Cause-specific Mortality Outcomes Research Articles

#2526 Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Abstract Background and Aims Chronic kidney disease (CKD) is a growing global health concern. In recent years, studies have increasingly focused on the differential risk profile of diseases between men and women. Current evidence suggests that sex-linked biological and behavioral differences may play a key role in influencing the incidence, prevalence, and outcomes of diseases. Similarly, previous studies have demonstrated a differential risk profile in the prevalence, progression, and outcomes of CKD between men and women. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. Method We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73 m². The outcomes were CKD-related complications (hypertension, anemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. Values of eGFR over which the log-odds (for CKD-related complications outcomes) or log-hazard (for all-cause and cause-specific mortality outcomes) was found to be significantly different from zero (i.e., 95% CI for the smooth term did not contain zero) were identified as thresholds of statistical significance. Results The study included 49, 562 participants (50.31% women, 49.68% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modeling eGFR as a natural spline revealed varied significance thresholds between sexes for anemia and hyperparathyroidism. We found a significantly (P < 0.05) higher proportion of women with anemia downstream an eGFR cut-off of 69 mL/min per 1.73 m2, which was lower than the cut-off in men; a significantly higher proportion of men with anemia was observed downstream an eGFR cut-off of 76 mL/min per 1.73 m2. However, the relationship was more pronounced in women than in men; thus, at an eGFR cut-off of 41 mL/min per 1.73 m2, the proportion of women with anemia was significantly higher (P < .05) (Figure). Similarly, a higher proportion of women with hyperparathyroidism were observed downstream an eGFR cut-off of 73 mL/min per 1.73 m2, which was lower than in men; a significantly higher proportion of men (P < .05) was observed downstream an eGFR cut-off of 89 mL/min per 1.73 m2 (Figure). Furthermore, although no sex differences were observed in terms of eGFR thresholds for hyperphosphatemia, a more pronounced relationship was observed in men. Thus, at an eGFR cut-off of 38 mL/min per 1.73 m2, the proportion of men with hyperphosphatemia was significantly higher (P < .05) than that of women (Figure). We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR Conclusion Research shows sex disparities in most CKD-related complications. Men develop anemia and hyperparathyroidism earlier, women show steeper anemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Association of secondhand smoke exposure with all-cause mortality and cardiovascular death in patients with hypertension: Insights from NHANES

Background and aimThe impact of environmental chemical exposure on blood pressure (BP) is well-established. However, the relationship between secondhand smoke exposure (SHSE) and mortality in hypertensive patients in the general population remains unclear. Methods and resultsThis cohort study included US adults in the National Health and Nutrition Examination Survey from 2007 to 2018. All-cause mortality and cause-specific mortality outcomes were determined by associating them with the National Death Index records. Cox proportional risk models were used to estimate hazard ratios (HRs) for all-cause mortality and cardiovascular disease (CVD) mortality, and 95% confidence intervals (CIs) for SHSE. The cohort included 10,760 adult participants. The mean serum cotinine level was 0.024 ng/mL. During a mean follow-up period of 76.9 months, there were 1729 deaths, including 469 cardiovascular disease deaths recorded. After adjusting for lifestyle factors, BMI, hypertension duration, medication use, and chronic disease presence, the highest SHSE was significantly associated with higher all-cause and CVD mortality. ConclusionsThis study demonstrates that higher SHSE is significantly associated with higher all-cause mortality and CVD mortality. Further research is necessary to elucidate the underlying mechanisms.

