Propensity Score-matched Cox Proportional Hazards Research Articles

Benzodiazepine use and incident risk of sudden cardiac arrest in patients with cardiovascular diseases.

Benzodiazepines (BZDs) are commonly prescribed as adjunctive drugs for patients with cardiovascular diseases (CVDs), particularly those who experience anxiety or insomnia. However, the relationship between the use of BZDs and incident risk of sudden cardiac arrest (SCA) has not been well investigated. In this study, we aimed to examine the association between the use of BZDs and the incident risk of SCA among patients with CVD. In this retrospective cohort study, a total of 74,715 eligible patients with new-onset CVD as a primary cause of hospitalization between July 2016 and August 2022 were included from the health information platform in Shenzhen, China. Among them, 61,761 BZD non-initiators were identified and matched to 12,954 BZD initiators by propensity score at a maximum ratio of 5:1. Propensity score-matched Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Over a 12-month follow-up period, 29 (2.24 per 1000 person-years) and 137 (2.22 per 1000 person-years) SCA cases occurred among propensity score-matched BZD initiators and non-initiators, respectively. Patients who initiated BZD treatment were associated with a 101% increased risk of SCA incidence compared with patients without BZD treatment (adjusted HR: 2.01, 95% CI: 1.42, 2.83). Furthermore, compared with the non-use (0 defined daily dose, DDD), the adjusted HR was 1.43 (95% CI: 1.32, 1.56) for the BZD consumption of ≤1 DDD and 2.58 (95% CI: 2.37, 2.81) for the BZD consumption of >1 DDD (P for trend < 0.001) within a 12-month follow-up period. This study provides evidence that BZD initiation may be associated with an increased incident risk of SCA in patients with CVD. Our finding highlights the importance of cautious prescribing BZDs in the health management of patients with CVD.

Association of Regular Opioid Use With Incident Dementia and Neuroimaging Markers of Brain Health in Chronic Pain Patients: Analysis of UK Biobank

ObjectivesWe aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DesignThe primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. Setting and ParticipantsDementia-free UK Biobank participants with chronic pain and regular analgesic use. MeasurementsChronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. ResultsProspective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08–1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19–0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07–1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08–1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23–1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. ConclusionRegular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.

Is There a Difference in the Incidence of Depression between Radiation and Surgical Treatments in Patients with Prostate Cancer?

Patients with cancer have a high risk of depression. However, a few studies have assessed differences in the incidence of depression among patients with prostate cancer (PC) based on whether they received radiotherapy (RTx) or surgical treatment. We analyzed data from the National Health Insurance Sharing Service database regarding the entire Korean adult population with PC (n=210,924) between 2007 and 2017. The adjusted hazard ratios (HRs) of depression associated with treatment were estimated using propensity score-matched Cox proportional hazards models and Kaplan-Meier survival analyses. Our final cohort comprised 9,456 patients with PC; of which, 8,050 men underwent surgery. During a mean follow-up duration of 7.1 years, 503 (5.3%) patients were newly diagnosed with depression. A significant difference in the incidence of depression was noted between the RTx and surgery groups (RTx vs. surgery: 5.55% vs. 5.28%; p=0.011) in the unmatched cohort. In the matched cohort, older age (≥70 years, HR: 1.596, p<0.001) and poor Charlson comorbidity index scores (HR: 1.232, p=0.039) were correlated with the risk of depression. In addition, the adjusted HR for depression in the surgery group was 0.843 (p=0.221) compared with that in the RTx group. Kaplan-Meier analyses revealed that no significant difference in the cumulative probability of persistent depression was detected between the RTx and surgery groups in matched cohort (p=0.3386). In this nationwide population-based study, no significant differences in the risk of depression were observed between the surgical and RTx groups.

