Cox Frailty Model Research Articles

Associations of built environment characteristic using NEWS questionnaires with major cardiovascular diseases and all-cause mortality

Abstract Background The WHO of 2016 reports that cardiovascular diseases (CVDs) represent the leading cause of death in most countries and China has one of the highest prevalence of CVDs[1-2]. In order to reduce the burden of CVD risk factors, environmental interventions have become increasingly recognized as necessary approaches to health promotion and diseases prevention[3]. Pervious evidence mainly from the western countries, examined the effects of built environment on health (i.e. physical activity, mental health, self-reported health scale and CVD risk factors) , while the potential impact on CVDs has not been fully explored[4]. Thus, the aim of this study is to evaluate the longitudinal relationships between perceived built environment attributes using neighborhood environment walkability scale (NEWS) questionnaire and the CVDs in Chinese adults, to explore the different between urban and rural areas, and to provide a logical foundation for both research and policy making. Methods PURE-China is a prospective cohort study, recruiting participants aged 35–70 years from 115 urban and rural communities in 12 provinces of China between 2005 and 2009[5]. Baseline including NEWS information was collected using standardized questionnaires. Participants without any NEWS data and with baseline CVDs were excluded. The primary outcome is the composite of major CVD events and all-cause mortality. The main exposure variables including land use mix-diversity, land use-access, streets connectivity, infrastructure for walking and cycling, aesthetics, safety from traffic, safety from crime, and community satisfaction. Cox frailty model with random intercepts to account for cluster were used to assess the association between total built environment score/ subscales score and the time to occurrence of events. Based and fully-adjusted model were estimated and presented as HR and 95%CI. Interactions and stratified subgroup analysis were also tested. Results A total of 32,534 PURE participants were included with averaged 51 years old and 59.9% females. During a median follow-up period of 11.7 years (IQR 9.4 – 12.2), we documented 3298 (10.2%) new CVD events and 1639 (5.1%) all cause deaths. Table 1 summarizes based models and adjusted models results. For composite outcomes, higher level of land use access (HR, 1.06; 95%CI, 1.01-1.11), aesthetics (HR, 1.07; 95%CI, 1.02-1.12), safety from crime (HR, 1.06; 95%CI, 1.01-1.10), community satisfaction (HR, 1.04; 95%CI, 1.00-1.09), combined BE metrics (HR, 1.05; 95%CI, 1.01-1.10) were associated with a lower risk of composite outcome in adjusted model. For major CVD events more statistically significant differences were observed. Conclusions and Relevance High level of specific BE characteristics were associated with lower risk of all-cause mortality and CVD in China. Our findings may guide policy makers on how to implement BE measures to easing the burden of CVDs and premature deaths.Table 1

COVID-19-Related Outcomes Among Group Home Residents with Serious Mental Illness in Massachusetts in the First Year of the Pandemic.

This study examined COVID-19 infection and hospitalizations among people with serious mental illness who resided in residential care group homes in Massachusetts during the first year of the COVID-19 pandemic. The authors analyzed data on 2261 group home residents and COVID-19 data from the Massachusetts Department of Public Health. Outcomes included positive COVID-19 tests and COVID-19 hospitalizations March 1, 2020-June 30, 2020 (wave 1) and July 1, 2020-March 31, 2021 (wave 2). Associations between hazard of outcomes and resident and group home characteristics were estimated using multi-level Cox frailty models including home- and city-level frailties. Between March 2020 and March 2021, 182 (8%) residents tested positive for COVID-19, and 51 (2%) had a COVID-19 hospitalization. Compared with the Massachusetts population, group home residents had age-adjusted rate ratios of 3.0 (4.86 vs. 1.60 per 100) for COVID infection and 13.5 (1.99 vs. 0.15 per 100) for COVID hospitalizations during wave 1; during wave 2, the rate ratios were 0.5 (4.55 vs. 8.48 per 100) and 1.7 (0.69 vs. 0.40 per 100). In Cox models, residents in homes with more beds, higher staff-to-resident ratios, recent infections among staff and other residents, and in cities with high community transmission risk had greater hazard of COVID-19 infection. Policies and interventions that target group home-specific risks are needed to mitigate adverse communicable disease outcomes in this population.Clinical Trial Registration Number This study provides baseline (i.e., pre-randomization) data from a clinical trial study NCT04726371.