Association of serum 25-hydroxyvitamin D concentration with all-cause and cause-specific mortality in hypertensive patients

Background and aimsTo examine the association of serum 25-hydroxyvitamin D [25(OH)D] with all-cause mortality and disease-specific mortality in patients with hypertension. Methods and resultsThis cohort study included US adults in the National Health and Nutrition Examination Survey from 2007 to 2018. All-cause mortality and cause-specific mortality outcomes were determined by association with National Death Index records. Cox proportional risk models were used to estimate hazard ratios (HRs) for all-cause mortality and cause-specific mortality and 95% confidence intervals (CIs) for serum 25(OH)D concentrations. The cohort included 10,325 adult participants. The mean serum 25(OH)D level was 65.87 nmol/L, and 32.2% of patients were vitamin D deficient (<50 nmol/L). During a mean follow-up of 77 months, 1290 deaths were recorded, including 345 cardiovascular deaths and 237 cancer deaths. Patients with higher serum 25(OH)D were more likely to have lower all-cause mortality and cardiovascular mortality than those with serum 25(OH)D < 25.00 nmol/L. For cancer mortality in hypertensive patients, vitamin D may not have a predictive role in this. ConclusionsThis study shows that higher 25(OH)D levels are significantly associated with lower all-cause mortality and cardiovascular disease (CVD) mortality. These findings suggest that maintaining adequate vitamin D status may reduce the risk of death in patients with hypertension.

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks. Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality. Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically predicted 25(OH)D with coronary heart disease (odds ratio [OR] per 10 nmol/L higher genetically-predicted 25(OH)D concentration 0·98, 95% CI 0·95-1·01), stroke (1·01, [0·97-1·05]), or all-cause mortality (0·99, 0·95-1·02). Null findings were also observed in genetic analyses for cause-specific mortality outcomes, and in stratified genetic analyses for all outcomes at all observed levels of 25(OH)D concentrations. Stratified Mendelian randomisation analyses suggest a lack of causal relationship for 25(OH)D concentrations with both cardiovascular and mortality outcomes for individuals at all levels of 25(OH)D. Our findings suggest that substantial reductions in mortality and cardiovascular morbidity due to long-term low-dose vitamin D supplementation are unlikely even if targeted at individuals with low vitamin D status. British Heart Foundation, Medical Research Council, National Institute for Health Research, Health Data Research UK, Cancer Research UK, and International Agency for Research on Cancer.

Comparison of Vital Status, Cause of Death, and Follow-Up after Hematopoietic Cell Transplantation in Linked Center for International Blood and Marrow Transplant Research and California Cancer Registry Data, 1991 to 2018

Assessing outcomes following hematopoietic cell transplantation (HCT) poses challenges due to the necessity for systematic and often prolonged patient follow-up. Linking the HCT database of the Center for International Blood and Marrow Transplant Research (CIBMTR) with cancer registry data may improve long-term outcome ascertainment, but the reliability of mortality data in death certificates from cancer registries among HCT recipients remains unknown. We compared the classification of vital status and primary cause of death (COD), as well as the length of follow-up between the CIBMTR and California Cancer Registry (CCR) to assess the possibility of supplementing the CIBMTR with cancer registry data. This retrospective study leveraged a linked CIBMTR-CCR dataset. We included patients who were California residents at the time of HCT and received a first allogeneic (allo) or autologous (auto) HCT for a hematologic malignancy diagnosed during 1991-2016. Follow-up was through 2018. We analyzed 18,450 patients (alloHCT, n = 8232; autoHCT, n = 10,218). The Vital status agreement was 97.7% for alloHCT and 97.2% for autoHCT. Unknown COD was higher in CIBMTR (12.9%) than in CCR (1.6%). After excluding patients with unknown COD information, the overall agreement of primary COD (cancer versus noncancer) was 53.7% for alloHCT and 83.2% for autoHCT. This agreement was lower within the first 100 days post-HCT (alloHCT, 31.0%; autoHCT, 54.6%). Compared with CIBMTR, deaths due to cancer were higher in CCR (alloHCT, 90.0%; autoHCT, 90.1% versus alloHCT, 47.3%; autoHCT, 82.5% in CIBMTR). CIBMTR reports more frequently noncancer-related deaths, including graft-versus-host disease and infections. The cumulative incidence of cancer-specific mortality at 20 years differed, particularly for alloHCT (CCR, 53.7%; CIBMTR, 27.6%). The median follow-up among alive patients was longer in CCR (alloHCT, 6.0 years; autoHCT, 4.7 years) than in CIBMTR (alloHCT, 5.0 years; autoHCT, 3.8 years). Our findings highlight the completeness of vital status data in CIBMTR but reveal substantial disagreement in primary COD. Consequently, caution is required when interpreting HCT studies that use only death certificates to estimate cause-specific mortality outcomes. Improving the accuracy of COD registration and follow-up completeness by developing communication pathways between cancer registries and hospital-based cohorts may enhance our understanding of late effects and long-term outcomes among HCT survivors.

