Covariate-adjusted Hazard Ratio Research Articles

Patterns of cognitive domain abnormalities enhance discrimination of dementia risk prediction: The ARIC study.

The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated. We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models. Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk). By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression. Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.

Association between cardiovascular disease risk and incident type 2 diabetes mellitus in individuals with prediabetes: A retrospective cohort study

AimsIn this study, we aimed to evaluate the impact of overall cardiovascular disease (CVD) risk on the development of incident T2DM in patients with prediabetes. MethodsWe retrospectively enrolled 5,908 subjects with prediabetes who underwent health check-ups at the Asan Medical Center. CVD risk was estimated using the Framingham Risk Score (FRS). We compared moderate- to high-risk groups with low-risk controls based on the FRS. Cox proportional hazards regressions were conducted to estimate the time-to-develop incident T2DM. ResultsAmong the 5908 subjects with prediabetes, 3031 (51.8 %) were identified to have either moderate or high CVD risk scores. During a median follow-up of 5.2 years, 278 (9.2 %) patients from the moderate- to high-risk group and 171 (5.9 %) from the low-risk group were diagnosed with T2DM. The covariate-adjusted hazard ratio for the incident T2DM was 1.30 (95 % CI, 1.06–1.60, p = 0.011) in the moderate- to high-risk group compared to the low-risk controls. ConclusionAmong patients with prediabetes, those with high CVD risk were more likely to develop incident T2DM, as determined by the FRS. CVD risk factors should be properly evaluated and managed in individuals with prediabetes to reduce the risk of both incident T2DM and associated cardiovascular complications.

Overall Survival and Associations of Insurance Status Among Hispanic Men With High-Risk Prostate Cancer.

Objectives Our objectives were to (1) determine the association between ethnicity and high-risk prostate cancer (PCa) survival and (2) determine whether this association is modified by insurance status. Methods We performed a retrospective review of the National Cancer Database (NCDB) from 2004 to 2017 of non-Hispanic White (NHW), Hispanic White (HW), or Black men with high-risk PCa. A multivariate Cox regression model was built to test the association between overall survival (OS) and race/ethnicity, insurance status, and their interaction, controlling for various socioeconomic and disease-specific variables. Results A total of 94,708 men with high-risk PCa were included in the analysis. Both HW and Black men had lower socioeconomic status characteristics and lower rates of private insurance. Race/ethnicity was significantly associated with OS in the adjusted analysis. Only Medicare demonstrated significantly worse OS. NHW (covariate-adjusted hazard ratio (aHR): 1.83, 95% CI: 1.45-2.32) and Black (aHR: 1.71, 05% CI: 1.34-2.19) men demonstrated significantly worse survival when compared to HW men. Subgroup analysis demonstrated significant differences occurring among HW men with private insurance/managed care when compared to those not insured, Medicaid, Medicare, and other government insurance types. Conclusion Despite socioeconomic and demographic disadvantages, HW men demonstrate improved OS compared to NHW men. Furthermore, HW men demonstrated improved OS compared to NHW men within nearly each insurance status type. This finding is likely the result of a complex multifactorial web and as such serves as an interesting hypothesis-generating study.

The Healthy Ageing Questionnaire Index: Validation in the Singapore Longitudinal Ageing Study

Introduction: Healthy ageing (HA) indices typically use full questionnaire, performance- or blood-based assessment of functional ability which are time-consuming and resource-intensive. We developed and validated a simple and brief Healthy Ageing Questionnaire (HAQ) index with comparable measurement accuracy. Methods: The 15-item HAQ (scored 0–100) was developed using data of 500 participants in the Singapore Study of Successful Ageing (SSOSA), a sub-cohort of the Singapore Longitudinal Ageing Study (SLAS-2). Its construct, concurrent, and predictive validity were evaluated in 2,161 participants in the SLAS-2 who were non-participants of the SSOSA. Results: The HAQ index (mean = 64.0, SD = 11.8) showed a coherent 3-factor structure (Cronbach’s alpha = 0.735). HAQ scores were higher among participants who were female, highly educated, not living alone, non-smoking, non-alcohol drinkers, not at risk of malnutrition, were robust or pre-frail, not disabled, had no or <5 medical conditions, and no recent fall or hospitalization. It was positively correlated with Mini-Mental State Examination and life satisfaction, and negatively correlated with age, logMAR vision, 5 times sit-and-stand, and timed-up-and-go. The HAQ index was significantly correlated but showed modest concordance with the Rowe-Kahn SA index. Increasing HAQ index quintiles were associated with decreased mortality risks from 40.6 to 9.7 deaths per 1,000 person-years; covariate-adjusted hazard ratio for the highest Q5 levels (HAQ score >70) was 0.44 (95% CI = 0.28–0.67). Using receiver operating characteristics analysis of predictive accuracy for survival, the area under the curve of HAQ was 0.675, and Rowe-Kahn SA index was 0.660 (p = 0.361). Conclusion: The HAQ is a brief and accurate HA index that is potentially useful across diverse settings and purposes in research, healthcare, and policy-making.

