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Introduction First case of COVID-19 in Colombia was diagnosed on March 6th. Two weeks later, cases have rapidly increased, leading the government to establish some mitigation measures.Objectives The first objective is to estimate and model the number of cases, use of hospital resources and mortality by using different R0 scenarios in a 1-month scenario (from March 18 to April 18, 2020), based on the different isolation measures applied. This work also aims to model, without establishing a time horizon, the same outcomes given the assumption that eventually 70% of the population will be infected.Materials and Methods Data on the number of confirmed cases in the country as of March 18, 2020 (n=93) were taken as the basis for the achievement of the first objective. An initial transmission rate of R0= 2.5 and a factor of 27 for undetected infections per each confirmed case were taken as assumptions for the model. The proportion of patients who may need intensive care or other in-hospital care was based on data from the Imperial College of London. On the other hand, an age-specific mortality rate provided by the Instituto Superiore di Sanita in Italy was used for the second objective.Results Based on the 93 cases reported as of March 18, if no mitigation measures were applied, by April 18, the country would have 613 037 cases. Mitigation measures that reduce R0 by 10% generate a 50% reduction in the number of cases. However, despite halving the number of cases, there would still be a shortfall in the number of beds required and only one in two patients would have access to this resource.Conclusion This model found that the mitigation measures implemented to date by the Colombian government and analyzed in this article are based on sufficient evidence and will help to slow the spread of SARS-CoV-2 in Colombia. Although a time horizon of one month was used for this model, it is plausible to believe that, if the current measures are sustained, the mitigation effect will also be sustained over time.

Sex is a major determinant of cardiometabolic risk. DNA methylation (DNAm), an important epigenetic mechanism that differs between sexes, has been associated with cardiometabolic diseases. Therefore, we aimed to systematically review studies in adults investigating sex-specific associations of DNAm with intermediate cardiometabolic traits and incident cardiovascular disease including stroke, myocardial infarction (MI) and coronary heart disease (CHD). Five bibliographic databases were searched from inception to 15 July 2019. We selected 35 articles (based on 30 unique studies) from 17,023 references identified, with a total of 14,020 participants of European, North American or Asian ancestry. Four studies reported sex differences between global DNAm and blood lipid levels and stroke risk. In 25 studies that took a genome wide or candidate gene approach, DNAm at 31 gene sites was associated with sex differences in cardiometabolic diseases. The identified genes were PLA2G7, BCL11A, KDM6A, LIPC, ABCG1, PLTP, CETP, ADD1, CNN1B, HOOK2, GFBP-7,PTPN1, GCK, PTX3, ABCG1, GALNT2, CDKN2B, APOE, CTH, GNASAS, INS, PON1, TCN2, CBS, AMT, KDMA6A, FTO, MAP3K13, CCDC8, MMP-2 and ER-α. Prioritized pathway connectivity analysis associated these genes with biological pathways such as vitamin B12 metabolism, statin pathway, plasma lipoprotein, plasma lipoprotein assembly, remodeling and clearance and cholesterol metabolism. Our findings suggest that DNAm might be a promising molecular strategy for understanding sex differences in the pathophysiology of cardiometabolic diseases and that future studies should investigate the effects of sex on epigenetic mechanisms in cardiometabolic risk. In addition, we emphasize the gap between the translational potential and the clinical utilization of cardiometabolic epigenetics.

Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989–1993, 2000–2001, 2006–2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose–response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose–response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645

BACKGROUND The role of lifestyle physical activity (PA) trajectories in the mortality risk of patients with coronary heart disease (CHD) remains unclear. OBJECTIVES The purpose of this study was to determine the association of longitudinal PA trajectories with all-cause and cardiovascular disease (CVD) mortality in patients with CHD. METHODS Longitudinal cohorts reporting the association of PA trajectories with mortality in patients with CHD were identified in April 2021 by searching 5 databases without language restrictions. Published HRs and 95% CIs were pooled using random effects models and bias assessed by Egger regression. RESULTS A total of 9 prospective cohorts included 33,576 patients. The mean age was 62.5 years. The maximum follow-up was 15.7 years. All of the studies assessed PA through validated questionnaires, and mortality was well documented. Changes in PA defined 4 nominal PA trajectories. Compared with always-inactive patients, the risk of all-cause mortality was 50% lower in those who remained active (HR: 0.50; 95% CI: 0.39-0.63); 45% lower in those who were inactive but became active (HR: 0.55; 95% CI: 0.44-0.7); and 20% lower in those who were active but became inactive (HR: 0.80; 95% CI: 0.64-0.99). Similar results were observed for CVD mortality, except for the category of decreased activity (HR: 0.91; 95% CI: 0.67-1.24). The overall risk of bias was low. No evidence of publication bias was found. Multiple sensitivity analyses provided consistent results. CONCLUSIONS This study illustrates how patients with CHD may benefit by preserving or adopting an active lifestyle. The observation that the benefits of past activity can be weakened or lost if PA is not maintained may be confounded by disease progression.

