Age, Multiple Chronic Conditions, and COVID-19: A literature review

BACKGROUND: Various patient demographic and clinical characteristics have been associated with poor outcomes for individuals with coronavirus disease 2019 (COVID-19). To describe the importance of age and chronic conditions in predicting COVID-19 related outcomes. METHODS: Search strategies were conducted in PubMed/MEDLINE. Daily alerts were created. RESULTS: A total of 28 studies met our inclusion criteria. Studies varied broadly in sample size (n=21 to more than 17,000,000). Participants mean age ranged from 48 years to 80 years and the proportion of male participants ranged from 44%-82%. The most prevalent underlying conditions in patients with COVID-19 were hypertension (range: 15% - 69%), diabetes (8% - 40%), cardiovascular disease (4% - 61%), chronic pulmonary disease (1% - 33%), and chronic kidney disease (range 1% - 48%). These conditions were each associated with an increased in-hospital case fatality rate ranging from 1% to 56%. Overall, older adults have a substantially higher case fatality rate (CFR) as compared with younger individuals affected by COVID-19 (42% for those \u3c 65 vs 65% \u3e 65 years ). Only one study examined the association of chronic conditions and the risk of dying across different age groups; their findings suggested similar trends of increased risk in those \u3c 65 and those \u3e 65 years as compared to those without these conditions. CONCLUSIONS: There has been a traditional, single condition approach to consideration of how chronic conditions and advancing age relate to COVID-19 outcomes. A more complete picture of the impact of burden of multimorbidity and advancing patient age is needed

Multimodel Ensembles of Wheat Growth: More Models are Better than One

Crop models of crop growth are increasingly used to quantify the impact of global changes due to climate or crop management. Therefore, accuracy of simulation results is a major concern. Studies with ensembles of crop models can give valuable information about model accuracy and uncertainty, but such studies are difficult to organize and have only recently begun. We report on the largest ensemble study to date, of 27 wheat models tested in four contrasting locations for their accuracy in simulating multiple crop growth and yield variables. The relative error averaged over models was 24-38% for the different end-of-season variables including grain yield (GY) and grain protein concentration (GPC). There was little relation between error of a model for GY or GPC and error for in-season variables. Thus, most models did not arrive at accurate simulations of GY and GPC by accurately simulating preceding growth dynamics. Ensemble simulations, taking either the mean (e-mean) or median (e-median) of simulated values, gave better estimates than any individual model when all variables were considered. Compared to individual models, e-median ranked first in simulating measured GY and third in GPC. The error of e-mean and e-median declined with an increasing number of ensemble members, with little decrease beyond 10 models. We conclude that multimodel ensembles can be used to create new estimators with improved accuracy and consistency in simulating growth dynamics. We argue that these results are applicable to other crop species, and hypothesize that they apply more generally to ecological system models

Heterogeneous Parameter Uncertainty and the Timing of Investment During Crisis

We present a model in which investors observe the same macroeconomic data but have varying levels of information about the parameters that determine the distribution of the expected returns on investment. During a crisis that increases macroeconomic uncertainty and reduces asset prices, the threshold required return that triggers investment is lower for an informed investor than for an uninformed investor. Simulation of the model suggests that when macroeconomic uncertainty is high investment may increase, is mostly by informed investors, and as time goes on is progressively more by investors who were initially relatively uninformed about model parameters. For over 10,000 instances of firm-level FDI data for Korea from 1996 to 2001, regression results are consistent with the hypothesis that disproportionably more FDI is made by more informed investors during a period of high macroeconomic uncertainty

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Venous thromboembolism in the elderly. A community-based perspective.

While the magnitude of venous thromboembolism (VTE) increases dramatically with advancing age, relatively little is known about the contemporary management of VTE in the elderly and the impact of age on associated short- and long-term outcomes. The objectives of this population-based study were to compare the clinical characteristics, treatment practices, and outcomes of subjects \u3e or = 65 years with VTE to those of younger patients. The medical records of residents of the Worcester (MA, USA) metropolitan area with ICD-9 codes consistent with VTE during 1999, 2001, and 2003 were independently validated and reviewed by trained data abstractors. Information about patients\u27 demographic and clinical characteristics, hospital management practices, and hospital and long-term outcomes was collected. There were a total of 1,897 validated events of VTE - 1,048 (55%) occurred in patients \u3e or = 65 years of age. Patients \u3e or = 65 years were less likely to have unprovoked VTE than younger patients. They were less likely to receive parenteral anticoagulation or warfarin as acute treatment. Rates of recurrent VTE did not differ significantly between patients 65 years of age or older compared to younger patients but the adjusted rates of major bleeding were increased approximately two-fold in older patients. In conclusion, advancing age is not a predictor of recurrent VTE but is associated with a significant increase in major bleeding episodes. Physicians treating elderly patients with VTE should continue to base their decisions on clinical characteristics previously shown to impact the risk of recurrent VTE. These decisions must be tempered by our observation that major bleeding occurs frequently in these patients

