Time-dependent Cox Regression Models Research Articles

Chronic kidney disease in patients with psoriatic arthritis: a cohort study

ObjectivesChronic kidney disease (CKD) is a comorbidity in psoriatic arthritis (PsA). We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes and identify...

Association of serum testosterone levels with left atrial size, function, and risk of atrial fibrillation in adult men: observational and mendelian randomization analyses

Abstract Background Numerous studies have investigated the association between serum testosterone levels, testosterone replacement therapy (TRT), and cardiovascular risk. However, research examining the relationship between testosterone levels and atrial fibrillation (AF) risk remains limited. We comprehensively analyzed the association between total testosterone (TT) levels, intermediary phenotypes such as left atrium (LA) size and function, and the risk of AF in middle-aged and older men. Methods We utilized data from the UK Biobank, a population-based prospective cohort, focusing on 179,988 White men who had complete serum TT level data and no AF history. Observational associations between TT levels and LA imaging traits, as well as AF risk, were estimated using multivariable regression and time-dependent Cox regression models, treating TT levels as a time-varying variable. Genetic associations were examined by Mendelian randomization (MR), using both UK Biobank and external large consortia genome-wide association study data. Results During the median follow-up of 11.8 years (IQR 10.9–12.5), we observed 13,847 incident AF cases (7.7%). Participants with normal TT levels (≥ 300 ng/dL) showed a 15% reduced risk of AF (HR of 0.85 [95% CI, 0.82–0.89]) compared to those with low TT (< 300 ng/dL). Interestingly, participants undergoing TRT experienced a 51% higher risk of AF (1.51 [1.09–2.07]). Furthermore, each 1-standard deviation increase in TT levels was associated with a reduced AF risk (OR of 0.91 [0.89–0.93]) and an improved LA emptying fraction (1.29 [1.06–1.58]). Applying age-specific cutoff values for low TT levels highlighted a more pronounced AF risk reduction in participants with normal TT. MR analyses supported these observations, suggesting potential causal relationships between TT levels and both LA function and AF risk. Conclusions Our findings suggest that low TT levels are associated with reduced LA function and increased risk of AF, both observationally and genetically, indicating that serum TT could serve as a surrogate marker or even a potential causal mediator in the development of AF.Abstract tableAbstract figure

Cardiovascular disease in pregnancy: Prevalence and obstetric outcomes in a Swedish population-based cohort study between 2000 and 2019.

The prevalence of cardiovascular disease during pregnancy (cardiovascular disease diagnosed before, during or up to 6 months after childbirth) and the risk of adverse outcomes associated with it have not been previously described in Sweden. This study examined trends in prevalence of cardiovascular disease and its association with maternal and perinatal outcomes, overall and by timing of diagnosis in relation to pregnancy. This population-based observational retrospective cohort study consisted of women aged 15-49 years who were registered in the Swedish Medical Birth Register 2000-2019. Prevalence was defined as annual diagnosis of cardiovascular disease per pregnant woman as numerator and all pregnant women per year as denominator. Adverse maternal and perinatal outcomes were analyzed using time-dependent Cox regression and Poisson regression models. Outcomes were obtained during and after childbirth up to 1 year postpartum, depending on the outcome. There were 2 069 107 births to 1 186 137 women (911 101 primiparous). The prevalence of cardiovascular disease among pregnant women in Sweden during 2000-2019 increased from 0.31% to 1.34%, for non-congenital cardiovascular disease, this was primarily driven by arrythmia (0.11%-0.58%). Primiparous women with cardiovascular disease had a higher risk of eclampsia over-all (aHR 4.50, 95% CI 2.01-10.05) and when diagnosed during pregnancy (aHR 3.22, 95% CI 1.21-8.61); admission to psychiatric ward overall (aHR 2.51, 95% CI 1.30-4.83), and when diagnosed during pregnancy (aHR 2.54, 95% CI 1.21-5.34); and one-year mortality when diagnosed before pregnancy (aHR 1.67, 95% CI 1.16-2.42) and when diagnosed postpartum (aHR 6.59, 95% CI 3.38-12.84), compared to those without cardiovascular disease. Children born to women with cardiovascular disease diagnosed both overall and in relation to timing of diagnosis had an increased risk of being born preterm and small for gestational age. Cardiovascular disease prevalence among pregnant women in Sweden increased during 2000-2019, primarily driven by arrhythmias. In primiparous women, the timing of diagnosis of cardiovascular disease is important for maternal and perinatal outcomes, including when diagnosed postpartum. This calls for awareness among all staff when planning pregnancy and monitoring women with cardiovascular disease throughout pregnancy and in the postpartum period.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways “BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation” and “AMAN pathway”. In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Anti-diabetic drug use and reduced risk of Parkinson's disease: A community-based cohort study