PO-04-174 AN ELECTROGRAPHIC DEEP LEARNING MODEL FOR LONG-TERM MORTALITY OF THE PATIENTS SURVIVING AFTER ACUTE MYOCARDIAL INFARCTION

The diagnosis of acute myocardial infarction (AMI) initially depends on a patient’s history and the 12-lead ECG. Significant changes of the ST segment on ECG are one of the diagnostic markers of AMI and are associated with higher short-term or long-term mortality of patients. However, scoring systems or predictors for long-term risk stratification are still lacking for patients with AMI. Recently deep learning (DL) model built based on 12-lead ECG showed its great potential for early diagnosis of heart failure and atrial fibrillation. We aimed to develop a prognosis model for the long-term mortality of AMI patients based on 12-lead ECG using DL. Twelve-lead ECGs of patients during AMI were retrieved retrospectively between 2011 to 2017, and a convolutional neural network (CNN) using 12-lead ECG and patient’s age has been built to predict all-cause death within one year. The patients’ ECG recordings were split into training, validation, and testing set at a ratio of 5:2:3 and the patients were not overlapped among different datasets. Survival analysis was conducted using the Kaplan-Meier method with available follow-up data in a testing set stratified by the built model. Furthermore, Cox proportional hazard model was performed to get crude hazard ratio (HR) and covariate-adjusted HR for TIMI and GRACE score. 16827 ECGs from 2238 patients (77% male, age 64.8±13.8 years) with AMI were included. The AUC of the DL model is 0.80, with a sensitivity of 82%, and specificity of 66% using an optimal threshold on the testing set. In addition, we also found that the patients labeled as dead by DL model have a higher probability of death over a 6-year follow-up with the HR of 6.00 (95% confidence interval (CI) 3.92-9.20) while the HR of TIMI score is 1.38 (95% CI 0.97-1.97) and HR of GRACE score is 2.72 (95% CI 1.92-3.86). By applying multivariate adjustment, the DL model can be an independent predictor with the HR of 5.68 (95% CI 3.69-8.74) for the sex-adjusted model, 6.11 (95% CI 3.95-9.45) for the TIMI-socre-adjusted model and 5.22 (95% CI 3.38-8.06) for GRACE-score-adjusted model. (Figure 1) Our result showed that the DL model built based on 12-lead ECG can predict long-term mortality after AMI for up to 6 years. The DL model can provide an instant prognostic indicator using the 12-lead ECG complemented with TIMI or GRACE scores.

Vitamin D deficiency and driveline infection in patients with a left ventricular assist device implant

Driveline infection is a frequent complication in recipients of durable left ventricular assist devices (LVAD), but its cause is largely unclear. Since vitamin D supplementation can reduce the risk of infections, we aimed at investigating the association of vitamin D deficiency with driveline infection. In 154 patients with continuous flow LVAD implants, we assessed 2-year risk of driveline infection according to vitamin D status (circulating 25-hydroxyvitamin D < 25 nmol/L or ⩾25 nmol/L). Of the study cohort, 34% (n = 53) had 25-hydroxyvitamin D concentrations <25 nmol/L. Kaplan-Meir estimates of 2-year freedom from driveline infection were in the vitamin D deficient and vitamin D non-deficient groups 49.7% and 74.2%, respectively (p = 0.017). Covariate-adjusted hazard ratio of driveline infection for the vitamin D deficient versus non-deficient group was 2.51 [95% CI: 1.11-5.69; p = 0.028). Circulating concentrations of endocrine regulators of calcium and phosphorus metabolism such as parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor-23 were not significantly associated with the risk of driveline infection (p-values > 0.15). In total, our data indicate that in LVAD recipients deficient vitamin D status is a predictor of driveline infection, but future studies are needed to investigate whether these associations are causal.

