Outcomes of care during the last month of life: a systematic review to inform the development of a core outcome set.

BACKGROUND: To date, there is a lack of standardization and consensus on which outcomes are central to assess the care provided to patients in the last month of life. Therefore, we aimed to conduct a systematic review to identify relevant outcomes to inform the development of a core outcome set for the best care for the dying person. METHODS: We conducted a systematic review of outcomes reported in the scientific literature about the care for the dying person in the last month of life. We searched for peer-reviewed studies published before February 2022 in four electronic databases. To categorise the outcomes, we employed the taxonomy developed by the "Core Outcome Measures in Effectiveness Trials" collaboration. RESULTS: Out of the 2,933 articles retrieved, 619 were included for analyses. The majority of studies (71%) were retrospective and with data extracted from chart reviews (71%). We extracted 1,951 outcomes in total, from which, after deletion of repeated outcomes, we identified 256 unique ones. The most frequently assessed outcomes were those related to medication or therapeutic interventions and those to hospital/healthcare use. Outcomes related to psychosocial wellbeing were rarely assessed. The closer to death, the less frequently the outcomes were studied. CONCLUSIONS: Most outcomes were related to medical interventions or to hospital use. Only a few studies focused on other components of integrated care such as psychosocial aspects. It remains to be defined which of these outcomes are fundamental to achieve the best care for the dying.

Impact of type 2 diabetes on life expectancy and role of kidney disease among inpatients with heart failure in Switzerland: an ambispective cohort study.

BACKGROUND: Type 2 diabetes (T2D) is expected to worsen the prognosis of inpatients with heart failure (HF) but the evidence from observational studies is inconsistent. We aimed to compare mortality outcomes and life expectancy among inpatients with HF with or without T2D and explored whether chronic kidney disease (CKD) influenced these associations. METHODS: We collected hospital and civil registry records of consecutive inpatients from a tertiary hospital in Switzerland with a diagnosis of HF from the year 2015 to 2019. We evaluated the association of T2D with mortality risk using Cox regression and adjusted for confounders. RESULTS: Our final cohort consisted of 10,532 patients with HF of whom 27% had T2D. The median age (interquartile range [IQR]) was 75 [68 to 82] and 78 [68 to 86] for the diabetes and non-diabetes groups, respectively. Over a median follow-up [IQR] of 4.5 years [3.3 to 5.6], 5,347 (51%) of patients died. T2D patients had higher risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.14 to 1.29). Compared to control (i.e. no T2D nor CKD), average life expectancy (95% CI) among T2D patients, CKD, or both was shorter by 5.4 months (95% CI 1.1 to 9.7), 9.0 months (95% CI 8.4 to 9.6), or 14.8 months (95% CI 12.4 to 17.2), respectively. No difference by sex or ejection fraction category was observed. CONCLUSIONS: T2D is associated with a significantly higher risk of all-cause mortality and shorter life expectancy compared to those without among middle-aged and elderly inpatients with HF; presence of CKD may further increase these risks.

Compassionate communities: How to assess their benefit? A protocol of a collaborative study between different countries.

Background: Communities and local governments invest in compassionate communities (CCs) a great deal of time, money, effort, and work. However, it is not known whether the CCs are having the effect they are expected to have, so the value of continuing with these initiatives is unknown, and there is a need for a model for evaluating CCs to solve the question. Objectives: To identify a set of core outcomes or benefits that should be measured to assess the impact of the CCs. Design: Multiple-methods study involving three communities, each in a different country (Argentina, Colombia, and Switzerland). Methods and analysis: To identifying the set of core outcomes, which is the first step in developing the CC evaluation model, five phases will follow: online meetings, literature review, fieldwork, Delphi survey, and social transfer. We will involve members of the local communities of Bern, Buenos Aires, and Medellin at three different levels: (1) citizens (e.g. patients, caregivers, and family members), (2) organizations and institutions involved in the program implementation (e.g. health care organizations, churches, non-governmental organizations, and schools), and (3) political and governmental sectors. Ethics: The study will be conducted following existing international regulations and guidance such as the Declaration of Helsinki. The ethics committee of Pallium Latin America and the ethics committee of the canton of Bern considered our application exempt from the need for approval. Ethics approval in Bern and Buenos Aires is in the process of being obtained. The ethics committee of the Pontifical Bolivarian University approved this protocol. Discussion: We expect that this project will help bridge the gap in knowledge regarding the measurable impact of the CCs and enhance more CC development.

Palliative care and COVID-19: a bibliometric analysis.

OBJECTIVE: To 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. METHODS: We 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. RESULTS: 1937 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. CONCLUSION: We 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.