BackgroundEmerging evidence suggests a potential association between certain anti-diabetic drugs and a reduced risk of Parkinson's disease (PD). Limited population-based studies have investigated users of newer anti-diabetic drugs such as GLP-1 agonists or SGLT2 inhibitors. ObjectiveThe aim of this study was to assess the risk of PD among individuals with type 2 diabetes mellitus (T2DM) who were treated with various types of anti-diabetic drugs over time. MethodsA population-based cohort comprising T2DM patients aged over 30 who used metformin, GLP-1 agonists, thiazolidinediones, sulfonylureas, DPP4 inhibitors, SGLT2 inhibitors, or meglitinides between January 1, 1999 and December 31, 2018. Data were obtained between the diabetes registration and drug purchase databases of Maccabi Healthcare Services. Time-dependent Cox regression models, adjusted for sex, age, and comorbidities were employed to calculate the adjusted hazard ratios (HRs) for the PD risk associated with different anti-diabetic drugs over time. ResultsThe study population comprised 86,229 T2DM patients, with 53.9 % males. The mean age at the first anti-diabetic drug purchase was 59.0 ± 11.0 and 62.0 ± 11.0 years for men and women respectively. Compared to metformin, several drug types were associated with a significantly lower PD risk: thiazolidinediones (HR = 0.91, 95 % CI:0.074–1.14); DPP4 inhibitors (HR = 0.60, 95 % CI:0.53–0.67); meglitinides (HR = 0.63, 95 % CI:0.53–0.74); GLP-1 agonists (HR = 0.54, 95 % CI:0.39–0.73); and SGLT2 inhibitors (HR = 0.15, 95 % CI:0.10–0.21). ConclusionsOur results suggest a reduced risk of PD with certain anti-diabetic drugs, particularly SGLT2 inhibitors and GLP-1 agonists. Validation through extensive big-data studies is essential to confirm these results and to optimize PD prevention and management.

Association of the intergenerational structure with the onset of depressive symptoms among middle-aged and older adults in China.

Chinese family structure has undergone tremendous changes over the past few decades. Moreover, the association of the intergenerational structure with depression remains controversial. This study aimed to find out the association of the intergenerational structure and the onset of depressive symptoms among Chinese middle-aged and older adults. This study included 4,868 participants of the China Health and Retirement Longitudinal Study (CHARLS), who were enrolled in 2011 without depressive symptoms and followed up at least once later in 2013, 2015, 2018, and 2020. Taking the time-varying confounding effect into account, the time-dependent Cox regression models were used to estimate the association of the intergenerational structure and the onset of depressive symptoms. Among the studied middle-aged and older adults, compared to one-generation households, higher hazard ratios (HR) of developing depressive symptoms were found in three-generation households in the study population (HR = 1.21, 95% CI [1.08, 1.36]). Further, for female participants, skipping-generation households (HR = 1.38, 95% CI [1.05, 1.83]) and three-generation lineal households (HR = 1.21, 95% CI [1.02, 1.43]) were found to be significantly associated with new-onset depressive symptoms compared to empty-nest couples. For male participants, living alone (HR = 1.65, 95% CI [1.30, 2.11]), living in standardized nuclear households (HR = 1.27, 95% CI [1.06, 1.54]), impaired nuclear households (HR = 1.80, 95% CI [1.18, 2.76]), or three-generation lineal households (HR = 1.34, 95% CI [1.12, 1.60]) were found to have a significant association with the onset of depressive symptoms. This study found that males living alone, with unmarried children, or in three-generation lineal households, and females living with grandchildren were more likely to suffer from depressive symptoms. Therefore, special attention should be paid to people in these intergenerational structure subtypes.