Circulating oxysterols and prognosis among women with a breast cancer diagnosis: results from the MARIE patient cohort

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide, and underlying mechanistic pathways associated with breast cancer-specific and non-breast cancer-related deaths are of importance. Emerging evidence suggests a role of oxysterols, derivates of cholesterol, in multiple chronic diseases including breast cancer and coronary artery diseases. However, associations between oxysterols and survival have been minimally studied in women diagnosed with breast cancer. In this large breast cancer patient cohort, we evaluated associations between a panel of circulating oxysterols and mortality and recurrence outcomes.MethodsConcentrations of 13 circulating oxysterols representing different pathways of cholesterol metabolism were quantified using liquid-chromatography mass-spectrometry. Associations between baseline levels of oxysterols and cause-specific mortality outcomes and recurrence following a breast cancer diagnosis were assessed in 2282 women from the MARIE study over a median follow-up time of 11 years. We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazard models and competing risks models.ResultsWe observed no associations for circulating oxysterols and breast cancer-specific outcomes. Higher levels of six oxysterols were associated with an increased risk of cardiovascular disease death, including 24S-hydroxycholesterol (alternative bile acid pathway, HRlog2 = 1.73 (1.02, 2.93)), lanosterol (cholesterol biosynthesis pathway, HRlog2 = 1.95 (1.34, 2.83)), 7-ketocholesterol (HRlog2 = 1.26 (1.03, 1.55)), 5α,6α-epoxycholesterol (HRlog2 = 1.34 (1.02–1.77)), and 5a,6β-dihydroxycholestanol (HRlog2 = 1.34 (1.03, 1.76)). After adjusting for multiple comparisons, none of the associations were statistically significant.ConclusionWe provide first evidence on a range of circulating oxysterols and mortality following a breast cancer diagnosis, contributing to a better understanding of associations between different pathways of cholesterol metabolism and prognosis in women with a breast cancer diagnosis. The findings of this study suggest circulating oxysterols may be associated with cardiovascular mortality among women diagnosed with breast cancer. Further studies are needed to evaluate these oxysterols as potential markers of risk for cardiovascular mortality among women with a breast cancer diagnosis as well as their clinical potential.

Short-term exposure to PM2.5 and 1.5 million deaths: a time-stratified case-crossover analysis in the Mexico City Metropolitan Area

BackgroundSatellite-based PM2.5 predictions are being used to advance exposure science and air-pollution epidemiology in developed countries; including emerging evidence about the impacts of PM2.5 on acute health outcomes beyond the cardiovascular and respiratory systems, and the potential modifying effects from individual-level factors in these associations. Research on these topics is lacking in low and middle income countries. We aimed to explore the association between short-term exposure to PM2.5 with broad-category and cause-specific mortality outcomes in the Mexico City Metropolitan Area (MCMA), and potential effect modification by age, sex, and SES characteristics in such associations.MethodsWe used a time-stratified case-crossover study design with 1,479,950 non-accidental deaths from the MCMA for the period of 2004–2019. Daily 1 × 1 km PM2.5 (median = 23.4 μg/m3; IQR = 13.6 μg/m3) estimates from our satellite-based regional model were employed for exposure assessment at the sub-municipality level. Associations between PM2.5 with broad-category (organ-system) and cause-specific mortality outcomes were estimated with distributed lag conditional logistic models. We also fit models stratifying by potential individual-level effect modifiers including; age, sex, and individual SES-related characteristics namely: education, health insurance coverage, and job categories. Odds ratios were converted into percent increase for ease of interpretation.ResultsPM2.5 exposure was associated with broad-category mortality outcomes, including all non-accidental, cardiovascular, cerebrovascular, respiratory, and digestive mortality. A 10-μg/m3 PM2.5 higher cumulative exposure over one week (lag06) was associated with higher cause-specific mortality outcomes including hypertensive disease [2.28% (95%CI: 0.26%–4.33%)], acute ischemic heart disease [1.61% (95%CI: 0.59%–2.64%)], other forms of heart disease [2.39% (95%CI: -0.35%–5.20%)], hemorrhagic stroke [3.63% (95%CI: 0.79%–6.55%)], influenza and pneumonia [4.91% (95%CI: 2.84%–7.02%)], chronic respiratory disease [2.49% (95%CI: 0.71%–4.31%)], diseases of the liver [1.85% (95%CI: 0.31%–3.41%)], and renal failure [3.48% (95%CI: 0.79%–6.24%)]. No differences in effect size of associations were observed between age, sex and SES strata.ConclusionsExposure to PM2.5 was associated with non-accidental, broad-category and cause-specific mortality outcomes beyond the cardiovascular and respiratory systems, including specific death-causes from the digestive and genitourinary systems, with no indication of effect modification by individual-level characteristics.

Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study

There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.

Evaluation of Health Economic Loss Due to Particulate Matter Pollution in the Seoul Subway, South Korea.

Evaluating an illness's economic impact is critical for developing and executing appropriate policies. South Korea has mandatory national health insurance in the form of NHIS that provides propitious conditions for assessing the national financial burden of illnesses. The purpose of our study is to provide a comprehensive assessment of the economic impact of PM2.5 exposure in the subway and a comparative analysis of cause-specific mortality outcomes based on the prevalent health-risk assessment of the health effect endpoints (chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD)). We used the National Health Insurance database to calculate the healthcare services provided to health-effect endpoints, with at least one primary diagnosis in 2019. Direct costs associated with health aid or medicine, treatment, and indirect costs (calculated based on the productivity loss in health effect endpoint patients, transportation, and caregivers, including morbidity and mortality costs) were both considered. The total cost for the exposed population for these endpoints was estimated to be USD 437 million per year. Medical costs were the largest component (22.08%), followed by loss of productivity and premature death (15.93%) and other costs such as transport and caregiver costs (11.46%). The total incurred costs (per 1000 persons) were accounted to be USD 0.1771 million, USD 0.42 million, and USD 0.8678 million for COPD, Asthma, and IHD, respectively. Given that the economic burden will rise as the prevalence of these diseases rises, it is vital to adopt effective preventative and management methods strategies aimed at the appropriate population.

Handgrip strength measurement protocols for all-cause and cause-specific mortality outcomes in more than 3 million participants: A systematic review and meta-regression analysis

Handgrip strength is a strong predictor of the risk of mortality. The objective of this systematic review was to analyse handgrip strength measurement protocols used in all-cause and cause-specific mortality studies. A systematic search of PubMed/MEDLINE, Web of Science and Scopus was conducted from inception to February 2022. Prospective cohort studies with objective measures of handgrip strength were included. Studies had to report at least one all-cause, cancer, or cardiovascular mortality outcome. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Meta-regression was used to quantify the bias associated with handgrip strength values in relation to the use of different measurement protocols. Forty-eight studies with a total of 3,135,473 participants (49.6% women) were included. Half of the studies controlled body position, 39.6% arm position, 33.3% elbow position, 12.5% wrist position, 13% handgrip duration, 23% hand-adjustment to dynamometer and 12.5% verbal encouragement. The number of measurements, the laterality of the hand tested, and the estimation method of the handgrip strength value varied considerably between the study protocols. The spline regression model showed a non-linear inverse association between the values of handgrip strength and the number of protocol items controlled. Handgrip strength was higher when the number of measurements per hand or arm position was not controlled. Conversely, handgrip strength was lower when elbow position was not controlled or verbal encouragement were not provided. In general, the protocols used to assess handgrip strength in mortality studies are incomplete and highly heterogeneous. Handgrip strength values were higher when studies controlled fewer handgrip strength measurement protocol variables. There is a need to improve the controlling of handgrip strength measurement protocols and to standardise the method to enhance the accuracy of mortality risk estimates associated with handgrip strength. CRD42022334929.

