Hazard Of All-cause Mortality Research Articles

All-Cause and Cause-Specific Mortality in Children With Congenital Zika Syndrome in Brazil

Congenital Zika syndrome (CZS) can lead to a range of developmental and neurological issues, which increases the risk of early death. However, the all-cause and cause-specific mortality in children with CZS in the first 5 years of life remain unknown. To compare the hazard of all-cause and cause-specific mortality before age 5 years among children with and without CZS in Brazil. This cohort study used nationwide linked routine data including all children born from January 2015 to December 2018 in Brazil. They were followed-up until age 5 years, death, or December 2020, whichever occurred first. All analysis were conducted in May 2024. Confirmed or probable cases of CZS. All-cause and cause-specific deaths from respiratory, infectious and parasitic, and nervous system diseases were the outcomes. Hazard ratios (HRs), comparing children with and without CZS, for all and cause-specific mortality were estimated using Cox proportional hazard models adjusted for region and year of birth, maternal characteristics (age, education, race and/or ethnicity, and marital status), and sex of the newborn. The analysis was conducted in May 2024. In total, there were 11 387 431 live births (5 832 594 male newborns [51.2%]). Of 3080 children notified as CZS cases, 444 (14.4%) died, including 154 (34.7%) from respiratory diseases, 152 (34.2%) from infectious and parasitic diseases, and 82 (18.5%) from nervous system diseases. Children with CZS were predominantly preterm (596 newborns [20.0%] vs 1 122 378 newborns [10.1%]) and had low birth weight (1095 newborns [35.7%] vs 805 373 newborns [7.1%]), compared with children without CZS. After controlling for confounders, children with CZS were 13.10 (95% CI, 11.86-14.46) times more likely to die in the first 5 years of life compared with those without the syndrome. The cause-specific mortality HRs were 30.28 (95% CI, 25.59-35.83) for respiratory diseases, 28.26 (95% CI, 23.85-33.48) for infectious and parasitic diseases, and 57.11 (95% CI, 45.23-72.11) for nervous system diseases. After excluding newborns who were preterm, low birth weight, and/or small for gestational age, the HRs for all-cause and cause-specific deaths were even higher. In this cohort study, children born with CZS had strikingly higher risk of overall and cause-specific mortality. These findings may support the development of clinical protocols to prevent early mortality and improve survival in these children.

Are associations of adulthood overweight and obesity with all-cause mortality, cardiovascular disease, and obesity-related cancer modified by comparative body weight at age 10 years in the UK Biobank study?

Adults living with overweight or obesity do not represent a single homogenous group in terms of mortality and disease risks. The aim of our study was to evaluate how the associations of adulthood overweight and obesity with mortality and incident disease are modified by (i.e., differ according to) self-reported childhood body weight categories. The sample comprised 191,181 men and 242,806 women aged 40-69 years (in 2006-2010) in the UK Biobank. The outcomes were all-cause mortality, incident cardiovascular disease (CVD), and incident obesity-related cancer. Cox proportional hazards regression models were used to estimate how the associations with the outcomes of adulthood weight status (normal weight, overweight, obesity) differed according to perceived body weight at age 10 years (about average, thinner, plumper). To triangulate results using an approach that better accounts for confounding, analyses were repeated using previously developed and validated polygenic risk scores (PRSs) for childhood body weight and adulthood BMI, categorised into three-tier variables using the same proportions as in the observational variables. In both sexes, adulthood obesity was associated with higher hazards of all outcomes. However, the associations of obesity with all-cause mortality and incident CVD were stronger in adults who reported being thinner at 10 years. For example, obesity was associated with a 1.28 (1.21, 1.35) times higher hazard of all-cause mortality in men who reported being an average weight child, but among men who reported being a thinner child this estimate was 1.63 (1.53, 1.75). The ratio between these two estimates was 1.28 (1.17, 1.40). There was also some evidence that the associations of obesity with all-cause mortality and incident CVD were stronger in adults who reported being plumper at 10 years. In genetic analyses, however, there was no evidence that the association of obesity (according to the adult PRS) with mortality or incident CVD differed according to childhood body size (according to the child PRS). For incident obesity-related cancer, the evidence for effect modification was limited and inconsistent between the observational and genetic analyses. Greater risks for all-cause mortality and incident CVD in adults with obesity who perceive themselves to have been a thinner or plumper than average child may be due to confounding and/or recall bias.

Effects of surgical approach and downstaging in esophageal adenocarcinoma patients treated with neoadjuvant chemotherapy: a 2010-2020 National Cancer Database (NCDB) study.