Abstract 13367: Plasma Lipidomic Markers of Diet Quality Are Associated With Risk of Coronary Heart Disease in American Indians

Background: Diet quality can affect lipid profiles and subsequent risk of coronary heart disease (CHD). Identifying lipidomic markers of diet quality is needed to inform the development of biomarkers of diet, and to understand the mechanisms driving the diet-CHD relation. Objective: To identify lipidomic markers of diet quality and examine whether these lipids are associated with incident CHD. Methods: We studied 1,694 American Indians (aged 18-75, 62% women) who were free of CHD and had lipidomic and dietary data at baseline (2001-2003). Participants were followed for development of CHD through 2020 (mean follow-up: 17.8 years; total incident cases of CHD: 147). Information on past year diet was collected using the Block Food Frequency Questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI). Mixed effects linear regression was used to identify individual lipid species associated with AHEI at baseline. Cox frailty model was used to estimate the hazard ratio of each AHEI-related lipid for CHD risk. All models adjusted for age, sex, center, education, BMI, smoking, alcohol drinking, level of physical activity, energy intake, diabetes, hypertension, and use of lipid-lowering drugs. Results: Among 1,542 lipid species measured, 71 lipid species (23 known) were associated with AHEI at FDR<0.05. Of these, 10 lipids (5 known) were associated with incident CHD (Figure 1 ). The 5 known lipids associated with incident CHD were CE(22:5) B, PC(p-14:0/22:1)/PC(o-14:0/22:1), PC(p-38:3)/PC(o-38:4) B, PE(p-18:0/20:4)/PE(o-18:0/20:4), and SM(d36:2) A. On average, per standard deviation increase in the baseline level of these lipids was associated with 17%-23% increased risk of CHD. These AHEI-related lipids are enriched in glycerophospholipid metabolism. Conclusion: We identified lipidomic markers of diet quality in American Indians. Some diet-related lipids are associated with risk of CHD beyond established risk factors.

Modelling time-to-dropout via shared frailty Cox models. A trade-off between accurate and early predictions

ABSTRACT This paper investigates the student dropout phenomenon in a technical Italian university from a time-to-event perspective. Shared frailty Cox time-dependent models are applied to analyse the careers of students enrolled in different engineering programs with the aim of identifying the determinants of student dropout through time, predicting the time to dropout as soon as possible and to observe how the dropout phenomenon varies across time and degree programs. The innovative contributions of this work are methodological and managerial. First, the adoption of shared frailty Cox models with time-varying covariates is relatively new to the student dropout literature and it allows to consider the student career evolution and the heterogeneity across degree programs. Second, understanding the dropout pattern over time and identifying the earliest moment for obtaining its accurate prediction allow policy makers to set timely interventions for students at risk of dropout.

Non-cuffed central venous catheter for unplanned and urgent start haemodialysis in chronic kidney disease: A multi-centre experience from India.

Central Venous Catheter (CVC) is indispensable to unplanned and urgent start haemodialysis in chronic kidney disease (CKD). While cuffed CVC is preferred to non-cuffed CVC for urgent start haemodialysis, patient's clinical condition might warrant immediate insertion of non-cuffed CVC. In the resource poor setting, non-cuffed CVCs might have to be retained longer than guideline recommended limit of 2 weeks. In this multi-centre retrospective observational study, the real-world survival of non-cuffed CVC was assessed among CKD patients who initiated dialysis urgently. CVC survival was assessed by Kaplan-Meier survival estimate. Predictors of premature CVC loss were assessed using multi-level multi-variate Cox frailty model wherein, each centre was provided with a random intercept to account for within-centre correlation of practice patterns. Among 433 non-cuffed CVCs, there were 393 removals out of which 80% were elective and 20% were premature. The median CVC survival was 37 days (95% CI: 35-41). The rate of premature CVC removal was 4.5/1000 CVC-days (95% CI: 3.6-5.6). Mechanical complications followed by central line associated blood stream infection (CLABSI) were the most common reasons for premature removal. Rate of CLABSI was 1.7/1000 CVC-days (95% CI: 1.2-2.5). Diabetic CKD significantly increased the hazard of premature CVC removal (HR 1.91, 95% CI: 1.01-3.63, p = 0.04) while right internal-jugular location decreased the hazard (HR 0.22, 95% CI: 0.13-0.38, p < 0.001). Prolonged retention of non-cuffed CVC (median 37 days) is common in resource-poor setting. It is worrisome and calls for pre-emptive access creation.