Associations of periodontal disease and tooth loss with all-cause and cause-specific mortality in the Sister Study.

Studies have found that periodontal disease and tooth loss are associated with increased mortality; however, associations with cause-specific mortality and all-cause mortality within specific subgroups have not been thoroughly investigated. We examined the association of self-reported periodontal disease and disease/decay-related tooth loss with subsequent all-cause and cause-specific mortality in the Sister Study, a prospective cohort study of 50,884 women aged 35-74 years at baseline, whose sister was diagnosed with breast cancer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations were calculated with adjustment for relevant confounders. With a mean follow-up of 10.9 years (range 0.1-14.3), 2058 women died. Participants with periodontal disease had a slightly higher rate of all-cause mortality (HR=1.08, 95% CI 0.98-1.19), while participants with tooth loss had an increased rate of all-cause mortality (HR=1.15, 95% CI 1.05-1.26). For cause-specific mortality, women with tooth loss had increased rates of death from circulatory system diseases, respiratory system diseases, and endocrine/metabolic diseases. Results varied in stratified models, but no heterogeneity across strata was found. In this large prospective study, periodontal disease and tooth loss were associated with all-cause and certain specific cause-specific mortality outcomes.

Long-term exposure to ambient particulate matter components and mortality: results from six European administrative cohorts within the ELAPSE project

BACKGROUND AND AIM: Evidence of the association between long-term exposure to ambient particulate matter components and mortality is inconsistent. We evaluated this association in six large administrative cohorts in the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) project. METHODS: We analysed data from country-wide administrative cohorts in Norway, Denmark, the Netherlands, Belgium, Switzerland and in Rome (Italy). Annual 2010 mean concentrations of copper (Cu), iron (Fe), sulfur (S) and zinc (Zn) in PM2.5 were estimated using 100x100m Europe-wide land use regression models assigned to the participants’ residential addresses. We applied cohort-specific Cox proportional hazard models controlling for area- and individual-level covariates to evaluate associations with natural, cardiovascular, non-malignant respiratory and lung cancer mortality. Two pollutant models adjusting for PM2.5 or NO2 were also applied. We pooled cohort specific estimates using a random effects meta-analysis. RESULTS:We included 27 million participants contributing more than 240 million person-years. Cu, Fe and S were associated with natural mortality [Hazard Ratios (HRs) (95% CI): 1.037 (1.014, 1.060) per 5 ng/m³ Cu; 1.069 (1.031, 1.108) per 100 ng/m³ Fe; 1.036 (1.016, 1.057) per 200 ng/m³ S] even after controlling for PM2.5 [e.g. 1.048 (1.022, 1.074) for Fe]. Adjustment for NO2 decreased HRs to unity [e.g. 0.994 (0.954, 1.036) for Fe]. Associations with cardiovascular mortality were weaker and non-significant. We found positive significant associations of Cu, Fe and S with non-malignant respiratory [HRs: 1.047, 1.099 and 1.043, respectively] and lung cancer mortality [HRs: 1.091, 1.160 and 1.102, respectively] in single pollutant models, though only the effect of Fe persisted after control for PM2.5. CONCLUSIONS:Our results indicate associations of long-term exposure to PM2.5 components with natural and cause-specific mortality outcomes related to non-tailpipe emissions (Cu and Fe) and long-range transport (S). However, associations did not persist after NO2 adjustment. KEYWORDS: Air pollution, Particle components, Long-term exposure, Environmental epidemiology, Survival, Mortality

Long-term exposure to low levels of air pollution and mortality adjusting for road traffic noise: A Danish Nurse Cohort study