Long-term exposure to low-level ozone and the risk of hypertension: A prospective cohort study conducted in a low-pollution region of southwestern China

BackgroundThe current evidence regarding the association between long-term exposure to ozone (O3) and hypertension incidence is limited and inconclusive, particularly at low O3 concentrations. Therefore, our research aims to investigate the potential link between long-term O3 exposure and hypertension in a region with low pollution levels. MethodsFrom 2010 to 2012, we conducted a cohort prospective study by recruiting nearly 10,000 attendees through multistage cluster random sampling in Guizhou Province, China. These individuals were followed up from 2016 to 2020, and 5563 cases were finally included in the analysis. We employed a high-resolution model with both temporal and spatial accuracy to estimate the maximum daily 8-h average O3 and utilized annual average O3 concentrations for three exposure periods (2009_10, 2007_10, 2005_10) as the exposure indicator. Time-dependent covariates Cox regression model was exerted to estimate the hazard ratios (HRs) of hypertension incidence. Generalized linear model was employed to assess the association between O3 and systolic, diastolic, pulse, and mean arterial pressure. The dose-response curve was explored using a restricted cubic spline function. Results1213 hypertension incidents occurred during 39,001.80 person-years, with an incidence density of 31.10/1000 Person Years (PYs). The average O3 concentrations during the three exposure periods were 66.76 μg/m3, 67.85 μg/m3, and 67.21 μg/m3, respectively. Per 1 μg/m3 increase in O3 exposure was associated with 11 % increase in the incidence of hypertension in the single-pollution model, and the association was more pronounced in Han, urban, and higher altitude areas. SBP, PP, and MAP were increased by 0.619 (95 % CI, 0.361–0.877) mm Hg, 0.477 (95 % CI, 0.275–0.679) mm Hg, 0.301 (95 % CI, 0.127–0.475) mm Hg, respectively. Furthermore, we observed a nonlinear exposure-response relationship between O3 and hypertension incidence. ConclusionsLong-term exposure to low-level O3 exposure is associated with an increased risk of hypertension.

The relationship between serum potassium levels and cardiac arrhythmias in left ventricular assist device (LVAD) recipients: a comprehensive analysis and prognostic evaluation.

This study aimed to comprehensively analyze the relationship between serum potassium (K+) levels and the risk of de novo cardiac arrhythmias in left ventricular assist device (LVAD) recipients. We performed a retrospective study using the INTERMACS registry. Data was collected on adult patients with available K+ measurements taken 1-month post-LVAD implantation. K+ levels were the main exposure of interest and were analyzed as a continuous and categorical variable (quartiles of baseline K+ distribution). The main outcome of interest was the occurrence of de novo arrhythmia events, either sustained (ventricular [VA] or supraventricular arrhythmia [SVA]) or not sustained (atrial fibrillation/flutter [AF]). All-cause mortality was evaluated as the secondary outcome. Multivariable adjusted time-dependent Cox regression models and natural splines were used to describe the relationship between the exposure and outcomes of interest. 10,570 patients met our inclusion criteria. A significant and consistent relationship was observed between the lowest quartile of longitudinal K+ and the risk of arrhythmic events (HR 1.28, 95% CI 1.08, 1.53, p = 0.005) as well as in the highest K+ quartile (HR 1.24, 95% CI 1.02, 1.49, p = 0.027). A similar relationship was confirmed in the stratified analysis of arrhythmia types for SVAs and AF. The data were reflected in a U shaped relationship. Similarly, the highest and lowest quartiles of longitudinal K+ were independently associated with a significant increase in the HR of death, which was reflected by a U shaped relationship. Our study reveals a significant U shaped relationship between low and high K + levels and cardiac arrhythmias in LVAD patients, particularly SVAs and AF. Both high and low K + levels negatively impacted patient survival.