Neoadjuvant Chemoradiation (nCRT) has been shown to improve survival in patients with Esophageal Adenocarcinoma (EAC). The objective of this study is to assess the patient characteristics associated with tumor downstaging in a large national database. Additionally, we evaluated surgical approach and change in clinical versus pathological staging as predictors of patient survival. Using the 2010-2020 National Cancer Database, we identified 6,400 patients with clinical stage 1B to 4A EAC who received nCRT and underwent esophagectomy. Multivariable logistic models were estimated to evaluate odds of downstaging, and complete downstaging. Multivariable marginal Cox proportional-hazard models were estimated to evaluate all-cause mortality hazard. 3285 (51%) patients downstaged (of which 292 [5% of total] completely downstaged), 2430 (38%) had no change in stage, and 685 (11%) progressed. Generally, higher covariate values such as Clinical T, Clinical N, age, and Charlson-Deyo score were associated with higher odds of downstaging and lower odds of complete downstaging. Downstaging was associated with 31% lower risk of death compared to progression (p < .001) and 17% lower risk of death compared to no change (p < .001). Regarding surgical approach, when compared with open esophagectomy (OE), robotic-assisted minimally invasive esophagectomy (RAMIE) was associated with 17% lower adjusted risk of death (p = .002) while minimally invasive esophagectomy (MIE) was associated with a 10% decrease in adjusted risk of death (p = .009). In patients with EAC who underwent nCRT, pathological downstaging was associated with increased survival compared to no change or progression. Additionally, RAMIE and MIE were associated with lower risk of death compared to OE.

Outcomes of chronic limb-threatening ischemia revascularization in patients with chronic kidney disease in the BEST-CLI trial.

Chronic limb-threatening ischemia (CLTI) in patients with chronic kidney disease (CKD) has a high risk of poor outcomes. We aimed to compare the outcomes of lower extremity revascularization in patients with CLTI stratified by CKD severity in patients enrolled in the prospective, randomized Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial. The BEST-CLI trial dataset was queried to categorize patients into three groups according to CKD stage. Group A includes non-CKD and CKD stages<3; group B includes stage 3 and stage 4 CKD patients; and group C includes stage 5 CKD and dialysis-dependent patients. Furthermore, spline modeling was performed across the range of estimated glomerular filtration rate (eGFR, mL/min/1.73m2) observed in study participants to identify a threshold eGFR that impacted the primary trial outcomes: major adverse limb events (MALEs; defined as above-ankle amputation or major reintervention) or all-cause mortality, by surgical or endovascular revascularization (as-treated analysis). Kaplan-Meier and multivariate Cox regression analyses were used to assess association of CKD risk groups with the outcomes. A total of 1797 patients were included. Group C patients had double the risk of amputation (hazard ratio [HR], 2.13; P< .001), MALE, or all-cause mortality (HR, 2.05; P< .001) and more than triple the risk of all-cause mortality (HR, 3.40; P<.001) compared with group A. In dialysis-dependent patients, endovascular therapy was associated with better survival, but twice the risk of reintervention compared with surgical revascularization. According to spline model analysis, hazard of MALE or all-cause mortality increased sharply at eGFR<30. The hazard ratios for eGFR<30 vs ≥60 were 2.03 (95% confidence interval [CI], 1.68-2.43; P< .001) and 3.46 (95% CI, 2.80-4.27; P< .001) for MALE and mortality, respectively. At eGFR<30, there was no difference in the primary outcome by treatment received (surgical or endovascular revascularization). The progressive nature of renal impairment in patients with CLTI threatens their survival and limb salvage and may reduce the relative benefit of open vs endovascular revascularization seen in the overall BEST-CLI trial population. In dialysis-dependent patients, endovascular therapy was associated with lower mortality but increased reintervention rate.

Associations of blood-based biomarkers of neurodegenerative diseases with mortality, cardio- and cerebrovascular events in persons with chronic coronary syndrome.