High cardiovascular disease risk-associated with the incidence of Type 2 diabetes among prediabetics

BackgroundPrediabetes is a risk factor for developing Type 2 diabetes mellitus (T2D). We report on the first cohort study of the association between high cardiovascular diseases (CVD) risk with the incidence of T2D in prediabetics. First, estimate the direct effect of developing T2D on patients with prediabetes who have high CVDs risk; and 2) assess the potential increased risk of developing T2D mediated by statins. MethodsWe conducted a population-based cohort study using a subset of data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) from 2000 to 2015. Cox proportional hazards (PH) regressions were conducted to estimate our primary outcome, which is the time to T2D among patients with prediabetes. ResultsFrom the 4995 filtered prediabetic participants identified between 2000 and 2015, 2800 participants were diagnosed with high CVDs risk scores as measured by the Framingham risk score. 2195 participants were non-high CVDs risk controls. The covariate-adjusted hazard ratio (HR) of 1.24 [95% confidence interval (CI), 1.10-1.31] for T2D by CVDs risk among prediabetics was observed. The total effect of CVDs risk on developing T2D was decomposed to a natural direct effect of high CVDs risk HR= 1.18 [95% CI, 1.01-1.48] and an indirect effect through statin therapy of HR= 1.06 [95% CI, 0.97-1.30]. ConclusionPatients with prediabetes and high CVDs risk had a 24% higher chance of developing T2D. The high CVDs risk effect was mediated by statin therapy. Regular monitoring and counselling of prediabetics using statins is likely warranted to prevent the incidence of T2D.

Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts.

Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data. Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models. Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes. Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.

Abstract P176: Genes That Increase Human Lifespan By Protecting Against Risk Of Death From Cardiometabolic Diseases

Further to our FOXO3 findings last year, we asked whether other longevity gene variants work by mitigating mortality risk from aging-related diseases. In a longitudinal study, 3,584 American men of Japanese ancestry from the Kuakini Honolulu Heart Program were followed from baseline (Exam 4, 1991-93) until Dec 31, 2019 (1% of men) or death (99%). At baseline, 2,512 subjects had either diabetes (n=1,010), hypertension (n=1,919) or coronary heart disease (CHD; n=738), and 1,072 lacked any cardiometabolic diseases (CMD). DNA samples for genotyping were obtained at baseline. Genotype frequencies of SNPs in MAP3K5 , PIK3R1 , GHR, CTGF , EGFR , FLT1 , SIRT5 and SIRT7 were compared between subjects with and without ageing-related diseases . In subjects with CMD, MAP3K5 rs2076260 longevity-associated genotypes CC and CC + TT were associated with longer lifespan (covariate-adjusted hazard ratio [HR] 1.23 [95% CI: 1.12-1.35, p= 2.5x10 -5 ] in a major allele homozygote model, and 1.22 [95% CI: 1.11-1.33, p= 1.10x10 -5 ] in a heterozygote disadvantage model) compared with CT . For diabetes, hypertension and CHD, HR p -values were 0.019, 0.00048, 0.093, and 0.0024, 0.00040, 0.0014, in each respective genetic model. For PIK3R1 , subjects with cardiovascular disease (CVD) having the longevity-associated genotypes TT / CC of SNP rs7709243 had survival curves similar to those of subjects without a CVD (HR 1.26 [95% CI, 1.14-1.39; p =0.0000043]). In contrast, survival curves of subjects with the CT genotype were significantly lower compared with survival curves of subjects without a CVD ( p =0.0000012 compared with TT / CC , and p =0.0000028 compared with CT ). For GHR SNP rs4130113 , in a heterozygote disadvantage model GG vs longevity-associated AG genotype was associated with reduced mortality risk from hypertension (HR 1.23 [95% CI, 0.94-1.41; p =0.0041]). Men without CVD showed no association of longevity-associated genotype with lifespan. For each gene, men without the disease outlived men with disease ( p &lt; 10 -6 ), but genotype had no effect on lifespan. In conclusion, for MAP3K5 , PIK3R1 and GHR , but not other longevity genes, longevity genotype increases lifespan only in individuals who have CMD, CVD or hypertension, likely by protection against disease-related cellular stress.