MP77-19 IS ANDROGEN DEPRIVATION THERAPY ASSOCIATED WITH CEREBRAL INFARCTION IN PATIENTS WITH PROSTATE CANCER? A KOREAN NATIONWIDE POPULATION-BASED PROPENSITY SCORE MATCHING STUDY

You have accessJournal of UrologyCME1 Apr 2023MP77-19 IS ANDROGEN DEPRIVATION THERAPY ASSOCIATED WITH CEREBRAL INFARCTION IN PATIENTS WITH PROSTATE CANCER? A KOREAN NATIONWIDE POPULATION-BASED PROPENSITY SCORE MATCHING STUDY Bum Sik Tae, Jung Wan Yoo, Hoon Choi, Jae Hyun Bae, and Jae Young Park Bum Sik TaeBum Sik Tae More articles by this author , Jung Wan YooJung Wan Yoo More articles by this author , Hoon ChoiHoon Choi More articles by this author , Jae Hyun BaeJae Hyun Bae More articles by this author , and Jae Young ParkJae Young Park More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies have suggested that androgen deprivation therapy (ADT) is associated with cerebral infarction. However, conflicting results have been reported by other researchers. The aim of the present study was to evaluate the association between ADT and cerebral infarction in patients with prostate cancer (PC) using big data. METHODS: Using information from the National Health Insurance Service database representative of the entire Korean adult PC population (n=206,735), data regarding ADT and cerebral infarction between 2009 and 2016 were analyzed. Adjusted hazard ratios for cerebral infarction associated with ADT were estimated using propensity score-matched Cox proportional hazards models and Kaplan-Meier survival analyses. RESULTS: The final cohort comprised 36,146 individuals with PC, including 24,069 men (66.6%) who underwent ADT. During the mean follow-up of 4.1 years, 2792 patients were newly diagnosed with cerebral infarction. In the unmatched cohort, there was a significant difference in the annual incidence of cerebral infarction between the ADT and non-ADT groups (22.8 versus [vs] 14.6 per 1000 person-years, respectively). However, there was no significant difference between the ADT and non-ADT groups in the matched cohort (14.9 vs 14.6 per 1000 person-years). The adjusted hazard ratio for cerebral infarction for PC patients who underwent ADT was 1.045 (95% CI 0.943–1.159; p=0.401) compared with those who did not undergo ADT. In addition, the cumulative duration of ADT was also not associated with an increased risk for cerebral infarction. However, older age, hypertension, diabetes, myocardial infarction, congestive heart failure, peripheral vascular disease, renal disease, dementia, and atrial fibrillation were revealed to be factors contributing to cerebral infarction. CONCLUSIONS: This nationwide population-based study revealed that ADT was not associated with cerebral infarction after adjusting for potential confounders. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1109 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bum Sik Tae More articles by this author Jung Wan Yoo More articles by this author Hoon Choi More articles by this author Jae Hyun Bae More articles by this author Jae Young Park More articles by this author Expand All Advertisement PDF downloadLoading ...

Survival outcomes of patients with nonsmall cell lung cancer concomitantly receiving proton pump inhibitors and immune checkpoint inhibitors.

Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs], 1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR=1.64; 95% CI=1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR=2.72; 95% CI=1.54-4.78; Pinteraction = .048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs.

Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study.