Factors Influencing Hemodialysis Patients Survival Using Frailty Models

Abstract Background and objection: Hemodialysis is the most common renal replacement therapy in patients with End Stage Renal Disease (ESRD). This study investigated the 5-year survival rate of hemodialysis patients admitted to Imam Khomeini and Fatima Zahra Hospitals in Sari. Materials &amp; Methods: This study was performed on 335 patients on hemodialysis referring to Imam Khomeini and Fatima Zahra Hospitals from November 2008 to November 2013. To investigate the factors influencing the patients' survival rate, we used Cox model and Frailty model and compared these models efficiency, we also applied the Akaikie information criterion and the residuals review. All calculations have been performed with SPSS version 20 &amp; STATA version 8 and the significance level was 0.05. Findings: The results of this study showed that applying the Kaplan– Meier method to determine one, three and five year’s survival rates for hemodialysis patients were 74.9%, 53.2% and 20.4%, respectively. The mean survival time was 37.241 months. In the final model, in multivariate analysis of the gamma frailty model, the variables as age, education, marital status, diabetes, Kidney stone &amp; obstructions, the clinic, the mean serum albumin and urea have been identified as the most important predictors in hemodialysis patients' survival (p &lt; 0.05). Conclusion: According to the results of the frailty model fitness, the hemodialysis patients having the same explanatory variables also have different risk of death. Giving the Akaikie information criterion and the residuals review, the Weibull model with gamma frailty is more efficient than the Cox model and it has good fitness to the data.

Combined Evaluation of Arterial Stiffness and Blood Pressure Promotes Risk Stratification of Peripheral Arterial Disease

BackgroundPrevious studies have reported the separate association of arterial stiffness (AS) and blood pressure with peripheral arterial disease (PAD). ObjectivesThe aim of this study was to investigate the risk stratification capacity of AS on incident PAD beyond blood pressure status. MethodsA total of 8,960 participants from Beijing Health Management Cohort were enrolled at the first health visit between 2008 and 2018 and then followed until the incidence of PAD or 2019. Elevated AS was defined as brachial-ankle pulse-wave velocity (baPWV) >1,400 cm/s, including moderate stiffness (1,400 ≤ baPWV <1,800 cm/s) and severe stiffness (baPWV ≥1,800 cm/s). PAD was defined as ankle-brachial index <0.9. A frailty Cox model was used to calculate the HR, integrated discrimination improvement, and net reclassification improvement. ResultsDuring follow-up, 225 participants (2.5%) developed PAD. After adjusting for confounding factors, the highest risk for PAD was observed in the group with elevated AS and blood pressure (HR: 2.253; 95% CI: 1.472-3.448). Among participants with ideal blood pressure and those with well-controlled hypertension, PAD risk was still significant for severe AS. The results remained consistent in multiple sensitivity analyses. In addition, baPWV significantly improved the predictive capacity for PAD risk beyond systolic and diastolic blood pressures (integrated discrimination improvement 0.020 and 0.190, net reclassification improvement 0.037 and 0.303). ConclusionsThis study suggests the clinical importance of combined evaluation and control of AS and blood pressure for the risk stratification and prevention of PAD.

The association of energy and macronutrient intake at breakfast and cardiovascular disease in Chinese adults: From a 14-year follow-up cohort study.