In light of growing evidence highlighting interactions between cardiac and brain health, we investigated associations of biomarkers of neurodegenerative diseases with adverse outcomes (all-cause and cardiovascular mortality, major cardiovascular events, and stroke) in persons with chronic coronary syndrome (CCS). We used data from a cohort of persons with CCS for whom major adverse events were recorded over a follow-up of 20 years. We measured biomarkers of neurodegenerative diseases in baseline blood samples, using the Single-Molecule Array Technology on a HD-1 Analyzer. These include biomarkers of neuronal (neurofilament light chain (NfL) (n = 379)) and glial neurodegeneration (glial fibrillary acidic protein (GFAP) (n = 379)), and Alzheimer's disease pathology (phosphorylated tau181 (n = 379), total tau (n = 377), and amyloid β (Aβ40, Aβ42, Aβ42/Aβ40) (n = 377)). We applied Cox-proportional hazards models to evaluate associations of these biomarkers with adverse outcomes, adjusting for covariates and exploring interactions with apolipoprotein E (ApoE) ε4 genotype. Participants with higher NfL levels had increased rates of all-cause and cardiovascular mortality (Hazard ratio per increase by one standard deviation (95 % confidence interval): all-cause mortality: 1.36 (1.10-1.68); cardiovascular mortality: 1.42 (1.05-1.93)). The Aβ40/Aβ42-ratio was linked to incident stroke (0.72 (0.52-1.00)). Associations of GFAP with all-cause mortality and incident stroke were depending on ApoE ε4 genotype. The other biomarkers were not significantly associated with the studied outcomes. In persons with CSS, NfL and the Aβ40/Aβ42-ratio were related to mortality and incident stroke, respectively, whereas associations of GFAP with adverse outcomes varied by ApoE genotype. These biomarkers might play a role in linking aging, cardiovascular and neurodegenerative diseases.

Housing matters: The long-term impact of stable housing on mortality among people with HIV in British Columbia, Canada.

For several decades, British Columbia (BC), Canada, has been experiencing a housing crisis marked by a shortage of safe and affordable housing, which coincides with a severe drug poisoning epidemic in the region. We explore the impact of housing instability on mortality (all-cause, drug-related) among a cohort of people with HIV (PWH) in BC. Data are from the Longitudinal Investigation into Supportive and Ancillary Health Services (LISA) study (n=997). Data from the cross-sectional LISA survey (2007-2010) are linked with administrative health data from Population Data BC and the BC Centre for Excellence in HIV/AIDS Drug Treatment Program (DTP) until March 31, 2020. We used inverse probability of participation weighting (IPPW) to address selection bias, introduced in LISA through oversampling of PWH marginalized by sociostructural inequities. We constructed participation weights using information from the DTP database, which includes all known PWH in BC accessing antiretrovirals via the DTP (including respondents and non-respondents to LISA). We estimated hazards of all-cause and drug-related mortality associated with housing instability using an adjusted, IPPW-weighted Cox proportional hazards model. In this sample, 317 (31.8%) people reported housing instability. Overall, 302 people (30.3%) died from any cause between the completion of the LISA survey until March 31, 2020; of those people, 138 (45.7%) experienced housing instability. Results suggest housing instability is associated with increased hazards of all-cause mortality (adjusted Hazards Ratio (aHR): 1.46; 95% CI: 1.08-1.96). The association between housing instability and hazards for drug-related mortality include a range of values consistent with the null (aHR: 1.67; 95% CI: 0.89-3.13). PWH experiencing housing instability may have greater hazards of all-cause mortality. Our findings add to the literature supporting a need to expand access to safe and affordable housing.

Risk of mortality between warfarin and direct oral anticoagulants: population-based cohort studies

BackgroundDirect oral anticoagulants (DOACs) have been reported to be associated with a higher risk of mortality compared with an older alternative, warfarin using primary care data in the United Kingdom (UK). However, other studies observed contradictory findings. We therefore aimed to investigate the association between mortality and warfarin, compared with DOACs.MethodsWe conducted cohort studies using UK Clinical Practice Research Datalink (CPRD) Aurum and Hong Kong Clinical Data Analysis and Reporting System (CDARS) to identify the association between warfarin and hazard of mortality, compared to DOACs. Individuals with non-valvular atrial fibrillation aged ≥ 18 years who had first anticoagulant therapy (warfarin or DOAC) during 1/1/2011–31/12/2019 were included.ResultsCompared with DOAC use, a lower hazard of all-cause mortality was found in warfarin users (hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.77–0.86) in CPRD; while a higher hazard was observed in warfarin users (HR = 1.31, 95% CI = 1.24–1.39) in CDARS, versus DOAC users. In our exploratory analysis, consistent results were seen in both databases when stratified warfarin users by time in therapeutic range (TTR) using post-baseline measurements: a lower hazard of all-cause mortality in warfarin users with TTR ≥ 65% (CPRD: HR = 0.68, 95% CI = 0.65–0.72; CDARS: HR = 0.86, 95% CI = 0.77–0.96) and increased hazard in warfarin users with TTR < 65% (CPRD: HR = 1.14, 95% CI = 1.05–1.23; CDARS: HR = 1.59, 95% CI = 1.50–1.69), versus DOAC users.ConclusionsThe differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. Notably, this study is unable to establish a causal relationship between warfarin and mortality stratified by TTR, versus DOACs, requiring future studies for further investigation.