Unmet Needs in Patients With Heart Failure: The Importance of Palliative Care in a Heart Failure Clinic.

Background: There are increasing calls to establish heart failure (HF) clinics due to their effectiveness in the interdisciplinary management of people living with HF. However, although a recommendation exists for palliative care (PC) providers to be part of the interdisciplinary team, few of the established HF clinics include them in their teams. Therefore, in this qualitative study, we aimed to understand the unmet PC needs of patients with HF attending an already established HF clinic. Methods: Secondary qualitative analysis of structured interviews undertaken within a larger study to validate the German version of the Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF). The NAT: PD-HF is a tool that aims to assess unmet needs in patients with HF. The interviews took place between January and March 2020 with patients from the ambulatory HF Clinic of a University Hospital in Switzerland. For this analysis, we transcribed and thematically analyzed the longest and most content-rich interviews until we reached data saturation at 31 participants. The interviews lasted 31 min on average (24-48 min). Results: Participants (n = 31) had a median age of 64 years (IQR 56-77), the majority had reduced ejection fraction, were men, and were classified as having a New York Heart Association functional class II. Participants were in general satisfied with the treatment and information received at the HF clinic. However, they reported several unmet needs. We therefore identified three ambivalences as main themes: (I) "feeling well-informed but missing essential discussions", (II) "although feeling mostly satisfied with the care, remaining with unmet care needs", and (III) "fearing a referral to palliative care but acknowledging its importance". Conclusion: Although patients who are receiving multidisciplinary management in ambulatory HF clinics are generally satisfied with the care received, they remain with unmet needs. These unmet needs, such as the need for advance care planning or the need for timely and tactful end-of-life discussions, can be fulfilled by PC providers. Including personnel trained in PC as part of the multidisciplinary team could help to address patients' needs, thus improving the quality of care and the quality of life of people living with HF.

Diabetes and Myocardial Fibrosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis investigated the association of diabetes and glycemic control with myocardial fibrosis (MF). BACKGROUND: 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. METHODS: 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 T1 time). RESULTS: A 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 T1 time. Higher glycosylated hemoglobin levels were associated with higher degrees of MF. CONCLUSIONS: Diabetes is associated with higher degree of MF assessed by histology and ECV% but not by T1 time. In patients with diabetes, worse glycemic control was associated with higher MF degrees. These findings mostly apply to type 2 diabetes and warrant further investigation into whether these associations are causal and which medications could attenuate MF in patients with diabetes.

Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease.

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.

Dietary factors and onset of natural menopause: A systematic review and meta-analysis.

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.

Prevalence and characteristics of patients with heart failure needing palliative care.

BACKGROUND: Few hospitals and heart failure (HF) clinics offer concurrent palliative care (PC) together with life-prolonging therapies. To know the prevalence of patients in HF clinics needing PC and useful tools to recognize them are the first steps to extending PC in those settings. However, it is still unknown whether tools commonly used to identify patients with HF needing PC can correctly distinguish them. Two systematic reviews found that the NECesidades PALiativas (NECPAL) tool was one of the two most commonly used tools to asses PC needs in HF patients. Therefore, we assessed 1) the prevalence of PC needs in HF clinics according to the NECPAL tool, and 2) the characteristics of the patients identified as having PC; mainly, their quality of life (QoL), symptom burden, and psychosocial problems. METHODS: This cross-sectional study was conducted at two HF clinics in Colombia. We assessed the prevalence of PC in the overall sample and in subgroups according to clinical and demographic variables. We assessed QoL, symptom burden, and psychosocial problems using the 12-Item Short-Form Health Survey (SF-12), the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Edmonton Symptom Assessment System (ESAS). We compared the results of these tools between patients identified as having PC needs (+NECPAL) and patients identified as not having PC needs (-NECPAL). RESULTS: Among the 178 patients, 78 (44%) had PC needs. The prevalence of PC needs was twice as nigh in patients NYHA III/IV as in patients NYHA I/II and almost twice as high in patients older than 70 years as in patients younger than 70 years. Compared to -NECPAL patients, +NECPAL patients had worse QoL, more severe shortness of breath, tiredness, drowsiness, and pain, and more psychosocial problems. CONCLUSION: The prevalence of PC needs in outpatient HF clinics is high and is even higher in older patients and in patients at more advanced NYHA stages. Compared to patients identified as not having PC needs, patients identified as having PC needs have worse QoL, more severe symptoms, and greater psychosocial problems. Including a PC provider in the multidisciplinary team of HF clinics may help to assess and cover these needs.

Validation of the German version of the needs assessment tool: progressive disease-heart failure.