We aimed to examine the associations between energy and macronutrient intakes at breakfast and the incidence of cardiovascular events among Chinese adults. There were 12,937 participants from the China Health and Nutrition Survey who met the study criteria and completed six rounds of questionnaires in 1997, 2000, 2004, 2006, 2009, and 2011. Combined weighing methods with 24-h dietary recall were used to measure dietary intake throughout the day. Intakes of macronutrients at breakfast were calculated using energy provided by nutrients as a percentage of breakfast energy. We calculated hazard ratios using a multivariable Cox frailty model with random intercepts to account for household clustering. During follow-up, we documented 453 (3.6 per 1,000 person-years) major cardiovascular events, 195 (1.5 per 1,000 person-years) myocardial infarctions, and 293 (2.3 per 1,000 person-years) strokes. In Chinese adults, more breakfast carbohydrates or less proteins intake was associated with the reduced risk of cardiovascular diseases. Especially for women, higher intake of breakfast carbohydrates was associated with a lower risk of major cardiovascular events (quintile 5 vs. quintile 1, HR 0.47 [95%CI 0.30-0.74]; p trend = 0.0008) and stroke (quintile 5 vs. quintile 1, HR 0.48 [95%CI 0.26-0.88]; p trend = 0.0006). Higher intake of breakfast proteins was associated with a higher risk of major cardiovascular events (quintile 5 vs. quintile 1, HR 1.77 [95%CI 1.12-2.79]; p trend = 0.1162), myocardial infarction (quintile 5 vs. quintile 1, HR 2.49 [95%CI 1.21-5.11]; p trend = 0.2641). There was a significant association between breakfast fat intake and cardiovascular diseases in the adult population, but less significant correlation was found in Chinese men or women. Breakfast fat intake was positively associated with the risk of major cardiovascular events (quintile 5 vs. quintile 1, HR 1.74 [95%CI 1.27-2.36]; p trend = 0.0070), myocardial infarction (quintile 5 vs. quintile 1, HR 2.03 [95%CI 1.23-3.37]; p trend = 0.0168), and stroke (quintile 5 vs. quintile 1, HR 1.64 [95%CI 1.12-2.41]; p trend = 0.0732). There was a significant reduction in major cardiovascular events and stroke when breakfast energy intake was moderated, even if the independence of skipping breakfast. High carbohydrate intake and low protein and fat intake at breakfast may contribute to cardiovascular health while maintaining a moderate energy intake.

Racial disparities in the pharmacological treatment of insomnia: A time-to-event analysis using real-world data

ObjectiveExamine the association between race and time to pharmacologic treatment of insomnia in a large multi-institutional cohort. MethodsRetrospective analysis of electronic medical records from a regional health information exchange. Eligible patients included adults with at least one healthcare visit per year from 2010 to 2019, a new insomnia diagnosis code during the study period, and no prior insomnia diagnosis codes or medications. A Cox frailty model was used to examine the association between race and time to an insomnia medication after diagnosis. ResultsIn total, 9557 patients were analyzed, 7773 (81.3%) of whom where White, 1294 (13.5%) Black, 238 (2.5%) Other, and 252 (2.6%) unknown race. About 6.2% of Black and 8% of Other race patients received an order for a Food and Drug Administration-approved insomnia medication after diagnosis compared with 13.5% of White patients. Black patients were significantly less likely to have an order for a Food and Drug Administration-approved insomnia medication at all time points (adjusted hazard ratio [aHR] range: 0.37-0.73), and patients reporting Other race were less likely to have received an order at 2 (aHR 0.51, 95% confidence interval [CI] 0.28-0.94), 3 (aHR 0.33, 95% CI 0.13-0.79), and 4 years (aHR 0.21, 95% CI 0.06-0.71) of follow-up. Similar results were observed in a sensitivity analysis including off-label medications. ConclusionsPatients belonging to racial minority groups are less likely to be prescribed an insomnia medication than White patients after accounting for sociodemographic and clinical factors. Further research is needed to determine the extent to which patient preferences and physician perceptions affect these prescribing patterns and investigate potential disparities in nonpharmacologic treatment.

Effect of Ivermectin® on survivorship and fertility of Anopheles arabiensis in Ethiopia: an in vitro study