Association between serum urate levels and all-cause mortality, cardiovascular and renal outcomes among gout patients in Singapore

ObjectivesWe investigated the longitudinal association between Serum Urate (SU) level and Acute Myocardial Infarction (AMI), Stroke, End Stage Renal Failure (ESRF) and all-cause mortality.DesignWe conducted a retrospective hospital-based cohort study of individuals with gout managed in specialist outpatient clinics. Cox proportional hazards regression was used to estimate HR and 95% CI, with adjustments for potential confounders. Where the proportional hazard assumption was violated, stratified Cox regression was applied instead.SettingAn acute care tertiary hospital in Singapore.ParticipantsIndividuals with a first gout diagnosis between 2007–2017, identified through (i) primary discharge diagnosis, (ii) diagnosis from the Rheumatology SOC (iii) patient history of a clinical encounter at the Rheumatology SOC plus use of urate-lowering therapy/colchicine.Main outcome measuresAll-cause mortality, AMI, Stroke and ESRF ascertained through data linkage with the National Registry of Diseases Office.ResultsThe final cohort comprised 2,866 individuals. Post follow-up, there were 800 deaths and 362, 218 and 191 occurrences of AMI, ESRF and stroke respectively. Compared to the reference (second-lowest) SU quartile, being in the highest SU quartile was associated with a significantly increased hazard for mortality (HR:1.66, 95% CI:1.36–2.03), incident ESRF (HR:3.02, 95% CI:2.00-4.56), and increased hazard for incident AMI (HR:1.42, 95% CI:1.06–1.91). The p-trend for all 3 outcomes was significant. No significant association was found between SU quartile and hazard for incident stroke.ConclusionsThis study found that individuals with gout managed at SOC who had higher baseline SU levels had an increased hazard for all-cause mortality, ESRF, and AMI.Clinical trial numberNot applicable.

Metabolomic age (MileAge) predicts health and life span: A comparison of multiple machine learning algorithms.

Biological aging clocks produce age estimates that can track with age-related health outcomes. This study aimed to benchmark machine learning algorithms, including regularized regression, kernel-based methods, and ensembles, for developing metabolomic aging clocks from nuclear magnetic resonance spectroscopy data. The UK Biobank data, including 168 plasma metabolites from up to N = 225,212 middle-aged and older adults (mean age, 56.97 years), were used to train and internally validate 17 algorithms. Metabolomic age (MileAge) delta, the difference between metabolite-predicted and chronological age, from a Cubist rule-based regression model showed the strongest associations with health and aging markers. Individuals with an older MileAge were frailer, had shorter telomeres, were more likely to suffer from chronic illness, rated their health worse, and had a higher all-cause mortality hazard (HR = 1.51; 95% CI, 1.43 to 1.59; P < 0.001). This metabolomic aging clock (MileAge) can be applied in research and may find use in health assessments, risk stratification, and proactive health tracking.

Presentation and Outcomes of Histoplasmosis in Transplant Recipients: A Retrospective Single-Centre Cohort Study.

Histoplasmosis is an important infection among transplant recipients. Few studies have described its epidemiology and outcomes in the modern era. We conducted a retrospective analysis using medical records from a single center in the United States. We included patients 18 years or older with histoplasmosis. We divided the cohort into transplant recipients and immunocompetent groups to assess the outcomes in both groups. We utilized Cox hazard models to assess 90-day all-cause mortality. The study included 137 patients; with 28 (20%) transplant recipients. After the first year post-transplant, patients with lung transplant (30%) had a diagnosis of histoplasmosis. Transplant recipients exhibited a significantly higher incidence of disseminated histoplasmosis than immunocompetent patients (64%vs. 34%, p = 0.001), higher admission to ICU (39%vs. 16%; p = 0.01) and higher but not significant 90-day crude all-cause mortality (14%vs. 11%, p = 0.71). Patients with transplants had a higher, but not significant hazard of all-cause mortality at 90 days (hazard ratio: 1.5; 95% confidence interval: 0.4-3.9) when compared to immunocompetent patients. Transplant recipients were more commonly diagnosed with histoplasmosis after the first year post-transplantation, and although they exhibited a higher hazard for death at 90 days, this increase was not statistically significant.

All-Cause and Cause-Specific Mortality in Tourette Syndrome and Chronic Tic Disorder.