Elevated Risk of Stroke in Young Adults After Traumatic Brain Injury: A Nationwide Study of 1 Million Individuals.

Although stroke is commonly perceived as occurring in older adults, traumatic brain injury, one of the risk factors for stroke, is a leading cause of death in the younger adults. This study evaluated stroke risk in young-to-middle-aged adults based on traumatic brain injury severity and stroke subtypes. For this retrospective, population-based, cohort study, data of adults aged 18 to 49 years who were diagnosed with traumatic brain injury were obtained from the Korean National Health Insurance Service between 2010 and 2017. Traumatic brain injury history was measured based on the International Classification of Diseases, Tenth Revision (ICD-10), codes. Posttraumatic brain injury stroke risk was analyzed using a time-dependent Cox regression model. At baseline, 518423 patients with traumatic brain injury and 518 423 age- and sex-matched controls were included. The stroke incidence rate per 1000 person-years was 3.82 in patients with traumatic brain injury and 1.61 in controls. Stroke risk was approximately 1.89 times as high in patients with traumatic brain injury (hazard ratio, 1.89 [95% CI, 1.84-1.95]). After excluding stroke cases that occurred within 12 months following traumatic brain injury, these significant associations remained. In the subgroup analysis, patients with brain injury other than concussion had an approximately 9.34-fold risk of intracerebral hemorrhage than did the controls. Stroke prevention should be a priority even in young-to-middle-aged adult patients with traumatic brain injury. Managing stroke risk factors through regular health checkups and modifying health-related behaviors is necessary to prevent stroke.

Risk and impact of cytomegalovirus infection in lymphoma patients treated with bendamustine.

Bendamustine is used to treat lymphoma with excellent efficacy but is known for its immunosuppressive effect. Cytomegalovirus (CMV) reactivation after bendamustine use has been reported. We aim to address the impact of CMV infection in lymphoma patients treated with bendamustine-containing regimens. We retrospectively analyzed lymphoma patients at Taipei Veterans General Hospital in Taiwan between September 1, 2010, and April 30, 2022. Clinically significant CMV infection (CS-CMVi) was defined as the first CMV reactivation after bendamustine use necessitating CMV therapy. Patients' baseline characteristics and laboratory data were recorded. The primary endpoint of the study was CS-CMVi. A time-dependent covariate Cox regression model was used to estimate the risk factors of CS-CMVi and mortality. A total of 211 lymphoma patients treated with bendamustine were enrolled. Twenty-seven (12.8%) had CS-CMVi. The cumulative incidence was 10.1 per 100 person-years during the three-year follow-up period. In the multivariate analysis, lines of therapy before bendamustine≥ 1 (95% CI 1.10-24.76), serum albumin < 3.5g/dL (95% CI 2.63-52.93), and liver disease (95% CI 1.51-28.61) were risk factors for CS-CMVi. In conclusion,CS-CMVi (95% confidence interval [CI] 1.23-10.73) was one of the major independent risk factors of mortality. Lines of therapy before bendamustine≥ 1, hypoalbuminemia, and liver disease were risk factors for CS-CMVi in lymphoma patients treated with bendamustine.

Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes

A nonadjuvanted bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF [Pfizer]) protein subunit vaccine was newly approved and recommended for pregnant individuals at 32 0/7 to 36 6/7 weeks' gestation during the 2023 to 2024 RSV season; however, clinical vaccine data are lacking. To evaluate the association between prenatal RSV vaccination status and perinatal outcomes among patients who delivered during the vaccination season. This retrospective observational cohort study was conducted at 2 New York City hospitals within 1 health care system among patients who gave birth to singleton gestations at 32 weeks' gestation or later from September 22, 2023, to January 31, 2024. Prenatal RSV vaccination with the RSVpreF vaccine captured from the health system's electronic health records. The primary outcome is preterm birth (PTB), defined as less than 37 weeks' gestation. Secondary outcomes included hypertensive disorders of pregnancy (HDP), stillbirth, small-for-gestational age birth weight, neonatal intensive care unit (NICU) admission, neonatal respiratory distress with NICU admission, neonatal jaundice or hyperbilirubinemia, neonatal hypoglycemia, and neonatal sepsis. Logistic regression models were used to estimate odds ratios (ORs), and multivariable logistic regression models and time-dependent covariate Cox regression models were performed. Of 2973 pregnant individuals (median [IQR] age, 34.9 [32.4-37.7] years), 1026 (34.5%) received prenatal RSVpreF vaccination. Fifteen patients inappropriately received the vaccine at 37 weeks' gestation or later and were included in the nonvaccinated group. During the study period, 60 patients who had evidence of prenatal vaccination (5.9%) experienced PTB vs 131 of those who did not (6.7%). Prenatal vaccination was not associated with an increased risk for PTB after adjusting for potential confounders (adjusted OR, 0.87; 95% CI, 0.62-1.20) and addressing immortal time bias (hazard ratio [HR], 0.93; 95% CI, 0.64-1.34). There were no significant differences in pregnancy and neonatal outcomes based on vaccination status in the logistic regression models, but an increased risk of HDP in the time-dependent model was seen (HR, 1.43; 95% CI, 1.16-1.77). In this cohort study of pregnant individuals who delivered at 32 weeks' gestation or later, the RSVpreF vaccine was not associated with an increased risk of PTB and perinatal outcomes. These data support the safety of prenatal RSVpreF vaccination, but further investigation into the risk of HDP is warranted.

Associations between long-term ambient PM2.5 exposure and the incidence of cardiopulmonary diseases and diabetes, attributable years lived with disability, and policy implication

Long-term exposure to ambient PM2.5 is known associated with cardiovascular and respiratory health effects. However, the heterogeneous concentrationresponse function (CRF) between PM2.5 exposure across different concentration range and cardiopulmonary disease and diabetes mellitus (DM) incidence, and their implications on attributable years lived with disability (YLD) and regulation policy has not been well-studied. In this retrospective longitudinal cohort study, disease-free participants (approximately 170,000 individuals, aged ≥ 30 years) from the MJ Health Database were followed up (2007–2017) regarding incidents of coronary heart disease (CHD), ischemic stroke, chronic obstructive pulmonary disease (COPD), lower respiratory tract infections (LRIs), and DM. We used a time-dependent nonlinear weight-transformation Cox regression model for the CRF with an address-matched 3-year mean PM2.5 exposure estimate. Town/district-specific PM2.5-attributable YLD were calculated by multiplying the disease incidence rate, population attributable fraction, disability weight, and sex-age group specific subpopulation for each disease separately. The estimated CRFs for cardiopulmonary diseases were heterogeneously with the hazard ratios (HRs) increased rapidly for CHD and ischemic stroke at PM2.5 concentration lower than 10 μg/m3, whereas the HRs for DM (LRIs) increased with PM2.5 higher than 15 (20) μg/m3. Women had higher HRs for ischemic stroke and DM but not CHD. Relative to the lowest observed PM2.5 concentration of 6 μg/m3 of the study population, the PM2.5 level with an extra risk of 0.1 % (comparable to the disease incidence) for CHD, ischemic stroke, DM, and LRIs were 8.59, 11.85, 22.09, and 24.23 μg/m3, respectively. The associated attributable YLD decreased by 51.4 % with LRIs reduced most (83.6 %), followed by DM (63.7 %) as a result of PM2.5 concentration reduction from 26.10 to 16.82 μg/m3 during 2011–2019 in Taiwan. The proportion of YLD due to CHD and ischemic stroke remained dominant (56.4 %-69.9 %). The cost-benefit analysis for the tradeoff between avoidable YLD and mitigation cost suggested an optimal PM2.5 exposure level at 12 μg/m3. CRFs for cardiopulmonary diseases, attributable YLD, and regulation level, may vary depending on the national/regional background and spatial distribution of PM2.5 concentrations, as well as demographic characteristics.