Recent studies reported conflicting results on the association of androgen deprivation therapy (ADT) with dementia and Parkinson's disease in patients with prostate cancer (Pca). Therefore, this study aimed to investigate whether use of gonadotropin-releasing hormone agonist (GnRHa) increases the risk of both diseases. A nationwide population cohort study was conducted involving newly diagnosed patients with Pca %who started ADT with GnRHa (GnRHa users, n = 3,201) and control (nonusers, n = 4,123) between January 1, 2012, and December 31, 2016, using data from the National Health Insurance Service. To validate the result, a hospital cohort of patients with Pca consisting of GnRHa users (n = 205) and nonusers (n = 479) in a tertiary referral center from January 1, 2006 to December 31, 2016, were also analyzed. Traditional and propensity score-matched Cox proportional hazards models were used to estimate the effects of ADT on the risk of dementia and Parkinson's disease. In univariable analysis, risk of dementia was associated with GnRHa use in both nationwide and hospital validation cohort (hazard ratio [HR], 1.696; 95% CI, 1.425-2.019, and HR, 1.352; 95% CI, 1.089-1.987, respectively). In a nationwide cohort, ADT was not associated with dementia in both traditional and propensity score-matched multivariable analysis, whereas in a hospital validation cohort, ADT was associated with dementia only in unmatched analysis (HR, 1.203; 95% CI, 1.021-1.859) but not in propensity score-matched analysis. ADT was not associated with Parkinson's disease in either nationwide and validation cohorts. This population-based study suggests that the association between GnRHa use as ADT and increased risk of dementia or Parkinson's disease is not clear, which was also verified in a hospital validation cohort.

Abstract P2-14-07: Association between initiation of adjuvant chemotherapy beyond 30 days following surgery and overall survival among patients with triple-negative breast cancer

Abstract Background: The optimal time between surgery and initiation of adjuvant chemotherapy is unknown, though delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies have suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted particularly in high-risk triple-negative breast cancer (TNBC) patients. Objective: To determine the extent to which TTC beyond 30 days is associated with reduced overall survival (OS) in TNBC patients. Methods: Using the population-based nationwide Netherlands Cancer Registry we identified TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy. We distinguished between patients who underwent breast-conserving surgery (BCS) versus mastectomy given the difference in preoperative characteristics and outcomes. Median (95% confidence interval) follow-up was 82.9 (80.5-86.5) and 81.4 (79.5-83.9) months, respectively. Main outcomes and measures: The association between TTC beyond 30 days and OS was estimated with hazard ratios (HR) using propensity-score matched Cox proportional hazard analyses separately for patients who underwent BCS and mastectomy. Results: In total, 3016 patients were included, of whom 1079 (35.8%) underwent BCS and 1937 (64.2%) underwent a mastectomy. In matched patients who underwent BCS, 10-year OS was significantly better for patients with TTC within 30 days compared to patients with TTC beyond 30 days (84.4% vs. 76.9%, P=0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22-2.34), P=0.002). In matched patients who underwent mastectomy, there was no difference in 10-year OS between those with TTC within or beyond 30 days (74.5% vs. 74.7%, P=0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95%-CI 0.84-1.28), P=0.716). In both populations, the associations were independent of adjuvant radiotherapy. Conclusions: The current results suggest that initiation of chemotherapy beyond 30 days is associated with decreased OS in TNBC patients who underwent BCS; no association was observed for patients who underwent a mastectomy. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted. Citation Format: Erik Heeg, Perla J. Marang-van de Mheen, Marissa C. Van Maaren, Kay Schreuder, Rob A.E.M. Tollenaar, Sabine Siesling, Monique E.M.M. Bos, Marie-Jeanne T.F.D. Vrancken Peeters. Association between initiation of adjuvant chemotherapy beyond 30 days following surgery and overall survival among patients with triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-07.

Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk. To test the hypothesis that, among patients with nonvalvular AF, use of DOACs vs warfarin is associated with lower risk of incident fracture. This comparative effectiveness cohort study used the MarketScan administrative claims databases to identify patients with nonvalvular AF and who were prescribed oral anticoagulants from January 1, 2010, through September 30, 2015. To reduce confounding, patients were matched on age, sex, CHA2DS2-VASc (congestive heart failure, hypertension, age [>65 years = 1 point; >75 years = 2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The final analysis included 167 275 patients with AF. Data were analyzed from February 27, 2019 to September 18, 2019. Warfarin and DOACs (dabigatran etexilate, rivaroxaban, and apixaban). Incident hip fracture, fracture requiring hospitalization, and all clinical fractures (identified using inpatient or outpatient claims) defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. In the study population of 167 275 patients with AF (38.0% women and 62.0% men; mean [SD] age, 68.9 [12.5] years), a total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months. In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98), whereas the association with hip fractures (HR, 0.91; 95% CI, 0.78-1.07) was not statistically significant. When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67 [95% CI, 0.45-0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47-0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75-0.98]). In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis. In this real-world population of 167 275 patients with AF, use of DOACs-particularly apixaban-compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture.