The Impact of Clinical Trials on the Use of Medications for Acute Myocardial Infarction

Background: The impact of clinical trials on medical practice remains controversial, in part because of weak study designs and nonrepresentative study samples. Objective: To assess changes in trends in medication use in the setting of acute myocardial infarction (AMI) before and after publication of two large clinical trials: the Second International Study of Infarct Survival (ISIS-2) trial that supported the use of aspirin after AMI and the Multicenter Diltiazem Postinfarction Trial that reported no overall benefit from the use of calcium antagonists after AMI. Methods: Study patients consisted of 2114 patients hospitalized with AMI in 16 hospitals in metropolitan Worcester, Mass, during 1986, 1988, and 1990. Data were obtained from medical records. We used multivariable logistic regression models to examine the rate of change in the use of selected medications before and after trial publication, controlling for medical history, characteristics and complications of AMI, medications taken, and procedures performed during hospitalization. The dependent variable was receipt of the specific medication under investigation. Results: Before publication of ISIS-2, 26% of patients with AMI received aspirin while hospitalized compared with 66% after its publication. However, in-hospital aspirin use began to rise before ISIS-2 with an immediate increase in the level of use occurring after trial publication but with no significant change in the rate of increase. Before publication of the Multicenter Diltiazem Postinfarction Trial, 57% of patients with AMI were new recipients of calcium antagonists compared with 51% after trial publication. The decrease in calcium antagonist use began after trial publication (odds ratio, 0.79 per 6-month period; 95% confidence interval, 0.71 to 0.88). Conclusions: The published results of large trials of cardiovascular therapies have had variable impact on medication use. Efforts to assess the effects of publication of new scientific information on medical care need to consider prior trends in treatment patterns and the varying contexts of medical care. They should consider both direct and indirect routes of influence.(Arch Intern Med. 1996;156:54-60

The impact of clinical trials on the use of medications for acute myocardial infarction. Results of a community-based study.

BACKGROUND: The impact of clinical trials on medical practice remains controversial, in part because of weak study designs and nonrepresentative study samples. OBJECTIVE: To assess changes in trends in medication use in the setting of acute myocardial infarction (AMI) before and after publication of two large clinical trials: the Second International Study of Infarct Survival (ISIS-2) trial that supported the use of aspirin after AMI and the Multi-center Diltiazem Postinfarction Trial that reported no overall benefit from the use of calcium antagonists after AMI. METHODS: Study patients consisted of 2114 patients hospitalized with AMI in 16 hospitals in metropolitan Worcester, Mass, during 1986, 1988, and 1990. Data were obtained from medical records. We used multivariable logistic regression models to examine the rate of change in the use of selected medications before and after trial publication, controlling for medical history, characteristics and complications of AMI, medications taken, and procedures performed during hospitalization. The dependent variable was receipt of the specific medication under investigation. RESULTS: Before publication of ISIS-2, 26% of patients with AMI received aspirin while hospitalized compared with 66% after its publication. However, in-hospital aspirin use began to rise before ISIS-2 with an immediate increase in the level of use occurring after trial publication but with no significant change in the rate of increase. Before publication of the Multicenter Diltiazem Postinfarction Trial, 57% of patients with AMI were new recipients of calcium antagonists compared with 51% after trial publication. The decrease in calcium antagonist use began after trial publication (odds ratio, 0.79 per 6-month period; 95% confidence interval, 0.71 to 0.88). CONCLUSIONS: The published results of large trials of cardiovascular therapies have had variable impact on medication use. Efforts to assess the effects of publication of new scientific information on medical care need to consider prior trends in treatment patterns and the varying contexts of medical care. They should consider both direct and indirect routes of influence