Background: Diet has been suggested to play a role in determining the age at natural menopause; however, the evidence is inconsistent. Objective: We systematically reviewed and evaluated published research about associations between diet and onset of natural menopause (ONM). Methods: We searched 6 databases (Medline, Embase, Cochrane, PubMed, Web of Science and Google Scholar) through January 21,2021 to identify prospective studies assessing the association between diet and ONM. Two independent reviewers extracted data using a predesigned data-collection form. Pooled hazard risks (HRs) were calculated using random effect models. Results: Of the 6,137 eligible references we reviewed, we included 15 articles in our final analysis. Those 15 articles included 91,554 women out of 298,413 who experienced natural menopause during follow-up. Overall, there were 89 food groups investigated, 38 macronutrients and micronutrients, and 6 dietary patterns. Among the food groups, higher intake of green and yellow vegetables was associated with earlier age of ONM, while high intakes of some dairy products, such as low-fat, skimmed milk, and low intake of alcohol were associated with a later onset. We observed no consistent association between macronutrient and micronutrient intake and ONM. Our results suggests that a vegetarian diet could be associated with early ONM; we did not observe any other consistent effect from other dietary patterns. Limitations included the number of studies, lack of replication studies and the research being of an observational nature; most studies (11/15) were at medium risk of bias. Conclusion: Although some food items were associated with ONM, the overall evidence about associations between diet and ONM remains controversial. Prospero id: CRD42021232087

ObjectiveTo assess the impact of COVID-19 on the palliative care (PC) publication trend in the last 10 years and the collaboration between countries and main topics that were discussed in the papers.MethodsWe used Scopus to identify publications on PC between 2012 and 2021 and publications about PC and COVID-19 between 2020 and 2021. We used VOSviewer to assess the main topics using the keywords from the papers and to assess country collaboration.Results1937 publications resulted. An increase in publications about PC was observed during the pandemic, only partially explained by OVID-19-related publications. Cancer-related PC publications were the ones with the most marked increase. We identified six clusters in the distribution of the keywords: bioethics, cancer, nursing home/telemedicine, public health, caring and PC following the WHO definition. The countries with higher number of publications were the United States and England.ConclusionWe showed an increase in the number of PC publications in the last 2 years that was only partially explained by COVID-19-related publications. Most of the publications increase was due to cancer-related publications, since, during the time of the pandemic, publications on cancer and PC increased markedly, while those on heart failure, lung disease and dementia, remained constant.

This systematic review and meta-analysis investigated the association of diabetes and glycemic control with myocardial fibrosis (MF).MF is associated with an increased risk of heart failure, coronary artery disease, arrhythmias, and death. Diabetes may influence the development of MF, but evidence is inconsistent.The authors searched EMBASE, Medline Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar for observational and interventional studies investigating the association of diabetes, glycemic control, and antidiabetic medication with MF assessed by histology and cardiac magnetic resonance (ie, extracellular volume fraction [ECV%] and TA total of 32 studies (88% exclusively on type 2 diabetes) involving 5,053 participants were included in the systematic review. Meta-analyses showed that diabetes was associated with a higher degree of MF assessed by histological collagen volume fraction (n = 6 studies; mean difference: 5.80; 95% CI: 2.00-9.59) and ECV% (13 studies; mean difference: 2.09; 95% CI: 0.92-3.27), but not by native or postcontrast TDiabetes is associated with higher degree of MF assessed by histology and ECV% but not by T

To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs—increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal “break” when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R0) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a “schedule” of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally. Electronic supplementary material The online version of this article (10.1007/s10654-020-00649-w) contains supplementary material, which is available to authorized users.