Correlation of Androgen Deprivation Therapy with Cognitive Dysfunction in Patients with Prostate Cancer: A Nationwide Population-Based Study Using the National Health Insurance Service Database.

PurposeThe purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction.Materials and MethodsUsing the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT.ResultsDuring a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age (≥ 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001).ConclusionOur results revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.

Risk of All-Cause Mortality in Diabetic Patients Taking β-Blockers

ObjectiveTo assess the relationship between use of β-blockers and all-cause mortality in patients with and without diabetes. Patients and MethodsUsing data from the US National Health and Nutrition Examination Survey 1999-2010, we conducted a prospective cohort study. The study participants were followed-up from the survey participation date until December 31, 2011. We used a Cox proportional hazards model for all-cause mortality analysis. The multivariate-adjusted hazard ratios (HRs) of the participants taking β-blockers were compared with those of the participants not taking β-blockers. ResultsThis study included 2840 diabetic participants and 14,684 nondiabetic participants. Compared with diabetic participants not taking a β-blocker, all-cause mortality was significantly higher in diabetic participants taking any β-blocker (HR, 1.49; 95% CI, 1.09-2.04; P=.01), taking a β1-selective β-blocker (HR, 1.60; 95% CI, 1.13-2.24; P=.007), or taking a specific β-blocker (bisoprolol, metoprolol, and carvedilol) (HR, 1.55; 95% CI, 1.09-2.21; P=.01). In addition, all-cause mortality in diabetic participants with coronary heart disease (CHD) was significantly higher in those taking beta-blockers, compared with those not taking beta-blockers (HR, 1.64; 95% CI, 1.08-2.48; P=.02), whereas that in non-diabetic participants with CHD was significantly lower in those taking beta-blockers (HR, 0.68; 95% CI, 0.50-0.94; P=.02). A propensity score–matched Cox proportional hazards model yielded similar results. ConclusionUse of β-blockers may be associated with an increased risk of mortality for patients with diabetes and among the subset who have CHD.

Association of Higher Daptomycin Dose (7mg/kg or Greater) with Improved Survival in Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

Current guidelines recommend higher daptomycin doses than the daptomycin label dose of 6mg/kg for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia; however, the evidence supporting this recommendation is from invitro and case series studies. This study evaluated the comparative effectiveness of the daptomycin label dose versus higher daptomycin doses in patients with MRSA bacteremia. Retrospective national cohort study. Veterans Affairs medical centers. A total of 371 adults with MRSA bacteremia who were admitted between 2002 and 2015 and treated initially with vancomycin within 24hours of initial culture collection and then switched to daptomycin therapy within 7days; 138 patients (37.2%) received daptomycin doses higher than the daptomycin label dose (7mg/kg or greater), and 233 (62.8%) received the daptomycin label dose (6mg/kg). Clinical outcomes were compared among those who received the daptomycin label dose and those who received the higher dose using propensity score-matched Cox proportional hazards regression models. To identify dose partitioning associated with optimal survival, classification and regression tree (CART) analysis was used among patients, controlling for confounding with a 30-day mortality disease risk score. Propensity score-matched 30-day mortality was 8.6% (6/70 patients) among the higher dose group versus 18.6% (13/70 patients) among the label dose group (hazard ratio 0.31, 95% confidence interval 0.10-0.94). No significant differences were observed in inpatient mortality, length of stay, 30-day readmission, or 30-day S. aureus reinfection between groups. CART analysis resulted in doses of 7mg/kg or greater providing benefit only among patients with higher (more than 51%) predicted probabilities of 30-day mortality (p<0.001). To our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (7mg/kg or greater) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia.