Tuberculosis-associated depression: a population-based cohort study of people immigrating to British Columbia, Canada, 1985–2015

To estimate the risk of tuberculosis (TB)-associated depression. A second aim was to estimate the extent to which any increased risk of depression among TB patients may be mediated by the length of hospital length stay (LOS) METHODS: Retrospective cohort study of linked healthcare claims and public health surveillance data. Our primary outcome, time-to-depression, was analyzed using Cox proportional hazards (PH) regressions. Causal mediation analysis was used to estimate the natural direct and indirect effect of TB mediated by hospital LOS. Among 755,836 participants (52.2% female, median age=35 years, median follow-up=8.75 years), 2295 were diagnosed with TB (exposure), and 128,963 were diagnosed with depression (outcome). We observed a covariate-adjusted hazard ratio (aHR) of 1.24 (95% CI, 1.14-1.34) for depression by TB. The total effect of TB on depression was decomposed into a natural direct effect of TB of aHR=1.11 (95% CI, 1.02-1.21) and an indirect effect through hospital LOS of aHR=1.11 (95% CI, 1.10-1.12), indicating that TB's total effect was mediated by 50% (95% CI, 35-82%) through hospital LOS. TB patients had a 24% higher risk of developing depression. TB's effect was mediated substantially by hospital LOS, requiring further study. Depression screening among TB patients is warranted.

Association of growth hormone receptor gene variant with longevity in men is due to amelioration of increased mortality risk from hypertension.

The single nucleotide polymorphism (SNP) rs4130113 of the growth hormone receptor gene (GHR) is associated with longevity. Here we explored whether longevity-associated genotypes protect against mortality in all individuals, or only in individuals with aging-related diseases. Rs4130113 genotypes were tested for association with mortality in 3,557 elderly American men of Japanese ancestry. At baseline (1991–1993), 1,000 had diabetes, 730 had coronary heart disease (CHD), 1,901 had hypertension, 485 had cancer, and 919 lacked these diseases. The men were followed from baseline until Dec 31, 2019 or death (mean 10.8 ± 6.5 SD years, range 0.01–28.8 years; 99.0% deceased by that date). In a heterozygote disadvantage model, longevity-associated genotypes were associated with significantly lower mortality risk in individuals having hypertension (covariate-adjusted hazard ratio [HR] 0.83 [95% CI: 0.76–0.93, p = 4.3 x10–4]. But in individuals with diabetes, CHD, and cancer there was no genotypic difference in lifespan. As expected, normotensive men outlived men with hypertension (p = 0.036). There was no effect, however, of genotypic difference on lifespan in normotensive men (p = 0.11). We found that SNP rs4130113 potentially influenced the binding of transcription factors E2A, MYF, NRSF, TAL1, and TCF12 so as to alter GHR expression. We propose that in individuals with hypertension, longevity-associated genetic variation in GHR enhances cell resilience mechanisms to help protect against cellular stress caused by hypertension. As a result, hypertension-affected men who possess the longevity-associated genetic variant of GHR live as long as normotensive men.

Black Race Is Associated With Higher Rates of Early-Onset End-Stage Renal Disease and Increased Mortality Following Liver Transplantation.

Black race is a risk factor for end-stage renal disease (ESRD). Racial disparities in the risks of early and long-term renal complications after liver transplantation (LT) have not been systematically studied. This study evaluated racial differences in the natural history of acute and chronic renal insufficiency after LT. This was a retrospective single-center cohort study of 763 non-Hispanic White and 181 Black LT recipients between 2008 and 2017. Black race was investigated as an independent predictor of the following outcomes: (1) receipt and duration of early post-LT hemodialysis and (2) time to post-LT ESRD. The interaction of race and post-LT ESRD on survival was also studied. Black recipients had higher rates of pre-LT hypertension (P<0.001), but diabetes mellitus and renal function before LT were not different by race (all P>0.05). Overall, 15.2% of patients required early hemodialysis immediately after LT with no difference by race (covariate-adjusted odds ratio, 0.89; P=0.71). Early dialysis discontinuation was lower among Black recipients (covariate-adjusted hazard ratio [aHR], 0.47; P=0.02), whereas their rate of post-LT ESRD was higher (aHR, 1.91; P=0.005). Post-LT survival after ESRD was markedly worse for Black (aHR, 11.18; P<0.001) versus White recipients (aHR, 5.83; P<0.001; interaction P=0.08). Although Black and White LT recipients had comparable pretransplant renal function, post-LT renal outcomes differed considerably, and the impact of ESRD on post-LT survival was greater for Black recipients. This study highlights the need for an individualized approach to post-LT management to improve outcomes for all patients.