Tourette syndrome (TS) and chronic tic disorder (CTD) may be associated with an increased risk of mortality, but specific causes of death are poorly understood. In this matched cohort and sibling cohort study, we estimated the risk of all-cause and cause-specific mortality in individuals with TS/CTD, compared with unaffected matched individuals and unaffected full siblings. We identified all individuals diagnosed with TS/CTD in the Swedish National Patient Register who were living in the country between 1973 and 2020 and matched them (1:10) to individuals without TS/CTD from the general population. We also identified their siblings without TS/CTD. All-cause and cause-specific mortality outcomes, based on the International Classification of Diseases codes, were extracted from the Cause of Death Register. Covariates included sociodemographic variables and psychiatric disorders. Risks of mortality were estimated using Cox proportional hazards regression models. We included 10,280 individuals with TS/CTD and 102,800 matched individuals without TS/CTD. In adjusted models, individuals with TS/CTD had an 86% increased hazard of all-cause mortality (hazard ratio: 1.86, 95% confidence interval: 1.65-2.11). The increased risk was observed for both natural (particularly nervous, digestive, and respiratory system diseases) and unnatural causes of death (including suicides and accidents). The sibling comparison showed similar results, indicating that the associations were unlikely to be explained by familial confounding. Individuals with TS/CTD are at increased risk of death due to both natural and unnatural causes. As some of these deaths are potentially preventable, greater focus on the somatic health of individuals with TS/CTD is warranted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Roxadustat Efficacy and Safety in Patients Receiving Peritoneal Dialysis: Pooled Analysis of Four Phase 3 Studies.

Background/Objectives: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia of chronic kidney disease (CKD). The efficacy and safety of roxadustat compared with parenteral erythropoiesis-stimulating agents (ESAs) were evaluated in patients with anemia of CKD receiving peritoneal dialysis (PD). Methods: This analysis pooled data from four phase 3, multicenter, randomized, open-label, active-comparator studies (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES). The primary endpoints evaluated were hemoglobin change from baseline (CFB) to Weeks 28-36 without rescue therapy and hemoglobin CFB to Weeks 28-52 regardless of rescue therapy use. Safety data were reported. Results: This analysis included 422 patients (215 roxadustat, 207 ESA). Hemoglobin CFB to Weeks 28-36 without rescue therapy and hemoglobin CFB to Weeks 28-52 regardless of rescue therapy achieved non-inferiority for roxadustat vs. ESAs. The mean weekly dose of roxadustat was maintained over time (Weeks 1-4, 3.86 mg/kg/week; Weeks 101-104, 3.27 mg/kg/week), whereas the mean weekly ESA dose increased by 24% (Weeks 1-4, 115.70 IU/kg/week; Weeks 101-104, 143.40 IU/kg/week). Fewer patients treated with roxadustat received intravenous iron supplementation and rescue therapy, and patients treated with an ESA required blood transfusions sooner. Roxadustat-treated patients experienced a greater decrease in low-density lipoprotein cholesterol levels relative to baseline vs. ESA-treated patients. Treatment-emergent adverse events were similar in both treatment groups. Major adverse cardiovascular event (MACE), MACE plus unstable angina or congestive heart failure, and all-cause mortality hazard ratios were <1; the lower limit of the 95% CIs was <0.6, and the upper limit was >1.3. Conclusions: Roxadustat was non-inferior to ESAs in correcting and maintaining hemoglobin levels, with stable dosing and a comparable safety profile, in anemic patients receiving PD.

Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Liver Cirrhosis.

Comparing direct oral anticoagulants (DOACs) and warfarin's efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC). Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC. A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups. In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70). DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.

Mortality, Criminal Sanctions, and Court Diversion in People With Psychosis

People living with psychosis experience excess premature mortality and are overrepresented in criminal legal systems, but little is known about mortality associated with criminal sanctions or diversion in this population. To examine associations of different types of recent (past 2 years) criminal sanction, including court diversion, with mortality among people with psychosis. This population-based, retrospective, data-linkage cohort study was conducted using 6 routinely collected administrative data collections from New South Wales, Australia, relating to health, court proceedings, imprisonment, and mortality. Participants (adults aged ≥18 years hospitalized for psychotic disorders) entered observation at the time of discharge from their first psychosis-related hospital admission (or their 18th birthday if aged <18 years) between July 2001 and November 2017 and were followed-up until May 2019. Data were analyzed between February 2023 and April 2024. Recent (past 2 years) criminal sanction type, a time-varying variable with 5 categories: no recent criminal sanction, recent mental health court diversion, recent community sanction, current imprisonment, and recent prior imprisonment (ie, recent prison release). Causes of death were described, and age- and sex-specific mortality rates by recent criminal sanction type were calculated. In those younger than 65 years, Cox regression was used to examine associations of all-cause and external-cause mortality with recent criminal sanction type, adjusting for sociodemographic, health-related, and offense-related confounders. The cohort included 83 071 persons (35 791 female [43.1%]; 21 208 aged 25-34 years [25.5%]; median [IQR] follow-up, 9.5 [4.8-14.2] years), of whom 25 824 (31.1%) received a criminal sanction. There were 11 355 deaths. In those aged younger than 65 years, recent mental health court diversion, community sanctions, and prior imprisonment were associated with increased hazards of all-cause and external-cause mortality compared with no recent sanction, with the largest adjusted hazard ratios (aHRs) observed for recent prior imprisonment (all-cause mortality: aHR, 1.69; 95% CI, 1.50-1.91; external-cause mortality: aHR, 2.64; 95% CI, 2.27-3.06). In this cohort study of people with psychosis, recent criminal sanctions were associated with increased mortality irrespective of sanction type. These findings suggest that future research should develop strategies to improve health and safety in people with psychosis who have criminal legal system contact.