Antibiotic Utilization and the Role of Suspected and Diagnosed Mosquito-borne Illness Among Adults and Children With Acute Febrile Illness in Pune, India.

Antibiotic resistance mechanisms originating in low- and middle- income countries are among the most common worldwide. Reducing unnecessary antibiotic use in India, the world's largest antibiotic consumer, is crucial to control antimicrobial resistance globally. Limited data describing factors influencing Indian clinicians to start or stop antibiotics are available. Febrile adults and children admitted to a public tertiary care hospital in Pune, India, were enrolled. Antibiotic usage and clinical history were recorded. Immunoassays for mosquito-borne disease and bacterial cultures were performed by protocol and clinician-directed testing. Clinical factors were assessed for association with empiric antibiotic initiation and discontinuation by day 5 using multivariable logistic regression and propensity score-matched Cox proportional hazard models. Among 1486 participants, 683 (82%) adults and 614 (94%) children received empiric antibiotics. Participants suspected of having mosquito-borne disease were less likely to receive empiric antibiotics (adjusted odds ratio [AOR], 0.5; 95% confidence interval [CI], .4-.8). Empiric antibiotics were discontinued in 450 (35%) participants by day 5. Dengue or malaria testing performed before day 4 was positive in 162 (12%) participants, and was associated with antibiotic discontinuation (AOR, 1.7; 95% CI, 1.2-2.4). In a propensity score-matched model accounting for admission suspicion of mosquito-borne disease, positive dengue or malaria tests increased hazard of antibiotic discontinuation (hazard ratio, 1.6; 95% CI, 1.2-2.0). Most patients with acute febrile illness in an Indian public hospital setting receive empiric antibiotics. Mosquito-borne disease identification is associated with reduced empiric antibiotic use and faster antibiotic discontinuation.

Evidence To Support Continuation of Statin Therapy in Patients with Staphylococcus aureus Bacteremia.

In addition to cholesterol-lowering capabilities, statins possess anti-inflammatory and immunomodulatory effects. We sought to quantify the real-world impact of different statin exposure patterns on clinical outcomes in Staphylococcus aureus bacteremia. We conducted a retrospective cohort study among hospitalized patients with positive S. aureus blood cultures receiving appropriate antibiotics within 48 h of culture collection (Veterans Affairs hospitals, 2002 to 2013). Three statin exposure groups were compared to nonusers: pretreated statin users initiating therapy in the 30 days prior to culture and either (i) continuing statin therapy after culture or (ii) not continuing after culture, and (iii) de novo users initiating at culture. Nonusers included patients without statins in the year prior to culture through discharge. Propensity score-matched Cox proportional hazards regression models were developed. We were able to balance significantly different baseline characteristics using propensity score matching for pretreated without continuation (n = 331), pretreated with continuation (n = 141), and de novo (n = 177) statin users compared to nonusers. We observed a significantly lower 30-day mortality rate (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.25 to 0.84; number needed to treat [NNT], 10) among pretreated and continued statin users, while protective effects were not observed in de novo (HR, 1.04; 95% CI, 0.60 to 1.82; NNT, undefined) or pretreated but not continued (HR, 0.92; 95% CI, 0.64 to 1.32; NNT, 47) users. In our national cohort study among patients with S. aureus bacteremia, continuation of statin therapy among incident statin users was associated with significant beneficial effects on mortality, including a 54% lower 30-day mortality rate.