BackgroundThe association between air pollution and mortality is well established, yet some uncertainties remain: there are few studies that account for road traffic noise exposure or that consider in detail the shape of the exposure–response function for cause-specific mortality outcomes, especially at low-levels of exposure. ObjectivesWe examined the association between long-term exposure to particulate matter [(PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10)], and nitrogen dioxide (NO2) and total and cause-specific mortality, accounting for road traffic noise. MethodsWe used data on 24,541 females (age > 44 years) from the Danish Nurse Cohort, who were recruited in 1993 or 1999, and linked to the Danish Causes of Death Register for follow-up on date of death and its cause, until the end of 2013. Annual mean concentrations of PM2.5, PM10, and NO2 at the participants’ residences since 1990 were estimated using the Danish DEHM/UBM/AirGIS dispersion model, and annual mean road traffic noise levels (Lden) were estimated using the Nord2000 model. We examined associations between the three-year running mean of PM2.5, PM10, and NO2 with total and cause-specific mortality by using time-varying Cox Regression models, adjusting for individual characteristics and residential road traffic noise. ResultsDuring the study period, 3,708 nurses died: 843 from cardiovascular disease (CVD), 310 from respiratory disease (RD), and 64 from diabetes. In the fully adjusted models, including road traffic noise, we detected associations of three-year running mean of PM2.5 with total (hazard ratio; 95% confidence interval: 1.06; 1.01–1.11), CVD (1.14; 1.03–1.26), and diabetes mortality (1.41; 1.05–1.90), per interquartile range of 4.39 μg/m3. In a subset of the cohort exposed to PM2.5 < 20 µg/m3, we found even stronger association with total (1.19; 1.11–1.27), CVD (1.27; 1.01–1.46), RD (1.27; 1.00–1.60), and diabetes mortality (1.44; 0.83–2.48). We found similar associations with PM10 and none with NO2. All associations were robust to adjustment for road traffic noise. DiscussionLong-term exposure to low-levels of PM2.5 and PM10 is associated with total mortality, and mortality from CVD, RD, and diabetes. Associations were even stronger at the PM2.5 levels below EU limit values and were independent of road traffic noise.

Ozone pollution in Chinese cities: Assessment of seasonal variation, health effects and economic burden

The ground-level ozone (O3) concentration in the urban regions of China has become an increasingly noticeable environmental problem in recent years. Many epidemiological studies have reported the association between O3 pollution and mortality, only a few studies have focused on the O3-related mortality and corresponding economic effects at the Chinese city and province level. This study reports the seasonal variation of ground-level O3 in 338 cities of China during the year 2016 and evaluates its effect on premature mortality and economic loss. It further illustrates the differences in cause-specific mortality outcomes of the log-linear and linear model, two of the prominently used methods for estimating health effects. In 2016, the annual average daily maximum 8-h O3 concentration in China ranged between 74 and 201 μg/m3 (138 ± 24.7 μg/m3). 30% of the total population was exposed to >160 μg/m3 O3 concentration (Chinese national ambient air quality standard) and about 67.2% urban population lived in exposure above the WHO recommended O3 concentrations (100 μg/m3). The estimated national O3-attributable mortality was 74.2 × 103 (95% CI: 16.7×103–127×103) in the log-linear model, whereas, the total O3-related mortality using the linear model was 69.6 × 103 (95% CI: 16.2 × 103–115 × 103). The exposure to O3 caused a nationwide economic loss of about 7.6 billion US$ (range: 1.7–12.9) in 2016. This study uniquely provides most comprehensive coverage of the Chinese cities for O3 associated mortality utilizing ground level measurement data for 2016 and presents a measurable assessment to the policymakers of China for streamlining their efforts on air quality improvement and O3 containment.

Overall and cause-specific mortality in the Sentinel system: A power analysis.