Association of aldosterone and blood pressure with the risk for cardiovascular events after treatments in primary aldosteronism

Background and aimsWe used a dataset from a Japanese nationwide registry of patients with primary aldosteronism, to determine which of the parameters of hyperaldosteronism and blood pressure before or after treatments for primary aldosteronism (i.e., surgical adrenalectomy or a medication treatment) are important in terms of cardiovascular prognosis. MethodsWe assessed whether plasma aldosterone-to-renin ratio and pulse pressure levels before treatment and 6 months after treatment were associated with composite cardiovascular disease events during the 5-year follow-up period. ResultsThe cohort included 1987 patients (mean age was 53.2 years, 52.0% were female, 37.2% had undergone surgical treatment, and the remainder had been treated with mineralocorticoid receptor antagonists). In the Cox proportional hazard model, the covariate-adjusted hazard ratio (95% confidence interval) for the composite cardiovascular disease events risk for each one-standard-deviation increase in the aldosterone-to-renin ratio or pulse pressure before treatment, those after treatment, or the duration of hypertension were 1.24 (1.05, 1.48), 0.74 (0.54, 1.02), and 1.07 (0.79, 1.44), 1.43 (1.07, 1.92), and 1.52 (1.19, 1.95), respectively. Patients with a high pre-treatment aldosterone-to-renin ratio of more than 603 and a large post-treatment pulse pressure of more than 49 mmHg showed approximately three-fold higher hazard ratios for cardiovascular events risk compared to those with a lower aldosterone-to-renin ratio and smaller pulse pressure. ConclusionsHigher aldosterone-to-renin ratio before treatments, higher pulse pressure after treatments, and longer duration of hypertension were prognostic factors for cardiovascular diseases. Early intervention may be important for preventing cardiovascular disease among patients with primary aldosteronism.

Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 (MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease.

Genetic variants of the kinase signaling gene MAP3K5 are associated with longevity. Here we explore whether the longevity-association involves protection against mortality in all individuals, or only in individuals with aging-related diseases. We tested the strongest longevity associated single nucleotide polymorphism (SNP), rs2076260, for association with mortality in 3,516 elderly American men of Japanese ancestry. At baseline (1991–1993), 2,461 had either diabetes (n=990), coronary heart disease (CHD; n=724), or hypertension (n=1,877), and 1,055 lacked any of these cardiometabolic diseases (CMDs). The men were followed from baseline until Dec 31, 2019. Longevity-associated genotype CC in a major allele homozygote model, and CC+TT in a heterozygote disadvantage model were associated with longer lifespan in individuals having a CMD (covariate-adjusted hazard ratio [HR] 1.23 [95% CI: 1.12–1.35, p=2.5x10–5] in major allele homozygote model, and 1.22 [95% CI: 1.11–1.33, p=1.10x10–5] in heterozygote disadvantage model). For diabetes, hypertension and CHD, HR p-values were 0.019, 0.00048, 0.093, and 0.0024, 0.00040, 0.0014, in each respective genetic model. As expected, men without a CMD outlived men with a CMD (p=1.9x10–6). There was, however, no difference in lifespan by genotype in men without a CMD (p=0.21 and 0.86, respectively, in each genetic model). In conclusion, we propose that in individuals with a cardiometabolic disease, longevity-associated genetic variation in MAP3K5 enhances resilience mechanisms in cells and tissues to help protect against cardiometabolic stress caused by CMDs. As a result, men with CMD having longevity genotype live as long as all men without a CMD.

Post-tuberculosis airway disease: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015.