The association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillation

The utility of anticoagulants for ischemic stroke prophylaxis in elderly patients with chronic kidney disease (CKD) and atrial fibrillation remains uncertain. In this population-based retrospective cohort study, we determined the association of anticoagulant use with ischemic stroke or hemorrhage in elderly patients (66 years and older) with advanced chronic kidney disease (eGFR under 45 ml/min/1.73m2) and atrial fibrillation. We followed 6,544 patients with CKD and new onset atrial fibrillation, of whom 1,475 filled a prescription for an anticoagulant. We used propensity-score matched Cox proportional hazards and competing risk models to determine the time to first event of ischemic stroke, hemorrhage or mortality. After matching to examine exposure to anticoagulants, 1,417 matched pairs were identified. The crude rate of ischemic stroke and hemorrhage were 41.3 and 61.3 with anticoagulants and 34.4 and 34.3 without anticoagulants per 100 person-years, respectively. The hazard ratios of ischemic stroke, hemorrhage, and mortality for receipt of an anticoagulation prescription were 1.10 (95% confidence interval, 0.78-1.56), 1.42 (1.04-1.93), and 0.74 (0.62-0.88) as compared to non-receipt of anticoagulation. After accounting for the competing risk of death, the hazard ratios for ischemic stroke and hemorrhage were 1.12 (0.90-1.39) and 1.60 (1.31-1.97), respectively. The findings were consistent in a sensitivity analysis accounting for time varying anticoagulant exposure. Thus, in older patients with CKD and atrial fibrillation, receipt of an anticoagulant was not associated with a lower risk of ischemic stroke, but a higher risk of hemorrhage and a lower risk of mortality.

Association Between Androgen Deprivation Therapy and Risk of Dementia

ImportanceA growing body of evidence supports a link between androgen deprivation therapy (ADT) and cognitive dysfunction, including Alzheimer disease. However, it is currently unknown whether ADT may contribute to the risk of dementia more broadly.ObjectiveTo use an informatics approach to examine the association of ADT as a treatment for prostate cancer with the subsequent development of dementia (eg, senile dementia, vascular dementia, frontotemporal dementia, and Alzheimer dementia).Design, Setting, and ParticipantsIn this cohort study, a text-processing method was used to analyze electronic medical record data from an academic medical center from 1994 to 2013, with a median follow-up of 3.4 years (interquartile range, 1.0-7.2 years). We identified 9455 individuals with prostate cancer who were 18 years or older at diagnosis with data recorded in the electronic health record and follow-up after diagnosis. We excluded 183 patients with a previous diagnosis of dementia. Our final cohort comprised 9272 individuals with prostate cancer, including 1826 men (19.7%) who received ADT.Main Outcomes and MeasuresWe tested the effect of ADT on the risk of dementia using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis.ResultsAmong 9272 men with prostate cancer (mean [SD] age, 66.9 [10.9] years; 5450 [58.8%] white), there was a statistically significant association between use of ADT and risk of dementia (hazard ratio, 2.17; 95% CI, 1.58-2.99; P < .001). In sensitivity analyses, results were similar when excluding patients with Alzheimer disease (hazard ratio, 2.32; 95% CI, 1.73-3.12; P < .001). The absolute increased risk of developing dementia among those who received ADT was 4.4% at 5 years (7.9% among those who received ADT vs 3.5% in those who did not receive ADT). Analyses stratified by duration of ADT found that individuals with at least 12 months of ADT use had the greatest absolute increased risk of dementia (hazard ratio, 2.36; 95% CI, 1.64-3.38; P < .001). Kaplan-Meier analysis demonstrated that ADT users 70 years or older had the lowest cumulative probability of remaining dementia free (log-rank P < .001).Conclusions and RelevanceAndrogen deprivation therapy in the treatment of prostate cancer may be associated with an increased risk of dementia. This finding should be further evaluated in prospective studies.