Association between warfarin and direct oral anticoagulants users and risk of mortality: cohort studies in England and Hong Kong

Abstract Background The evidence of the association between warfarin and risk of mortality compared with direct oral anticoagulants (DOACs) has been mixed in current literature. Purpose To investigate the association between all-cause mortality and warfarin, compared with DOACs. Methods Population-based cohort studies were conducted using the data from the Hong Kong Clinical Data Analysis and Reporting System (CDARS) and United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. People with atrial fibrillation aged ≥18 years who initiated warfarin or a DOAC during the study period (1st Jan 2014 - 31st Dec 2019) were identified. Follow-up started from the first date of oral anticoagulant prescription and ended at earliest of the date of death, the day before drug switching (between warfarin and DOACs), transferring out of the practice (CPRD Aurum only), last data collection date for the practice (CPRD Aurum only) or the end of study period. We estimated propensity score (PS) based on the list of potential confounders including demographics, co-morbidities, co-medications and polypharmacy. Cox proportional hazards regression model with PS-weighting was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among 227,190 new oral anticoagulant users, 54,367 (23.93%) died. The median follow-up was 2.96 and 2.45 years in CPRD and CDARS, respectively. Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin use (PS-weighted hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.89-0.99) in CPRD; while a higher hazard was observed in warfarin users (PS-weighted HR=1.31, 95% CI=1.24-1.39) in CDARS, versus DOAC users. Consistent results were seen in both databases when stratified warfarin users by Time in Therapeutic Range (TTR). We observed a lower hazard of all-cause mortality in warfarin users with TTR≥65% (PS-weighted HR=0.90, 95% CI=0.85-0.94 in CPRD; 0.87, 0.79-0.96 in CDARS) and increased hazard in warfarin users with TTR&amp;lt;65% (PS-weighted HR=1.37, 95% CI=1.25-1.49 in CPRD; 1.57, 1.48-1.66 in CDARS), versus DOAC users. Conclusions The hazard of all-cause mortality associated with warfarin compared with DOACs were found to be conflicting across databases. However, both databases consistently showed that an increased hazard of all-cause mortality was only found in warfarin users with TTR&amp;lt;65% but not in those with TTR≥65%, suggesting that the differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. We recommend that warfarin users with poor INR control warrant closer clinical attention and could be considered for a switch to DOACs.

Systemic inflammation and risk of death in patients with atherosclerotic cardiovascular disease and chronic kidney disease

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease stage 3 - 4 (CKD) affects 7% and 10% of the Danish population, respectively. Systemic inflammation (SI) contributes to destabilisation of atherosclerotic plaques and is characterized by elevated levels of C-reactive protein (CRP) in the blood. CKD is associated with SI and is independently associated with an increased risk of ASCVD. CRP levels ≥2 mg/L have been identified as a risk factor for mortality and major adverse cardiovascular events (MACE). Purpose To provide real-world evidence on the clinical burden of SI in patients diagnosed with ASCVD and CKD, using national health registers. Method Data from the Danish National Patient Registry from 1994-2022 was used to identify ASCVD patients by ICD-10 codes. CKD was identified by eGFR test results in the range [15 -59mL/min/1.73m2], in the Register of Laboratory Results for Research (RLRR). The latter diagnosis of ASCVD and CKD was set as index date. CRP-test results were extracted from RLRR and only individuals with at least two CRP tests were included. If two CRP-test results ≥2mg/L to &amp;lt; 20mg/L were observed less than six month apart, and within two years of index date, the individual was classified to have SI. The eGFR data from RLRR was available from 2011 onwards, with some regional differences in reporting. Individuals observed with CKD or ASCVD in the first year of eGFR availability were excluded to ensure a study of incident individuals. Individuals using select medications or diagnosed with selected chronic conditions thought to influence CRP levels were excluded. Additional population characteristics were extracted from corresponding national health and administrative registers. Hazard of all-cause mortality and MACE was analysed in a Cox proportional risk regression. Results From 2012 to 2022, a total of 19,162 individuals were eligible for the study population (SI: 13,039, No SI: 6,123). Median follow-up time was 4.1 and 8.2 years for individuals with or without SI, respectively. Median CRP two years before and after index date in the two groups was 7mg/L and 1mg/L. No clinically significant differences were found for demographic or socioeconomic characteristics. Patients with SI had more frequent history of hypertension, atrial fibrillation, COPD, heart failure and Type 2 diabetes before index, and higher risk of hypertension, atrial fibrillation, stroke, heart failure and type 2 diabetes after index. SI population had significantly increased hazard of mortality in a crude model (HR: 2.35, 95% CI: [2.22 – 2.50]), and in adjusted analysis HR: 2.06 ([1.92 - 2.21]). The corresponding hazard ratios for MACE were 1.9 ([1.81 – 2.01]) and 1.66 ([1.57 – 1.77]). The results were consistent across different model specifications and subgroups. Conclusion SI is associated with a significantly higher clinical burden of disease and a higher risk of all-cause mortality.Flowchart of inclusion/exclusionHazard ratio, overall and by subgroup