BackgroundCurrent epidemiological evidence of post-TB airway disease is largely cross-sectional and derived from high-TB-incidence settings. We present the first cohort study of post-TB airway disease in a low-TB-incidence setting.Aims(1) analyze the risk of airway disease by respiratory TB, (2) assess potential unmeasured confounding between TB and airway disease, and (3) investigate TB effect measure modification.MethodsA population-based cohort study using healthcare claims data for immigrants to British Columbia (BC), Canada, 1985–2015. Airway disease included chronic airway obstruction, asthma, bronchitis, bronchiolitis, and emphysema. Respiratory TB was defined from TB registry data. Cox proportional hazards (PH) regressions were used to analyze time-to-airway disease by respiratory TB. Sensitivity analyses included varying definitions of TB and airway disease. Potential unmeasured confounding by smoking was evaluated by E-value and hybrid least absolute shrinkage and selection operator (LASSO)-high-dimensional propensity score (hdPS).FindingsIn our cohort (N = 1 005 328; nTB=1141) there were 116 840 incident cases of airway disease during our 30-year study period (10.43 per 1,000 person-years of follow-up), with cumulative incidence of 42·5% among respiratory TB patients compared with 11·6% among non-TB controls. The covariate-adjusted hazard ratio (aHR) for airway disease by respiratory TB was 2·08 (95% CI: 1·91–2·28) with E-value=3·58. The LASSO-hdPS analysis produced aHR=2·26 (95% CI: 2·07–2·47).InterpretationA twofold higher risk of airway disease was observed among immigrants diagnosed with respiratory TB, compared with non-TB controls, in a low-TB-incidence setting. Unmeasured confounding is unlikely to explain this relationship. Models of post-TB care are needed.FundingCanadian Institutes of Health Research.

Post-tuberculosis mortality risk among immigrants to British Columbia, Canada, 1985-2015: a time-dependent Cox regression analysis of linked immigration, public health, and vital statistics data.

To compare non-tuberculosis (non-TB)-cause mortality risk overall and cause-specific mortality risks within the immigrant population of British Columbia (BC) with and without TB diagnosis through time-dependent Cox regressions. All people immigrating to BC during 1985-2015 (N = 1,030,873) were included with n = 2435TB patients, and the remaining as non-TB controls. Outcomes were time-to-mortality for all non-TB causes, respiratory diseases, cardiovascular diseases, cancers, and injuries/poisonings, and wereascertained using ICD-coded vital statistics data. Cox regressions were used, with a time-varying exposure variable for TB diagnosis. The non-TB-cause mortality hazard ratio (HR) was 4.01 (95% CI 3.57-4.51) with covariate-adjusted HR of 1.69 (95% CI 1.50-1.91). Cause-specific covariate-adjusted mortality risk was elevated for respiratory diseases (aHR = 2.96; 95% CI 2.18-4.00), cardiovascular diseases (aHR = 1.63; 95% CI 1.32-2.02), cancers (aHR = 1.40; 95% CI 1.13-1.75), and injuries/poisonings (aHR = 1.85; 95% CI 1.25-2.72). In any given year, if an immigrant to BC was diagnosed with TB, their risk of non-TB mortality was 69% higher than if they were not diagnosed with TB. Healthcare providers should consider multiple potential threats to the long-term health of TB patients during and after TB treatment. TB guidelines in high-income settings should address TB survivor health.

Real-world behavior of CRT pacing using the AdaptivCRT algorithm on patient outcomes: Effect on mortality and atrial fibrillation incidence.

BackgroundThe AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular conduction, providing synchronized left ventricular pacing in patients with normal PR interval and adaptive BiV pacing in patients with prolonged PR interval. Previous analyses demonstrated an association between aCRT and clinical benefit. We evaluated the incidence of patient mortality and atrial fibrillation (AF) with aCRT compared with standard CRT in a real‐world population.Methods and ResultsPatients enrolled in the Medtronic Personalized CRT Registry and implanted with a CRT from 2013‐2018 were divided into aCRT ON or standard CRT groups based upon device‐stored data. A Frailty survival model was used to evaluate the potential survival benefit of aCRT, accounting for patient heterogeneity and center variability. Daily AF burden and first device‐detected AF episodes of various durations were recorded by the device during follow‐up.A total of 1814 CRT patients with no reported long‐standing AF history at implant were included. Mean follow‐up time was 26.1 ± 16.5 months and 1162 patients (64.1%) had aCRT ON. Patient survival probability at 36 months was 88.3% for aCRT ON and 83.7% for standard CRT (covariate‐adjusted hazard ratio [HR] = 0.71, 95% CI: 0.53‐0.96, P = .028). Mean AF burden during follow‐up was consistently lower in aCRT ON patients compared with standard CRT. At 36 months, the probability of AF was lower in patients with aCRT ON, regardless of which AF definition threshold was applied (6 minutes‐30 days, all P < .001).ConclusionUse of the AdaptivCRT algorithm was associated with improved patient survival and lower incidence of AF in a real‐world, prospective, nonrandomized registry.

The bidirectional association between type 2 diabetes and psoriasis: Two retrospective cohort studies.