Simultaneous Liver-Kidney Transplantation in Liver Transplant Candidates With Renal Dysfunction: Importance of Creatinine Levels, Dialysis, and Organ Quality in Survival

IntroductionThe survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK survival has not been well described in the literature.MethodsThe Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N = 2700) or SLK (N = 1361) with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into 4 groups based on serum creatinine (<2 mg/dl versus ≥2 mg/dl) and dialysis status at listing and transplant. The patients with end-stage renal disease and requiring acute dialysis more than 3 months before transplantation were excluded. A propensity score matching was performed in each stratified group to factor out imbalances between the SLK and LTA regarding covariate distribution and to reduce measured confounding. Donor quality was assessed with liver donor risk index. The primary outcome of interest was posttransplant mortality.ResultsIn multivariable propensity score-matched Cox proportional hazard models, SLK led to decrease in posttransplant mortality compared with LTA across all 4 groups, but only reached statistical significance (hazard ratio 0.77; 95% confidence interval, 0.62–0.96) in the recipients not exposed to dialysis and serum creatinine ≥ 2 mg/dl at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, P = 0.005). The decrease in mortality was observed among SLK recipients with better quality donors (liver donor risk index < 1.5).DiscussionExposure to pretransplantation dialysis and donor quality affected overall survival among SLK recipients.

Association between acetylcholinesterase inhibitors and risk of stroke in patients with dementia.

Patients with dementia are at increased risk of stroke. Acetylcholinesterase inhibitors (AChEIs) have endothelial function protection effects and anti-inflammatory properties. We investigated the ischemic stroke risk in AChEIs use in dementia patients without stroke history. Using Taiwan National Health Insurance Database from 1999 to 2008, 37,352 dementia patients over 50 years old without stroke history were eligible. The results were analyzed by propensity score–matched Cox proportional hazard models with competing risk adjustment. AChEIs users had lower incidence of ischemic stroke (160.3/10,000 person-years), compared to the propensity score–matched reference (240.8/10,000 person-years). The adjusted hazard ratio for ischemic stroke based on propensity score–matched Cox proportional hazard model was 0.508 (95% confidence interval, 0.434–0.594; P < 0.001). There was no significant difference in all-cause mortality between AChEIs users and nonusers. In conclusion, among dementia patients without previous ischemic stroke history, AChEIs treatment was associated with a decreased risk of ischemic stroke but not greater survival.

Abstract 16261: Risk of Stroke or Systemic Embolism After Transseptal Ablation in Patients With Implanted Cardiac Devices

Introduction: Mobile thrombi are commonly observed on endovascular leads at the time of catheter ablation. Transseptal puncture poses a risk of paradoxical embolism. We sought to examine the risk of stroke or systemic embolism after transseptal ablation in patients with and without cardiac implantable electronic devices (CIEDs). Methods: Using a large, national administrative claims database we identified 31,720 patients who underwent a catheter ablation requiring transseptal puncture between 1/1/2004 and 9/30/2014. We created two propensity-matched cohorts, matching on age, gender, race, household income, region, Charlson index, CHADS-Vasc score, and year and indication for ablation (5,533 patients with CIEDs and 11,300 patients without devices). Incidence rates (events/100 patient-years) and propensity score-matched cox proportional hazards models (with 95% confidence intervals) were used to estimate risk of stroke, transient ischemic attack, or systemic embolism for patients with or without CIEDs. We also examined the impact of presence of a CIED and oral anticoagulation (OAC) use on risk of stroke or systemic embolism within the matched cohort. Average follow up was 2.1 years. Results: The event rate was 1.5 per 100 person years in patients without device, and 1.9 per 100 person years in patients with device. Among patients not on OAC, presence of a cardiac device was associated with an increased risk of stroke or systemic embolism (HR 1.71 [1.24-2.35], P&lt;0.01) whereas there was no association among patients treated with OAC (0.98 [0.75_1.28], p=ns) (Figure). Conclusions: Cardiac devices are associated with an increased risk of stroke or systemic embolism after transseptal ablation, but this risk is attenuated with post ablation OAC use. Anticoagulation should be considered for all patients with CIEDs post transseptal ablation, regardless of the presence of another compelling indication for anticoagulation.