Duration of effectiveness of the COVID-19 vaccine in Japan: a retrospective cohort study using large-scale population-based registry data

BackgroundMost evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination.MethodsData obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates.ResultsAmong the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model with reference of non-vaccine group revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63–0.91]), two-dose (0.89 [0.85–0.93]), three-dose (0.80 [0.76–0.85]), four-dose (0.93 [0.88–1.00]), and five-dose (0.72 [0.62–0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21–0.81]), two-dose (0.44 [0.35–0.56]), three-dose (0.38 [0.30–0.47]), four-dose (0.20 [0.14–0.28]), and five-dose (0.11 [0.014–0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model with reference of non-vaccine group revealed significant preventive effects of the vaccine for 4 months for the incidence of COVID-19 and ≥ 6 months for hospitalization.ConclusionsVaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic.

Survival benefit of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a nationwide cohort study

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.

Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records

BackgroundThere is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers.MethodsWomen newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use.ResultsThe combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02).ConclusionsWe observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Associations of short-term changes in obesity indices with all-cause mortality and cardiovascular disease.

This study aimed to investigate how short-term changes (1-, 3-, and 5-year) in obesity measures affect mortality and cardiovascular disease (CVD) risk. We analyzed longitudinal data from the MJ Health Centre (n = 43,304 for the 1-year study; 24,295 for the 3-year study; 16,138 for the 5-year study) with median follow-up periods of 15.8, 13.9, and 12.3 years, respectively. Associations of short-term obesity indices changes with mortality and Framingham Risk Score changes were explored using time-dependent coefficient Cox regression models, restricted cubic splines, and multivariable linear regression models. All-cause mortality was negatively associated with short-term weight and BMI changes, with greater reductions causing poorer outcomes. Compared with stable groups, short-term reduced weight and BMI were associated with greater risks of all-cause mortality and CVD-specific mortality (5-year study only). Also, either 1- and 3-year reducedor 3-year increased waist circumference and waist to height ratio were related to higher all-cause and CVD deaths than stable groups, respectively. Nonlinear relationships indicated lower cutoff values for short-term changes in obesity indices in predicting all-cause mortality. Decreased obesity indices significantly improved CVD profiles. Short-term changes in obesity indices show complex mortality risks, urging personalized approaches beyond a simple weight loss focus.

Prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning: a retrospective study.

Diquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning. This was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC). Among the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p < 0.05). Plasma Diquat concentration at admission (HR = Exp (0.032-0.059 × ln (t))) and PSS within 24 h after admission (HR: 4.470, 95%CI: 1.604 ~ 12.452, p = 0.004) were independent prognostic factors in the time-dependent Cox regression model. Plasma DQ concentration at admission and PSS within 24 h after admission are independent prognostic factors for the in-hospital case fatality rate in patients with acute oral DQ poisoning. The prognostic value of plasma DQ concentration decreased with time.

Association of Residential Greenness Exposure with Depression Incidence in Adults 50 Years of Age and Older: Findings from the Cohort Study on Global AGEing and Adult Health (SAGE) in China.