BackgroundInnovative vector control tools are needed to counteract insecticide resistance and residual malaria transmission. One of such innovative methods is an ivermectin (IVM) treatment to reduce vector survival. In this study, a laboratory experiment was conducted to investigate the effect of ivermectin on survivorship, fertility and egg hatchability rate of Anopheles arabiensis in Ethiopia.MethodsAn in vitro experiment was conducted using 3–5 days old An. arabiensis adults from a colony maintained at insectary of Tropical and Infectious Diseases Research Center, Jimma University (laboratory population) and Anopheles mosquitoes reared from larvae collected from natural mosquito breeding sites (wild population). The mosquitoes were allowed to feed on cattle blood treated with different doses of ivermectin (0 ng/ml, 5 ng/ml, 10 ng/ml, 20 ng/ml, 40 ng/ml and 80 ng/ml). During each feeding experiment, the mosquitoes were held in cages and blood-fed using a Hemotek feeder. Mortality and egg production were then recorded daily for up to 9 days. Time to death was analysed by a Cox frailty model with replicate as frailty term and source of mosquito (wild versus laboratory), treatment type (ivermectin vs control) and their interaction as categorical fixed effects. Kaplan Meier curves were plotted separately for wild and laboratory populations for a visual interpretation of mosquito survival as a function of treatment.ResultsBoth mosquito source and treatment had a significant effect on survival (P < 0.001), but their interaction was not significant (P = 0.197). Compared to the controls, the death hazard of An. arabiensis that fed on ivermectin-treated blood was 2.3, 3.5, 6.5, 11.5 and 17.9 times that of the control for the 5 ng/ml, 10 ng/ml, 20 ng/ml, 40 ng/ml, and 80 ng/ml dose, respectively. With respect to the number of hatched larvae, hatched pupae and emerged adults per fed mosquitoes, a significant difference was found between the control and the 5 ng/ml dose group (P < 0.001). The number of hatched larvae and pupae, and emerged adults decreased further for the 10 ng/ml dose group and falls to zero for the higher doses.ConclusionTreating cattle blood with ivermectin reduced mosquito survival, fertility, egg hatchability, larval development and adult emergence of An. arabiensis in all tested concentrations of ivermectin in both the wild and laboratory populations. Thus, ivermectin application in cattle could be used as a supplementary vector control method to tackle residual malaria transmission and ultimately achieve malaria elimination in Ethiopia.

Ultra-processed foods and mortality: analysis from the Prospective Urban and Rural Epidemiology study

BackgroundHigher intake of ultra-processed foods (UPFs) has been associated with increased risk of CVD and mortality in observational studies from Western countries but data from non-Western countries are limited. ObjectivesWe aimed to assess the association between consumption of UPFs and risk of mortality and major CVD in a cohort from multiple world regions. DesignThis analysis includes 138,076 participants without a history of CVD between the ages of 35 and 70 y living on 5 continents, with a median follow-up of 10.2 y. We used country-specific validated food-frequency questionnaires to determine individuals’ food intake. We classified foods and beverages based on the NOVA classification into UPFs. The primary outcome was total mortality (CV and non-CV mortality) and secondary outcomes were incident major cardiovascular events. We calculated hazard ratios using multivariable Cox frailty models and evaluated the association of UPFs with total mortality, CV mortality, non-CV mortality, and major CVD events. ResultsIn this study, 9227 deaths and 7934 major cardiovascular events were recorded during the follow-up period. We found a diet high in UPFs (≥2 servings/d compared with 0 intake) was associated with higher risk of mortality (HR: 1.28; 95% CI: 1.15, 1.42; P-trend < 0.001), CV mortality (HR: 1.17; 95% CI: 0.98, 1.41; P-trend = 0.04), and non-CV mortality (HR: 1.32; 95% CI 1.17, 1.50; P-trend < 0.001). We did not find a significant association between UPF intake and risk of major CVD. ConclusionsA diet with a high intake of UPFs was associated with a higher risk of mortality in a diverse multinational study. Globally, limiting the consumption of UPFs should be encouraged.

Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system

Background: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. Objective: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. Methods: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). Results: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09–0.22) for the waiting group and 0.40 (95% CI 0.32–0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30–0.46) and 0.44 (95% CI 0.37–0.52), respectively. Conclusions: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.

Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study

The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development. We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries. During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality. The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance. Full funding sources are listed at the end of the paper (see Acknowledgments).

Interaction of Depression and Unhealthy Diets on the Risk of Cardiovascular Diseases and All-Cause Mortality in the Chinese Population: A PURE Cohort Substudy.