Cardiac rehabilitation attendance and outcomes 3 years after acute coronary syndrome (ACS): Linked national data of the SNAPSHOT ACS audit

Abstract Background In international guidelines, cardiac rehabilitation is recommended to reduce readmissions, mortality and improve disease management. However, evidence from a long-term follow-up in a representative cohort is scarce. Purpose To compare 3-year outcomes among acute coronary syndrome (ACS) survivors who attended cardiac rehabilitation programs and those who did not. Methods This was a follow-up of the SNAPSHOT ACS cohort in 1,920 Australians. Clinical data of those presenting with suspected ACS, hospitalised, discharged alive and followed for 18 months were linked to jurisdictional/national regulatory hospitalisation, mortality and pharmacotherapy records. Outcomes were all-cause and cardiovascular mortality, myocardial infarction (MI) and cardiovascular readmissions. Cox regression was used to analyse all-cause mortality, and Fine and Gray competing risk model for cardiovascular mortality, MI and cardiovascular readmissions, where non-cardiovascular mortality or all-cause mortality were competing events. The models were adjusted for age, sex, discharge diagnosis and coronary revascularisation. Results The cohort was aged 66±13.5 years; 60% were male, 31% had a discharge diagnosis of MI, and 490 (26%) attended cardiac rehabilitation. Cardiac rehabilitation attendees more frequently received coronary revascularisation and had a discharge diagnosis of MI during index admission. Attendees were more likely to be men (70% vs 57%, p&amp;lt;0.001) with a family history of coronary disease (43% vs 36%, p=0.008). The prescription of ≥3 guideline-indicated medications was higher in cardiac rehabilitation attendees. Compared to those who did not attend cardiac rehabilitation, the hazard of all-cause mortality was lower for the attendees (4.3% vs 8.6%, HR: 0.55, 95% CI: 0.34-0.91), but the hazard of MI and cardiovascular readmissions significantly greater in the attendees (17% vs 8.5%, HR: 1.99, 95% CI: 1.41-2.82; 42% vs 33%, HR: 1.34, 95% CI: 1.10-1.63; respectively) (Figure). There was insufficient cardiovascular mortality between groups to fit a statistical model (n=7 (1.4%) vs n=24 (1.7%), p=0.705). Conclusions Survivors of ACS attending cardiac rehabilitation were associated with reduced all-cause mortality and increased readmissions related to MI and cardiovascular disease at 3 years follow-up. These findings support secondary prevention strategies to mitigate mortality risk after ACS.