BACKGROUND: The Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF) is a tool created to assess the needs of people living with heart failure and their informal caregivers to assist delivering care in a more comprehensive way that addresses actual needs that are unmet, and to improve quality of life. In this study, we aimed to (1) Translate the tool into German and culturally adapt it. (2) Assess internal consistency, inter-rater reliability, and test-retest reliability of the German NAT: PD-HF. (3) Evaluate whether and how patients and health care personnel understand the tool and its utility. (4) Assess the tool's face validity, applicability, relevance, and acceptability among health care personnel. METHODS: Single-center validation study. The tool was translated from English into German using a forward-backward translation. To assess internal consistency, we used Cronbach´s alpha. To assess inter-rater reliability and test-retest reliability, we used Cohen´s kappa, and to assess validity we used face validity. RESULTS: The translated tool showed good internal consistency. Raters were in substantial agreement on a majority of the questions, and agreement was almost perfect for all the questions in the test-retest analysis. Face validity was rated high by health care personnel. CONCLUSION: The German NAT: PD-HF is a reliable, valid, and internally consistent tool that is well accepted by both patients and health care personnel. However, it is important to keep in mind that effective use of the tool requires training of health care personnel.

The 'Surprise question' in heart failure: a prospective cohort study.

OBJECTIVE: The 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: We 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.

Impact of home-based palliative care on health care costs and hospital use: A systematic review.

OBJECTIVE: To assess the effectiveness of home-based palliative care (HBPC) on reducing hospital visits and whether HBPC lowered health care cost. METHOD: We 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. RESULTS: Of 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 RESULTS: Stakeholders 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.

Unmet device reprogramming needs at the end of life among patients with implantable cardioverter defibrillator: A systematic review and meta-analysis.

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.

Dynamic interventions to control COVID-19 pandemic: a multivariate prediction modelling study comparing 16 worldwide countries.

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.

Sexually dimorphic DNA-methylation in cardiometabolic health: A systematic review.

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.

Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.

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.

Proyecciones de impacto de la pandemia COVID-19 en la población colombiana, según medidas de mitigación: datos preliminares de modelos epidemiológicos para el periodo del 18 de marzo al 18 de abril de 2020 / Impact of the COVID-19 pandemic on the Colombian population according to mitigation measures: preliminary data from epidemiological models for the period March 18 to April 18, 2020

RESUMEN Objetivo Este estudio tiene como primer objetivo: realizar predicciones del curso de la infección en el horizonte temporal desde marzo 18 a abril 18 del 2020, según diferentes medidas de aislamiento aplicadas. Las predicciones incluyen, población total contagiada, mortalidad y necesidad de recursos hospitalarios. Segundo objetivo: modelar la mortalidad y la necesidad de recursos hospitalarios, estratificando por edad el escenario de contagio del 70% de la población. Métodos Para el primer objetivo, nos basamos en el número de casos confirmados en el país hasta marzo 18, 2020 (n=93). Como suposiciones para el modelo, incluimos un índice de contagio R0=2,5 y el índice de casos reales por cada caso confirmado. Para la proporción de pacientes que necesitarían cuidados intensivos u otros cuidados intrahospitalarios, nos basamos en datos aportados por el Imperial College of London. Para el segundo objetivo usamos como tasa de mortalidad por edad, datos aportados por el Instituto Superiore di Sanità en Italia. Resultados Basándonos en los 93 casos reportados al 18 de marzo, si no se aplicase ninguna medida de mitigación, para el 18 de abril el país tendría un total de 613 037 casos. Medidas de mitigación que reduzcan el R0 en un 10%, generan una reducción del 50% del número de casos. Sin embargo, a pesar de reducirse los casos a la mitad, todavía habría un déficit en el número de camas requeridas y sólo uno de cada dos pacientes tendría acceso a dicho recurso. Conclusión En nuestro modelo encontramos que las medidas de mitigación que han sido implementadas hasta la fecha por el gobierno colombiano, se fundamentan en evidencia suficiente para pensar que es posible reducir significativamente el número de casos contagiados y con esto, el número de pacientes que requerirán manejo hospitalario.(AU)

ABSTRACT 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 Sanità 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.(AU)

[Impact of the COVID-19 pandemic on the Colombian population according to mitigation measures. Preliminary data from epidemiological models for the period March 18 to April 18, 2020]. / Proyecciones de impacto de la pandemia COVID-19 en la población colombiana, según medidas de mitigación. Datos preliminares de modelos epidemiológicos para el periodo del 18 de marzo al 18 de abril de 2020.

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 Sanità 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.

Correction to: The role of DNA methylation and histone modifications in blood pressure: a systematic review.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The role of DNA methylation and histone modifications in blood pressure: a systematic review.

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.