This study aimed to identify the interaction of depression and diets on cardiovascular diseases (CVD) incident and death in China and key subpopulations. We included 40,925 participants from the Prospective Urban Rural Epidemiology (PURE)-China cohort which recruited participants aged 35-70 years from 45 urban and 70 rural communities. Depression was measured by the adapted Short-Form (CIDI-SF). The unhealthy diet was considered when the score of Alternative Healthy Eating Index was below the lowest tertile. The primary outcome was a composite outcome of incident CVD and all-cause mortality. Cox frailty models were used to examine the associations. During a median follow-up of 11.9 years (IQR: 9.6-12.6 years), depression significantly increased the risk of the composite outcome (HR = 2.00; 95% CI, 1.16-3.27), major CVD (HR = 1.82; 95% CI, 1.48-2.23), and all-cause mortality (HR = 2.21; 95% CI, 1.51-3.24) for the unhealthy diet group, but not for the healthy diet group. The interaction between depression and diet for the composite outcome was statistically significant (RERI = 1.19; 95% CI, 0.66-1.72; AP = 0.42, 95% CI, 0.27-0.61; SI = 3.30, 95% CI, 1.42-7.66; multiplicative-scale = 1.74 95% CI, 1.27-2.39), even in the subgroup and sensitivity analyses. In addition, the intake of vegetable and polyunsaturated fatty acids contributed most to the interaction of diets and depression. Depressive participants should focus on healthy diets, especially vegetables and polyunsaturated fatty acids, to avoid premature death and CVD.

Post-acute sequelae of COVID-19 among hospitalized patients in Estonia: Nationwide matched cohort study.

Post-acute COVID-19 sequelae refers to a variety of health complications involving different organ systems that have been described among individuals after acute phase of illness. Data from unselected population groups with long-time follow up is needed to comprehensively describe the full spectrum of post-acute COVID-19 complications. In this retrospective nationwide cohort study, we used data obtained from electronic health record database. Our primary cohort were adults hospitalized with confirmed COVID-19 and matched (age, sex, Charlson Comorbidity Index) unaffected controls from general population. Individuals included from February 2020 until March 2021 were followed up for 12 months. We estimated risks of all-cause mortality, readmission and incidence of 16 clinical sequelae after acute COVID-19 phase. Using a frailty Cox model, we compared incidences of outcomes in two cohorts. The cohort comprised 3949 patients older than 18 years who were alive 30 days after COVID-19 hospital admission and 15511 controls. Among cases 40.3% developed at least one incident clinical sequelae after the acute phase of SARS-CoV-2 infection, which was two times higher than in general population group. We report substantially higher risk of all-cause mortality (adjusted hazard ratio (aHR) = 2.57 (95%CI 2.23-2.96) and hospital readmission aHR = 1.73 (95%CI 1.58-1.90) among hospitalized COVID-19 patients. We found that the risks for new clinical sequalae were significantly higher in COVID-19 patients than their controls, especially for dementia aHR = 4.50 (95% CI 2.35-8.64), chronic lower respiratory disease aHR = 4.39 (95% CI 3.09-6.22), liver disease aHR 4.20 (95% CI 2.01-8.77) and other (than ischemic) forms of heart diseases aHR = 3.39 (95%CI 2.58-4.44). Our results provide evidence that the post-acute COVID-19 morbidity within the first year after COVID-19 hospitalization is substantial. Risks of all-cause mortality, hospitalisation and majority of clinical sequelae were significantly higher in hospitalized COVID-19 patients than in general population controls and warrant targeted prevention efforts.

Covert Brain Infarction as a Risk Factor for Stroke Recurrence in Patients With Atrial Fibrillation.

We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Survival Evaluation of Hospitalized COVID-19 Patients with Cox Frailty Approach.

The survival cox analysis is becoming more popular in time-to-event data analysis. When there are unobserved /unmeasured individual factors, then the results of this model may not be dependable. Hence, this study aimed to determine the factors associated with Covid-19 patients' survival time with considering frailty factor. This study was conducted at 1 of the hospitals in Iran, so that hospitalized patients with COVID-19 were included. Epidemiological, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. Gamma-frailty Cox model was used to identify the effects of the risk factors. A total of 360 patients with COVID-19 enrolled in the study. The median age was 74 years (IQR 61 - 83), 903 (57·7%) were men, and 661 (42·3%) were women; the mortality rate was 17%. The Cox frailty model showed that there is at least a latent factor in the model (P = 0.005). Age and platelet count were negatively associated with the length of stay, while red blood cell count was positively associated with the length of stay of patients. The Cox frailty model indicates that in addition to age, the frailty factor is a useful predictor of survival in Covid-19 patients.