Mortality data within the Sentinel Death Tables remain generally uncharacterized. Assessment of mortality data within Sentinel will help inform its utility for medical product safety studies. To determine if Sentinel contains sufficient all-cause and cause-specific mortality events to power postmarketing safety studies. We calculated crude rates of all-cause mortality and suicide and proportional mortality from suicide from 2004 to 2012 in seven Sentinel data partners. Results were stratified by data partner, sex, age group, and calendar year and compared with national estimates from Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research. We performed sample size estimations for all-cause mortality and 10 leading causes of death. We observed 479694 deaths, including 5811 suicides, during 68 million person-years of follow-up. Pooled mean death and suicide rates in the data partners were 710 and 8.6 per 100000 person-years, respectively (vs 810 and 11.8 nationally). The mean proportional mortality from suicide among the data partners was 1.2%, compared with 1.5% nationally. National trends of decreasing overall mortality and increasing proportional mortality for suicide were reflected within Sentinel. We estimated that detecting hazard ratios of 1.25 and 3 would require 16442 and 460 exposed patients, respectively, for overall mortality, and 1.3 million and 37 411, respectively, for suicide. This was the first study to investigate mortality data in the Sentinel death tables. We found that all-cause mortality appeared well powered for use as a safety outcome and cause-specific mortality outcomes may be adequately powered in certain circumstances. Further investigation into the quality of the Sentinel death data is needed.

Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK

SummaryBackgroundBMI is known to be strongly associated with all-cause mortality, but few studies have been large enough to reliably examine associations between BMI and a comprehensive range of cause-specific mortality outcomes.MethodsIn this population-based cohort study, we used UK primary care data from the Clinical Practice Research Datalink (CPRD) linked to national mortality registration data and fitted adjusted Cox regression models to examine associations between BMI and all-cause mortality, and between BMI and a comprehensive range of cause-specific mortality outcomes (recorded by International Classification of Diseases, 10th revision [ICD-10] codes). We included all individuals with BMI data collected at age 16 years and older and with subsequent follow-up time available. Follow-up began at whichever was the latest of: start of CPRD research-standard follow up, the 5-year anniversary of the first BMI record, or on Jan 1, 1998 (start date for death registration data); follow-up ended at death or on March 8, 2016. Fully adjusted models were stratified by sex and adjusted for baseline age, smoking, alcohol use, diabetes, index of multiple deprivation, and calendar period. Models were fitted in both never-smokers only and the full study population. We also did an extensive range of sensitivity analyses. The expected age of death for men and women aged 40 years at baseline, by BMI category, was estimated from a Poisson model including BMI, age, and sex.Findings3 632 674 people were included in the full study population; the following results are from the analysis of never-smokers, which comprised 1 969 648 people and 188 057 deaths. BMI had a J-shaped association with overall mortality; the estimated hazard ratio per 5 kg/m2 increase in BMI was 0·81 (95% CI 0·80–0·82) below 25 kg/m2 and 1·21 (1·20–1·22) above this point. BMI was associated with all cause of death categories except for transport-related accidents, but the shape of the association varied. Most causes, including cancer, cardiovascular diseases, and respiratory diseases, had a J-shaped association with BMI, with lowest risk occurring in the range 21–25 kg/m2. For mental and behavioural, neurological, and accidental (non-transport-related) causes, BMI was inversely associated with mortality up to 24–27 kg/m2, with little association at higher BMIs; for deaths from self-harm or interpersonal violence, an inverse linear association was observed. Associations between BMI and mortality were stronger at younger ages than at older ages, and the BMI associated with lowest mortality risk was higher in older individuals than in younger individuals. Compared with individuals of healthy weight (BMI 18·5–24·9 kg/m2), life expectancy from age 40 years was 4·2 years shorter in obese (BMI ≥30·0 kg/m2) men and 3·5 years shorter in obese women, and 4·3 years shorter in underweight (BMI <18·5 kg/m2) men and 4·5 years shorter in underweight women. When smokers were included in analyses, results for most causes of death were broadly similar, although marginally stronger associations were seen among people with lower BMI, suggesting slight residual confounding by smoking.InterpretationBMI had J-shaped associations with overall mortality and most specific causes of death; for mental and behavioural, neurological, and external causes, lower BMI was associated with increased mortality risk.FundingWellcome Trust.

Propensity-score matching with competing risks in survival analysis.