Moving to a Highly Walkable Neighborhood and Incidence of Hypertension: A Propensity-Score Matched Cohort Study.

Background:The impact of moving to a neighborhood more conducive to utilitarian walking on the risk of incident hypertension is uncertain.Objective:Our study aimed to examine the effect of moving to a highly walkable neighborhood on the risk of incident hypertension.Methods:A population-based propensity-score matched cohort study design was used based on the Ontario population from the Canadian Community Health Survey (2001–2010). Participants were adults ≥ 20 years of age who moved from a low-walkability neighborhood (defined as any neighborhood with a Walk Score < 90) to either a high- (Walk Score ≥ 90) or another low-walkability neighborhood. The incidence of hypertension was assessed by linking the cohort to administrative health databases using a validated algorithm. Propensity-score matched Cox proportional hazard models were used. Annual health examination was used as a control event.Results:Among the 1,057 propensity-score matched pairs there was a significantly lower risk of incident hypertension in the low to high vs. the low to low-walkability groups [hazard ratio = 0.46; 95% CI, 0.26, 0.81, p < 0.01]. The crude hypertension incidence rates were 18.0 per 1,000 person-years (95% CI: 11.6, 24.8) among the low- to low-walkability movers compared with 8.6 per 1,000 person-years (95% CI: 5.3, 12.7) among the low- to high-walkability movers (p < 0.001). There were no significant differences in the hazard of annual health examination between the two mover groups.Conclusions:Moving to a highly walkable neighborhood was associated with a significantly lower risk of incident hypertension. Future research should assess whether specific attributes of walkable neighborhoods (e.g., amenities, density, land-use mix) may be driving this relationship.Citation:Chiu M, Rezai MR, Maclagan LC, Austin PC, Shah BR, Redelmeier DA, Tu JV. 2016. Moving to a highly walkable neighborhood and incidence of hypertension: a propensity-score matched cohort study. Environ Health Perspect 124:754–760; http://dx.doi.org/10.1289/ehp.1510425

Association between Withholding Angiotensin Receptor Blockers in the Early Postoperative Period and 30-day Mortality: A Cohort Study of the Veterans Affairs Healthcare System.

Despite widespread use, there is limited information to guide perioperative management of angiotensin receptor blockers (ARBs). In this retrospective cohort study, the authors evaluated the patterns of postoperative ARB use in veterans regularly prescribed ARBs admitted for noncardiac surgery at the Veterans Affairs Healthcare system between 1999 and 2011. Multivariable and propensity score-matched Cox proportional hazards models were used to determine the independent effect of failure to resume ARB by postoperative day 2 on the primary outcome of all-cause 30-day mortality. Out of 1,167,482 surgical admissions, 30,173 inpatient surgical admissions met inclusion criteria. Approximately 10,205 patients (33.8%) in the cohort did not resume ARB by day 2. Those that resumed ARB had a 30-day mortality rate of 1.3% (260 of 19,968), whereas 3.2% (323 of 10,205) died in the group that withheld ARB. The unadjusted hazard ratio (HR) for 30-day mortality was 2.45 (95% CI, 2.08 to 2.89; P < 0.001) for those that withheld ARB compared with those that resumed, whereas the multivariable adjusted HR was 1.74 (95% CI, 1.47 to 2.06; P < 0.001). When restricted to a propensity score-matched subset of 19,490, the HR was similar (1.47; 95% CI, 1.22 to 1.78; P < 0.001). Withholding ARB in younger patients increased mortality risk (HR = 2.52; 95% CI, 1.69 to 3.76; P < 0.001 for age <60 yr) compared with older patients (HR = 1.42; 95% CI, 1.09 to 1.85; P = 0.01 for age >75 yr). Postoperative delay in resuming ARB is common, particularly in patients who are frail after surgery. Withholding ARB is strongly associated with increased 30-day mortality, especially in younger patients, although residual confounding may be present.