Methadone Dose, Cannabis Use, and Treatment Retention: Findings From a Community-based Sample of People Who Use Unregulated Drugs.

Lower daily methadone dose is negatively associated with retention in methadone maintenance treatment (MMT). Cannabis use during MMT is common, with many patients reporting its use for opioid withdrawal mitigation. We sought to test whether the association between lower MMT dose and treatment retention differs by concurrent high-frequency cannabis use in a community sample of people on MMT. We obtained data from participants initiating MMT in 2 community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We built multivariable Cox frailty models to estimate the relationships between MMT dose (<90 mg/d vs ≥90 mg/d) and time to treatment discontinuation. We included an interaction term to test whether high-frequency (≥daily) cannabis use modified the measured effect of lower treatment dose on treatment retention. Between December 2005 and December 2018, 829 participants (54.1%) initiated at least 1 MMT episode and were included in the analysis. Lower MMT dose was strongly positively associated with treatment discontinuation regardless of concurrent high-frequency cannabis use (interaction P > 0.05). Structural factors including homelessness and incarceration were significantly and positively associated with treatment discontinuation. Although we previously found the magnitude and strength of the relationship between lower MMT dose and high-frequency unregulated opioid use to be tempered during high-frequency cannabis use periods, this effect measure modification does not appear to translate to time retained in treatment. Cannabis-based interventions to promote retention in MMT are unlikely to produce long-term benefit without addressing external factors that place MMT patients at increased risk of treatment discontinuation.

High-sensitivity C-reactive protein and low-density lipoprotein cholesterol association with incident of cardiovascular events: Isfahan cohort study

BackgroundThere are many studies on high-sensitivity C-reactive protein (hs-CRP) association with cardiovascular disease (CVD); however, just a few studies investigated whether the low-density lipoprotein cholesterol (LDL-C) could participate in hs-CRP prognostic strength. This study aimed to determine the alliance of hs-CRP and LDL-C in different concentrations in occurrence cardiovascular events in the Isfahan Cohort Study (ICS).Methods3277 participants aged 35 and above were included in the current analysis. We evaluated the association of elevated hs-CRP levels (≥ 3 mg/dL) and CVD events including myocardial infarction, ischemic heart disease, stroke, CVD, CVD mortality, and all-cause mortality in those with LDL-C ≥ or < 130 mg/dL Cox frailty models was used to determine possible interactions.ResultsIn both crude and fully adjusted models, there was no significant interaction between LDL-C and hs-CRP levels with the incidence of MI, stroke, CVD mortality, and all-cause death. Neither elevated LDL-C alone nor elevated CRP alone were associated with the risk of all cardiovascular events and all-cause death. However, participants with elevated concentrations of both hs-CRP and LDL-C had a greater risk of ischemic heart disease (IHD) (hazards ratio (HR) 1.44; 95% CI 1.03–2.02) and CVD (HR 1.36; 95% CI 1.01–1.83) than those with low LDL-C and hs-CRP.ConclusionThese results indicate that despite a null association between elevated levels of CRP or LDL-C alone and CVD events, concurrent rise in LDL-C and hs-CRP levels is associated with higher risk of IHD and CVD.

Association of Midday Napping with All-Cause Mortality in Chinese Adults: A 8-Year Nationwide Cohort Study

This study aimed to investigate the longitudinal association of estimated daytime nap duration with all-cause mortality in Chinese adults. We conceived a prospective cohort design using adult survey data of the baseline and four follow-up waves (2010–2019) from China Family Panel Studies. Cox frailty models with random intercepts for surveyed provinces were used to estimate risks of all-cause mortality associated with midday napping. Trend and subgroup analyses were also performed stratified by demographic, regional and behavioral factors. Compared with non-nappers, those who reported a long napping duration (≥60 min/day) had an increased risk of all-cause mortality, while shorter napping (<60 min) showed no association with mortality. We observed significant trends for greater risks of mortality associated with longer nap duration. Long nap-associated higher risk of all-cause mortality was seen in a group of nocturnal sleep duration ≥9 h. We identified stronger associations of long nap with mortality among adults aged over 50 years, those with lower BMI (<24 kg/m2), residents in rural regions and unregular exercisers. Long midday napping is independently associated with higher risks of all-cause mortality in Chinese adults.