Propensity‐score matching is a popular analytic method to remove the effects of confounding due to measured baseline covariates when using observational data to estimate the effects of treatment. Time‐to‐event outcomes are common in medical research. Competing risks are outcomes whose occurrence precludes the occurrence of the primary time‐to‐event outcome of interest. All non‐fatal outcomes and all cause‐specific mortality outcomes are potentially subject to competing risks. There is a paucity of guidance on the conduct of propensity‐score matching in the presence of competing risks. We describe how both relative and absolute measures of treatment effect can be obtained when using propensity‐score matching with competing risks data. Estimates of the relative effect of treatment can be obtained by using cause‐specific hazard models in the matched sample. Estimates of absolute treatment effects can be obtained by comparing cumulative incidence functions (CIFs) between matched treated and matched control subjects. We conducted a series of Monte Carlo simulations to compare the empirical type I error rate of different statistical methods for testing the equality of CIFs estimated in the matched sample. We also examined the performance of different methods to estimate the marginal subdistribution hazard ratio. We recommend that a marginal subdistribution hazard model that accounts for the within‐pair clustering of outcomes be used to test the equality of CIFs and to estimate subdistribution hazard ratios. We illustrate the described methods by using data on patients discharged from hospital with acute myocardial infarction to estimate the effect of discharge prescribing of statins on cardiovascular death.

Racial Disparity in Treatment Outcomes for Men with High-Risk Prostate Cancer in the Modern Era – A SEER-Medicare Linked Database Analysis

It is unknown whether previously reported racial disparities in prostate cancer (PCa) outcomes persist in the modern era. Prior studies have ascribed inferior outcomes in African American (AA) PCa patients to socioeconomic status (SES); while others contend that there are biological factors may explain the disparity. A limitation of studies that have relied on the Surveillance, Epidemiology, and End Results (SEER) database is that it lacks information on androgen deprivation therapy (ADT), which has been shown to improve outcomes for men with high-risk PCa treated with radiotherapy (RT). The purpose of this study is to utilize the SEER-Medicare database to examine whether a difference in outcomes persist after controlling for ADT utilization. From the SEER-Medicare database, we extracted patients with Gleason 8-10 with N0M0 PCa diagnosed from 2004 to 2013 who underwent intensity modulated RT (IMRT) with or without a brachytherapy (BT) boost, and radical prostatectomy (RP). ADT was defined as treatment with GnRH agonists (not orchiectomy or other forms of pharmacologic ADT). A total of 2,225 IMRT, 477 IMRT+BT and 158 RP patients matched our search criteria. Median follow up calculated via the reverse Kaplan-Meier method. Cause-specific mortality (CSM) was evaluated via multivariate regression using the proportional hazards model described by Fine and Gray, which accounts for other-cause mortality (OCM) as a competing risk. Median follow-up was 41 months. After adjusting for Gleason score, treatment modality, ADT status and age at diagnosis, we found no significant difference in CSM between AA men and White men (adjusted hazard ratio (AHR) 0.629, p = 0.26). After restricting RT treatment modality to IMRT only and adjusting for ADT use, we did not identify any significant racial differences in CSM amongst patients with high-risk PCa. Although the finding is hypothesis generating, the relatively short median follow-up may not rule out long-term divergence in CSM outcomes.

Deriving Small Area Mortality Estimates Using a Probabilistic Reweighting Method

Small area health estimates are important for studying environmental exposure, disease transmission, and health outcomes at the local scale. Yet, to protect privacy, the majority of publicly available health data are aggregated within larger spatial units such as states or counties. This article describes a method to generate small area mortality estimates from individual microdata that are available only for larger geographic entities. The mortality estimates are based on the probabilistic reweighting and spatial allocation of a population constructed by combining the individual-level microdata with census tract–level summary data. The generated mortality counts can be used to explore local mortality patterns and identify clusters of mortality from various causes. Validation of the allocated death counts against actual restricted-use census tract–level death counts suggests that the estimated counts reliably duplicate the total mortality patterns found in the actual data. The allocations of cause-specific mortality outcomes are less accurate, however.

Global burden of all-cause and cause-specific mortality due to smokeless tobacco use: systematic review and meta-analysis

ObjectivesTo systematically review and meta-analyse the studies investigating the association between smokeless tobacco (SLT) use and all-cause mortality and cause-specific mortality outcomes among adult users of SLT and estimate the...