Background: Use of implantable cardioverter defibrillators is increasingly common. As patients approach the end of life, it is appropriate to deactivate the shock function. Aim: To assess the prevalence of implantable cardioverter defibrillator reprogramming to deactivate the shock function at the end of life and the prevalence of advance directives among this population. Design: Following a previously established protocol available in PROSPERO, we performed a narrative synthesis of our findings and used the logit transformation method to perform our quantitative synthesis. Data sources: We searched seven bibliographic databases (Embase, Cochrane Central register of controlled Trials, Medline-Ovid, Web-of-Science, Scopus, PsychInfo, and CINAHL) and additional sources until April 2019. Results: Of the references we identified, 14 were included. We found a pooled prevalence of implantable cardioverter defibrillator reprogramming at the end of life of 28% (95% confidence interval, 22%–36%) with higher reprogramming rates after the recommendations for managing the device at the end of life were published. Among patients with advance directives, the pooled prevalence of advance directives that explicitly mentioned the device was 1% (95% confidence interval, 1%–3%). Conclusions: The prevalence of implantable cardioverter defibrillator reprogramming and advance directives that explicitly mentioned the device was very low. Study data suggested reprogramming decisions were made very late, after the patient experienced multiple shocks. Patient suffering could be ameliorated if physicians and other healthcare professionals adhere to clinical guidelines for the good management of the device at the end of life and include deactivating the shock function in the discussion that leads to the advance directive.

ObjectiveThe Surprise Question (SQ) is a prognostic screening tool used to identify patients with limited life expectancy. We assessed the SQ’s performance predicting 1-year mortality among patients in ambulatory heart failure (HF) clinics. We determined that the SQ’s performance changes according to sex and other demographic (age) and clinical characteristics, mainly left ventricular ejection fraction (LVEF) and the New York Heart Association (NYHA) functional classifications.MethodsWe conducted a prospective cohort study in two HF clinics. To assess the performance of the SQ in predicting 1-year mortality, we calculated the sensitivity, specificity, positive and negative likelihood ratios, and the positive and negative predictive values. To illustrate if the results of the SQ changes the probability that a patient dies within 1 year, we created Fagan’s nomograms. We report the results from the overall sample and for subgroups according to sex, age, LVEF and NYHA functional class.ResultsWe observed that the SQ showed a sensitivity of 85% identifying ambulatory patients with HF who are in the last year of life. We determined that the SQ’s performance predicting 1-year mortality was similar among women and men. The SQ performed better for patients aged under 70 years, for patients with reduced or mildly reduced ejection fraction, and for patients NYHA class III/IV.ConclusionsWe consider the tool an easy and fast first step to identify patients with HF who might benefit from an advance care planning discussion or a referral to palliative care due to limited life expectancy.

Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to systematically review studies investigating the association between epigenetic marks (global, candidate-gene or genome-wide methylation of DNA, and histone modifications) and blood pressure or hypertension. Five bibliographic databases were searched until the 7th of December 2018. Of 2984 identified references, 26 articles based on 25 unique studies met our inclusion criteria, which involved a total of 28,382 participants. The five studies that assessed global DNA methylation generally found lower methylation levels with higher systolic blood pressure, diastolic blood pressure, and/or presence of hypertension. Eighteen candidate-gene studies reported, in total, 16 differentially methylated genes, including renin-angiotensin-system-related genes (ACE promoter and AGTR1) and genes involved in sodium homeostasis and extracellular fluid volume maintenance system (NET promoter, SCNN1A, and ADD1). Between the three identified epigenome-wide association studies (EWAS), lower methylation levels of SULF1, EHMT2, and SKOR2 were found in hypertensive patients as compared with normotensive subjects, and lower methylation levels of PHGDH, SLC7A11, and TSPAN2 were associated with higher systolic and diastolic blood pressure. In summary, the most convincing evidence has been reported from candidate-gene studies, which show reproducible epigenetic changes in the interconnected renin-angiotensin and inflammatory systems. Our study highlights gaps in the literature on the role of histone modifications in blood pressure and the need to conduct high-quality studies, in particular, hypothesis-generating studies that may help to elucidate new molecular mechanisms.