Siamese neural networks can identify subjects from anonymised ECGs

Abstract Background/Introduction Many research databases contain anonymised electrocardiograms (ECGs) linked to other sensitive information. ECGs hold features unique to individuals, potentially enabling subject identification from anonymised ECGs. Purpose We assessed if artificial intelligence approaches to output ECG pair similarity can re-identify individuals from anonymised ECGs. Additionally, we aimed to explore clinical risk prediction using ECG similarity over time. Methods We used a convolutional Siamese neural network (SNN), with a triplet loss function, to train a deep learning model determining if two ECGs belong to the same individual (Figure 1). The model aims to encode ECG inputs from same subjects closer than ECG inputs from different subjects. An ECG similarity score is output, corresponding to the probability two ECGs belong to the same subject. This continuous metric can be used in a binary manner. Below a threshold, two ECGs are classed as from the same individual. Our dataset comprised 72,455 secondary care subjects from a USA cohort with 4 to 75 ECGs each, totalling 864,283 ECGs. These were split 50:10:40% at the subject level for training, validation and testing. Results In 2,689,124 same-subject pairs and 2,689,124 different-subject pairs from the test set, the model achieves an accuracy of 91.68% against the binary threshold. This improves to 93.61% and 95.97% in outpatient and normal ECG subsets, respectively. We tested the model using a subject’s ECG to identify them from a group where only one ECG also belongs to that subject. 89.4% success rates occur in groups of 100 normal ECGs (if random, success would be 1%). 91.4%, 95.1%, and 96.3% success occurs when supplemented with subject gender, age (decade-bracket), and both, respectively. We calculated a model certainty score for this task. 99% success occurs when &amp;gt;95% certain. This is in 65% of group size 100 trials. In groups of 1000 normal ECGs, the success rate is 72.5% with no additional information, and 75.9%, 84.2% and 87.5% when supplemented as before (if random, success would be 0.1%). &amp;gt;95% certainty occurs in 33% of group size 1000 trials. For a given subject, ECG pair similarity proved clinically informative. The model accounts for slight variations within a subject’s ECGs, even when far apart in time (Figure 2A). However, it incorrectly predicts two ECGs as being from different individuals for substantial ECG morphology changes (Figure 2B), which could be used to identify clinical deterioration. The temporal evolution of ECG pair similarity reflects clinical trajectory, with greater dissimilarity associating with all-cause mortality (Hazard ratio, 1.22 per 1 standard deviation change, p &amp;lt; 0.0001). Conclusion(s) Anonymised ECGs retain information useful for subject re-identification. Whilst this implies possible ethical and data protection issues with large datasets, such approaches offer potential for continuous monitoring and identifying clinical deterioration.Figure 1Figure 2

Self-rated health in late adolescence as a predictor for mortality between 46 and 70 years of age

Self-rated health is a common assessment used in epidemiological research and an independent predictor of morbidity and mortality. We investigate if a single measure of self-rated health in late adolescence predict mortality between 46 and 70 years of age. This study was based on 47 286 Swedish men that conscribed 1969–1970 at age 18–20 and that were still alive in 1997. Self-rated health and data on potential explanatory factors (psychological factors, health status markers and health behaviors) were collected at conscription. Adult socioeconomic position in 1990 was derived from registries. Death and cause of death (cancer, cardiovascular disease, violent and alcohol abuse related disorders) were derived from the Causes of Death Register between 1997 and 2019. Conscripts that rated their health as fair or poor/very poor had significantly higher hazard of all-cause mortality than conscript that rated their health as very good (HRfair = 1.27, 95%CI:1.18–1.37 and HRpoor = 1.25, 95%CI:1.11–1.41) and disease-specific mortality. Adjusting for all explanatory factors attenuated the risk estimates by 9–100%. In conclusion, poor self-rated health reported in late adolescence predicts all-cause and disease-specific mortality between the ages of 46 and 70 years. Psychological factors and health behaviors measured at conscription may serve as potential explanatory factors underlying the predictive ability of self-rated health in late adolescence.

Kaposi's sarcoma-associated herpesvirus infection and its association with all-cause and cardiovascular mortality in the general adults: A prospective cohort study.

To investigate the association between Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) infection and both all-cause and cardiovascular mortality in a representative cohort of US adults, data from the National Health and Nutrition Examination Survey III (NHANES III; 1988‒1994) were analyzed, including 13,993 participants aged 18‒90 years who underwent KSHV serology evaluations. Mortality outcomes were ascertained through December 2019 using the National Death Index. Cox proportional hazards models were employed to examine the association between KSHV seropositivity and mortality, adjusting for potential confounders such as age, sex, ethnicity, body mass index, and serum TG. Over a median follow-up period of 26.5 years, 5503 deaths were recorded. KSHV seropositivity was associated with an increased hazard of all-cause mortality (Hazard Ratio [HR]: 1.32, 95% Confidence Interval [CI]: 1.03‒1.69) and cardiovascular mortality (HR: 1.58, 95% CI: 1.00‒2.50) after adjusting for age, sex, ethnicity, and body mass index. Notably, the association between KSHV infection and all-cause mortality persisted among women (HR: 1.32, 95% CI: 1.02‒1.72) after adjusting for all confounders, whereas the association with cardiovascular mortality was only statistically significant for men (HR: 1.90, 95% CI: 1.02, 3.53).KSHV infection may represent an independent risk factor for all-cause and cardiovascular mortality among US adults. These findings highlight the need for further research to validate these associations in independent populations and to elucidate the biological mechanisms underlying the observed increased mortality associated with KSHV infection.