Inflammation plays a crucial role in both type 2 diabetes mellitus (T2DM) and psoriasis pathogenesis; thus, a bidirectional association between them is likely suspected. We investigated the possible bidirectional association between T2DM and psoriasis. Using the Taiwan National Health Insurance Research Database, we conducted two retrospective cohort studies. The analysis of psoriasis onset in relation to T2DM status included 31,697 patients with diabetes and 126,788 nondiabetic control subjects (Analysis 1). The analysis of T2DM onset in relation to psoriasis status included 1,947 psoriatic patients and 7,788 nonpsoriatic control subjects (Analysis 2). The follow-up period was from 2000 to the date of the outcome of interest, date of death, or December 31, 2013. Cox proportional models were used to estimate the relative hazards. In Analysis 1, Kaplan-Meier (KM)-based cumulative incidence of psoriasis was higher in the T2DM cohort than that in the non-T2DM cohort (1.2% vs. 0.7%). The covariate-adjusted hazard ratio (HR) was 1.40 [95% confidence interval (CI), 1.20-1.63] for patients with T2DM. Analysis 2 revealed KM-based cumulative T2DM incidences of 18.7% and 13.1% in psoriatic and nonpsoriatic subjects, respectively. The adjusted HR for incident T2DM was higher in patients with psoriasis (1.38; 95% CI, 1.20-1.58). This article may not represent the population worldwide and patient selection bias may exist. Our results provide evidence for a bidirectional T2DM-psoriasis association. T2DM and psoriasis are common worldwide; thus, our findings have public health implications for the early identification and management of these comorbid diseases.

Dipeptidyl peptidase-4 inhibitor use is associated with decreased risk of fracture in patients with type 2 diabetes: a population-based cohort study.

The aim of this study was to investigate the putative link between dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of fracture in patients with type 2 diabetes. This propensity-score-matched population-based cohort study was performed between 2009 and 2013 on patients with type 2 diabetes who were stable metformin users. A total of 3996 patients with type 2 diabetes used DPP-4i as a second-line antidiabetic drug. The same number of matched non-DPP-4i users were followed up until fracture occurrence, health insurance policy termination, or the end of 2013. The incidence rates of overall and cause-specific fractures were estimated based on the Poisson assumption. A multiple Cox proportional hazard model was used to estimate the covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) to determine the association between DPP-4i use and overall and cause-specific fractures stratified by age and sex. Over a maximum follow-up period of 5 years, 340 DPP-4i users and 419 non-DPP-4i users were newly diagnosed with fractures, yielding incidence rates of 28.03 and 32.04 per 1000 people per year, respectively. The Cox proportional hazard model revealed that DPP-4i use significantly reduced the risk of all-cause fractures and upper extremity fractures, with adjusted HRs of 0.86 (95% CI: 0.74-0.99) and 0.75 (95% CI: 0.59-0.95), respectively. The aforementioned associations of DDP-4i use with fracture were sustained across sex and age stratifications. The results of this study supported the premise that DPP-4i usage is associated with a reduced risk of all-cause fractures and upper extremity fractures in patients with type 2 diabetes.

Bone Health and Survival in Women With Multiple Myeloma

BackgroundMultiple myeloma (MM) is a disease of aging adults resulting in osteolytic and/or osteoporotic bone disease. Primary osteoporosis is also highly prevalent in aging adults and is associated with increased mortality. It is unknown how concurrent osteoporosis is associated with outcomes in patients who develop MM. Patients and MethodsWe identified 362 women with MM of the 161,808 enrolled in the Women’s Health Initiative (WHI) dataset and evaluated bone health using the Fracture Risk Assessment Tool (FRAX) to identify clinical factors that affect overall MM survival in post-menopausal women, as measured from the time of diagnosis. ResultsOf the 362 participants who developed incident MM, with an average 10.5 years of follow-up, 226 died, including 71 with high FRAX scores and 155 with low FRAX scores. On average, women with high FRAX scores were 8.3 years older at enrollment (95% confidence interval [CI], 7.2-9.3 years) and 8.0 years older at time of MM diagnosis (95% CI, 7.0-9.2 years) compared with those with low FRAX scores. MM mortality for women with high FRAX scores was greater (covariate-adjusted hazard ratio scores [aHR] 1.51; 95% CI, 1.01-2.25; P = .044) compared with those with low FRAX scores. ConclusionHigher fracture risk, measured by FRAX, was associated with higher MM mortality in post-menopausal women, independent of many other clinical factors.