, are likely to be necessary to facilitate the integration of genomics into lifestyle medicine in T2D.
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| 4. |
- Gutierrez-Gutierrez, Belen, et al.
(author)
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Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients
- 2021
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In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:11
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Journal article (peer-reviewed)abstract
- There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.
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| 5. |
- Lim, Siew S, et al.
(author)
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Reporting guidelines for precision medicine research of clinical relevance : the BePRECISE checklist
- 2024
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In: Nature Medicine. - 1546-170X. ; 30:7, s. 1874-1881
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Research review (peer-reviewed)abstract
- Precision medicine should aspire to reduce error and improve accuracy in medical and health recommendations by comparison with contemporary practice, while maintaining safety and cost-effectiveness. The etiology, clinical manifestation and prognosis of diseases such as obesity, diabetes, cardiovascular disease, kidney disease and fatty liver disease are heterogeneous. Without standardized reporting, this heterogeneity, combined with the diversity of research tools used in precision medicine studies, makes comparisons across studies and implementation of the findings challenging. Specific recommendations for reporting precision medicine research do not currently exist. The BePRECISE (Better Precision-data Reporting of Evidence from Clinical Intervention Studies & Epidemiology) consortium, comprising 23 experts in precision medicine, cardiometabolic diseases, statistics, editorial and lived experience, conducted a scoping review and participated in a modified Delphi and nominal group technique process to develop guidelines for reporting precision medicine research. The BePRECISE checklist comprises 23 items organized into 5 sections that align with typical sections of a scientific publication. A specific section about health equity serves to encourage precision medicine research to be inclusive of individuals and communities that are traditionally under-represented in clinical research and/or underserved by health systems. Adoption of BePRECISE by investigators, reviewers and editors will facilitate and accelerate equitable clinical implementation of precision medicine.
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| 6. |
- Louca, Panayiotis, et al.
(author)
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Modest effects of dietary supplements during the COVID-19 pandemic : Insights from 445 850 users of the COVID-19 Symptom Study app
- 2021
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In: BMJ Nutrition, Prevention and Health. - : BMJ. - 2516-5542. ; 4:1, s. 149-157
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Journal article (peer-reviewed)abstract
- Objectives Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. Design App-based community survey. Setting 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373). Main exposure Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020. Main outcome measures SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020. Results In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Conclusion In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.
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| 7. |
- Mazidi, Mohsen, et al.
(author)
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Diet and lifestyle behaviour disruption related to the pandemic was varied and bidirectional among US and UK adults participating in the ZOE COVID Study
- 2021
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In: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 2:12, s. 957-969
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Journal article (peer-reviewed)abstract
- Evidence of the impact of the COVID-19 pandemic on health behaviours in the general population is limited. In this retrospective longitudinal study including UK and US participants, we collected diet and lifestyle data pre-pandemic (896,286) and peri-pandemic (291,871) using a mobile health app, and we computed a bidirectional health behaviour disruption index. Disruption of health behaviour was higher in younger, female and socio-economically deprived participants. Loss in body weight was greater in highly disrupted individuals than in those with low disruption. There were large inter-individual changes observed in 46 health and diet behaviours measured peri-pandemic compared with pre-pandemic, but no mean change in the total population. Individuals most adherent to less healthy pre-pandemic health behaviours improved their diet quality and weight compared with those reporting healthier pre-pandemic behaviours, irrespective of relative deprivation; therefore, for a proportion of the population, the pandemic may have provided an impetus to improve health behaviours. Public policies to tackle health inequalities widened by the pandemic should continue to prioritize diet and physical activity for all, as well as more targeted approaches to support younger females and those living in economically deprived areas.
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| 8. |
- Merino, Jordi, et al.
(author)
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Diet quality and risk and severity of COVID-19 : a prospective cohort study
- 2021
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:11, s. 2096-2104
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation. DESIGN: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively. RESULTS: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation. CONCLUSIONS: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.
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| 9. |
- Merino, Jordi, et al.
(author)
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Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium
- 2019
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 24:12, s. 1920-1932
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Journal article (peer-reviewed)abstract
- Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
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| 10. |
- Merino, Jordi, et al.
(author)
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Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors
- 2020
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 69:1, s. 112-120
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Journal article (peer-reviewed)abstract
- Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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