Epigenetic mechanisms have been suggested to play a role in the genetic regulation of pathways related to inflammation. Therefore, we aimed to systematically review studies investigating the association between DNA methylation and histone modifications with circulatory inflammation markers in blood. Five bibliographic databases were screened until 21 November of 2017. We included studies conducted on humans that examined the association between epigenetic marks (DNA methylation and/or histone modifications) and a comprehensive list of inflammatory markers. Of the 3,759 identified references, 24 articles were included, involving, 17,399 individuals. There was suggestive evidence for global hypomethylation but better-quality studies in the future have to confirm this. Epigenome-wide association studies (EWAS) (n=7) reported most of the identified differentially methylated genes to be hypomethylated in inflammatory processes. Candidate genes studies reported 18 differentially methylated genes related to several circulatory inflammation markers. There was no overlap in the methylated sites investigated in candidate gene studies and EWAS, except for TMEM49, which was found to be hypomethylated with higher inflammatory markers in both types of studies. The relation between histone modifications and inflammatory markers was assessed by one study only. This review supports an association between epigenetic marks and inflammation, suggesting hypomethylation of the genome. Important gaps in the quality of studies were reported such as inadequate sample size, lack of adjustment for relevant confounders, and failure to replicate the findings. While most of the studies have been focused on C-reactive protein, further efforts should investigate other inflammatory markers.

Phytoestrogens might have advantageous effects on diabetes in women. We performed a systematic review and meta-analysis to determine the effect of phytoestrogens on glucose homeostasis and the risk of type 2 diabetes (T2D) among women. Randomized controlled trials (RCTs) and prospective observational studies that assessed associations of phytoestrogens (supplementation, dietary intake, or biomarkers) with fasting glucose or insulin, homeostatic model assessment of insulin resistance (HOMA-IR), or with the risk of T2D were included. We identified 18 RCTs (n = 1687 individuals) investigating the effect of phytoestrogen supplementation on glucose homeostasis and 9 prospective population-based studies (n = 212,796 individuals) examining the association between phytoestrogen intake and the risk of T2D. Compared with placebo, phytoestrogen supplementation resulted in improvements in fasting glucose and HOMA-IR: the pooled mean differences of changes were -0.12 mmol/L (95% CI: -0.20, -0.03 mmol/L) and -0.24 mmol/L (95% CI: -0.45, -0.03 mmol/L), respectively. Although there was no significant decrease in insulin concentrations with overall phytoestrogen supplementation, the pooled mean difference in changes was -0.99 pmol/L (95% CI: -4.65, 2.68 pmol/L). However, the results of RCTs varied by type of phytoestrogens: soy-derived isoflavones and genistein improved glucose homeostasis, whereas isoflavone mix and daidzein had no effect or were associated with an adverse glycemic profile. Higher dietary phytoestrogen intake was associated with a 10% lower risk of developing T2D in observational studies (pooled RR: 0.90; 95% CI: 0.85, 0.96; for the highest compared with the lowest quantiles). Results were similar when the analyses were restricted to only medium- and high-quality studies. Overall, phytoestrogens may have a positive influence on glycemia and could be used for diabetes prevention in women. However, for some individual types of phytoestrogens, such as mixed isoflavones, caution is needed in recommending their use in women, because their use could lead to an adverse glycemic profile in women.

ObjectiveTo assess the effectiveness of home-based palliative care (HBPC) on reducing hospital visits and whether HBPC lowered health care cost.MethodWe searched six bibliographic databases (Embase (Ovid); Cochrane Central Register of Controlled Trials; Medline (Ovid); PubMed; Web of Science Core Collection; and, CINAHL) until February 2019 and performed a narrative synthesis of our findings.ResultsOf the 1,426 identified references, 21 articles based on 19 unique studies met our inclusion criteria, which involved 92,000 participants. In both oncological and non-oncological patients, HBPC consistently reduced the number of hospital visits and their length, as well as hospitalization costs and overall health care costs. Even though home-treated patients consumed more outpatient resources, a higher saving in the hospital costs counterbalanced this. The reduction in overall health care costs was most noticeable for study periods closer to death, with greater reductions in the last 2 months, last month, and last two weeks of life.Significance of resultsStakeholders should recognize HBPC as an intervention that decreases patient care costs at end of life and therefore health care providers should assess the preferences of patients nearing the end-of-life to identify those who will benefit most from HBPC.