Depression is a social and public health problem of great concern globally. Identifying and managing the factors influencing depression are crucial for preventing and decreasing the burden of depression. Our objectives are to explore the association between residential greenness and the incidence of depression in an older Chinese population and to calculate the disease burden of depression prevented by greenness exposure. This study was the Chinese part of the World Health Organization Study on Global AGEing and Adult Health (WHO SAGE). We collected the data of 8,481 residents years of age in China for the period 2007-2018. Average follow-up duration was 7.00 () years. Each participant was matched to the yearly maximum normalized difference vegetation index (NDVI) at their residential address. Incidence of depression was assessed using the Composite International Diagnostic Interview (CIDI), self-reports of depression, and/or taking depression medication. Association between greenness and depression was examined using the time-dependent Cox regression model with stratified analysis by sex, age, urbanicity, annual family income, region, smoking, drinking, and household cooking fuels. Furthermore, the prevented fraction (PF) and attributable number (AN) of depression prevented by exposure to greenness were estimated. Residential greenness was negatively associated with depression. Each interquartile range (IQR) increase in NDVI buffer was associated with a 40% decrease [; 95% confidence interval (CI): 0.37, 0.97] in the risk of depression incidence among the total participants. Subgroup analyses showed negative associations in urban residents (; 95% CI: 0.12, 0.86) vs. rural residents, in high-income residents (; 95% CI: 0.11, 0.71) vs. low-income residents, and in southern China (; 95% CI: 0.26, 0.95) vs. northern China. Over 8.0% (; 95% CI: 1.38%, 15.40%) and 1,955,199 (95% CI: 310,492; 3,464,909) new cases of depression may be avoided by increasing greenness exposures annually across China. The findings suggest protective effects of residential greenness exposure on depression incidence in the older population, particularly among urban residents, high-income residents, and participants living in southern China. The construction of residential greenness should be included in community planning. https://doi.org/10.1289/EHP13947.

Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database

ObjectivesTo compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients...

#3028 Predictive validity of the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS©) after renal transplantation

Abstract Background and Aims Adherence towards immunosuppressive medication is crucial for allograft survival after renal transplantation. However, its assessment in daily clinical practice remains challenging. The BAASIS© questionnaire, is a validated self-report instrument to detect non-adherence. However, its predictive validity for clinical relevant consequences of non-adherence needs to be established. Method The prospective AdTorque-trial (DRKS00026674) includes a consecutive cohort of 226 adult kidney graft recipients transplanted at the Medical University of Vienna between 01/2018 and 12/2019. Medication adherence was monitored up to two years by a multi-component assessment including the BAASIS©, electronic drug monitoring, pharmacy refill records, tacrolimus trough level, records by medical personal, individual evaluation by a transplant psychologist and concurrent immune monitoring by the quantification of Torque Teno virus load. The BAASIS© was applied at three-month intervals during the first year and at 24 months during routine follow-up visits. The adherence phases implementation and persistence were assessed by three items (i.e. taking, timing and dose-reduction) and one item of the BAASIS©. Non-adherence was defined by YES on any of these items. The primary clinical outcome was the occurrence of biopsy-proven allograft rejection during a maximum clinical follow-up of up to 4 years after transplantation. Herein we present the preliminary analysis of the multimodal monitoring focusing on the BAASIS© questionnaire. Results Of all 226 recipients (33% female, median age 57 years), 153 completed the adherence monitoring for 2 years, resulting in a total of 973 BAASIS© assessments. Non-adherence was reported at least once by 124 (55%) recipients and 67 recipients (30%) revealed non-adherence multiple times. The proportion of non-adherent recipients increased from 11% to 31% within the first three months and was between 27% to 32% at subsequent visits from month 6 to 24 post-transplant. Issues in the punctual timing of dose taking was the most frequent cause for non-adherence. During the clinical follow-up of 44 months (median, IQR 12-48), non-adherent recipients had a significantly higher rate of biopsy-proven rejection than adherent recipients (25%, n = 30 vs. 7%, n = 7; p &amp;lt; 0.001). A time-dependent cox regression model showed that non-adherence assessed by the BAASIS© predicted an increased risk for allograft rejection (HR 2.87, 95% CI 1.47-5.6). Conclusion Medication non-adherence was substantially reported already in early phases post-transplant and was associated with an increased risk for allograft rejection. Our analysis demonstrated the predictive validity of the BAASIS©, a self-report instrument which can easily be integrated in daily transplant practice. Regular adherence assessments might identify patients at risk for poor clinical outcome due to medication non-adherence and provide rationale for intervention.