Testosterone Therapy in Relation to Prostate Cancer in a U.S. Commercial Insurance Claims Database.

BACKGROUND: We conducted a study to assess whether testosterone therapy (TT) alters prostate cancer risk using a large U.S. commercial insurance research database. METHODS: From the HealthCore Integrated Research Database (HIRD), we selected men ages 30 years or greater who were new users of TT during 2007 to 2015. We selected two comparison groups: (i) unexposed (matched 10:1) and (ii) new users of phosphodiesterase type 5 inhibitor (PDE5i). Incident prostate cancer was defined as diagnosis of prostate cancer within 4 weeks following prostate biopsy. Propensity scores and inverse probability of treatment weights were used in Poisson regression models to estimate adjusted incidence rates, incidence rate ratios (IRR), and 95% confidence intervals (CI). Subgroup analyses included stratification by prostate cancer screening, hypogonadism, and follow-up time. RESULTS: The adjusted prostate cancer IRR was 0.77 (95% CI, 0.68-0.86) when comparing TT with the unexposed group and 0.85 (95% CI, 0.79-0.91) in comparison with the PDE5i group. Inverse associations between TT and prostate cancer were observed in a majority of subgroup analyses, although in both comparisons estimates generally attenuated with increasing time following initial exposure. Among TT users, duration of exposure was not associated with prostate cancer. CONCLUSIONS: Men who received TT did not have a higher rate of prostate cancer compared with the unexposed or PDE5i comparison groups. The inverse association between TT and prostate cancer could be the result of residual confounding, contraindication bias, or undefined biological effect. IMPACT: This study suggests that limited TT exposure does not increase risk of prostate cancer in the short term.

Benchmarking Danish hospitals on mortality and readmission rates after cardiovascular admission.

OBJECTIVE: The aim of this study was to examine hospital performance measures that account more comprehensively for unique mixes of patients' characteristics. DESIGN: Nationwide cohort registry-based study within a population-based health care system. PARTICIPANTS: In this study, 331,513 patients discharged with a primary cardiovascular diagnosis from 1 of 26 Danish hospitals during 2011-2015 were included. Data covering all Danish hospitals were drawn from the Danish National Patient Registry and the Danish National Health Service Prescription Database. MAIN OUTCOME MEASURES: Thirty-day post-admission mortality rates, 30-day post-discharge readmission rates, and the associated numbers needed to harm were measured. METHODS: For each index hospital, we used a non-parametric logistic regression model to compute propensity scores. Propensity score weighted patients treated at other hospitals collectively resembled patients treated at the index hospital in terms of age, sex, primary discharge diagnosis, diagnosis history, medications, previous cardiac procedures, and comorbidities. Outcomes for the weighted patients treated at other hospitals formed benchmarks for the index hospital. Doubly robust regression formally tested whether the outcomes of patients at the index hospital differed from the outcomes of the patients used to form the benchmarks. For each index hospital, we computed the false discovery rate, ie, the probability of being incorrect if we claimed the hospital differed from its benchmark. RESULTS: Five hospitals exceeded their benchmark for 30-day mortality rates, with the number needed to harm ranging between 55 and 137. Seven hospitals exceeded their benchmark for readmission, with the number needed to harm ranging from 22 to 71. Our benchmarking approach flagged fewer hospitals as outliers compared with conventional regression methods. CONCLUSION: Conventional methods flag more hospitals as outliers than our benchmarking approach. Our benchmarking approach accounts more thoroughly for differences in hospitals' patient case mix, reducing the risk of false-positive selection of suspected outliers. A more comprehensive system of hospital performance measurement could be based on this approach.

Development and Validation of an Algorithm for Identifying Patients with Hemophilia A in an Administrative Claims Database.

BACKGROUND: The accuracy with which hemophilia A can be identified in claims databases is unknown. OBJECTIVE: Develop and validate an algorithm using predictive modeling supported by machine learning to identify patients with hemophilia A in an administrative claims database. METHODS: We first created a screening algorithm using medical and pharmacy claims to identify potential hemophilia A patients in the US HealthCore Integrated Research Database between January 1, 2006 and April 30, 2015. Medical records for a random sample of patients were reviewed to confirm case status. In this validation sample, we used lasso logistic regression with cross-validation to select covariates in claims data and develop a predictive model to estimate the probability of being a confirmed hemophilia A case. RESULTS: The screening algorithm identified 2,252 patients and we reviewed medical records for 400 of these patients. The screening algorithm had a positive predictive value (PPV) of 65%. The predictive model identified 18 predictors of being a hemophilia A case or noncase. The strongest predictors of case status included male sex, factor VIII therapy, office visits for hemophilia A, and hospitalizations for hemophilia A. The strongest predictors of noncase status included hospitalizations for reasons other than hemophilia A and factor VIIa therapy. A probability threshold of ≥0.6 resulted in a PPV of 94.7% (95% CI: 92.0-97.5) and sensitivity of 94.4% (95% CI: 91.5-97.2). CONCLUSIONS: We developed and validated an algorithm to identify hemophilia A cases in an administrative claims database with high sensitivity and high PPV.

Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men.

BACKGROUND: An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly. METHODS: We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation. RESULTS: In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥ 75 years (p trend = 0.03), while no trend was seen for PDE5I (p trend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11). DISCUSSION: In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.

Second-generation antihistamines exhibit a protective effect on drivers in traffic-a preliminary population-based case-control study.

INTRODUCTION: Although there have been experimental studies concerning driving and drugs, studies on the risk of antihistamines are not numerous. This is the first population-based epidemiological study concerning the association of sedating/nonsedating antihistamines and fatal traffic accidents. METHODS: Car drivers (n = 428) who died in accidents before reaching the hospital and controls (n = 688) matched for accident area and driving season were studied for antihistamines in blood. At the time of the fatal road traffic accident, 6 drivers had a detectable amount of sedating antihistamines in blood, and the corresponding number for controls was 4; nonsedating antihistamines in blood were detected in 12 accident cases and 28 controls. The fatal accidents occurred between 1998 and 2002 and the information on the controls was collected between 2000 and 2002 in Finland. RESULTS: Regarding fatal traffic accident causality, the nonsedating antihistamines proved to have a protective effect after adjusting for age and gender (relative risk = 0.40, 95% confidence interval [CI], 0.20 to 0.82; P =.01). The risk of fatal traffic accident of those driving under the influence of sedating antihistamines was 1.61 (0.38 to 6.77, P =.51) times the risk of those without medication. DISCUSSION: This preliminary study supports the protective effect of second-generation antihistamines with respect to fatal traffic accidents. Due to the small sample size the results are not conclusive.

Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults.

OBJECTIVES: To determine whether zolpidem is a safer alternative to benzodiazepines. DESIGN: Retrospective cohort study. SETTING: Community based. PARTICIPANTS: Health maintenance organization members with an initial prescription for zolpidem (n = 43,343), alprazolam (n = 103,790), lorazepam (n = 150,858), or diazepam (n = 93,618). MEASUREMENTS: Zolpidem and benzodiazepine prescriptions were identified from pharmacy databases. Rates of nonvertebral fractures and hip fractures requiring hospitalization were compared before and after an initial prescription for each treatment, adjusting for confounders using doubly robust estimation. RESULTS: In patients aged 65 and older, the rates of nonvertebral fractures and dislocations were similar in the pre- treatment intervals. The rate ratios (RRs) for the 90-day posttreatment interval relative to the pretreatment interval were 2.55 (95% confidence interval (CI) = 1.78-3.65; P < .001) for zolpidem, 1.14 (95% CI = 0.80-1.64; P = .42) for alprazolam, 1.53 (95% CI = 1.23-1.91; P < .001) for lorazepam, and 1.97 (95% CI = 1.22-3.18; P = .01) for diazepam. The ratio of RRs (RRR)-the RR in the posttreatment period adjusted for the corresponding RR in the pretreatment period-were 2.23 (95% CI = 1.36-3.66; P = .006) for zolpidem relative to alprazolam, 1.68 (95% CI = 1.12-2.53; P = .02) for zolpidem relative to lorazepam, and 1.29 (95% CI = 0.72-2.30; P = .32) for zolpidem relative to diazepam. The RRs decreased with time from the initial prescription (trend P < .001), as would be expected if the association is causal. CONCLUSION: In older adults, the risk of injury with zolpidem exceeded that with alprazolam and lorazepam and was similar to that with diazepam. If the associations are causal, then the high incidence of these fractures implies that these treatment induce a substantial number of fractures and consequential costs. Further study of the association is imperative.

A cohort study of systemic and local complications of toe prostheses.

We investigated the role of toe implants in systemic disease and evaluated local complications after foot surgery. Information was obtained from the medical records of Kaiser Permanente (northern California) patients who had undergone toe surgery between 1979 and 1988. Computerized hospitalization records were used to identify patients with toe implants (N=814) and matched controls with foot surgery not involving implants (N=837). Brain cancer and alopecia areata occurred more among implant patients, whereas dysphagia occurred more among nonimplant patients. A larger proportion of implant patients were diagnosed with pain and swelling, tendonitis, and osteomyelitis or periostitis. Nonimplant patients were more often diagnosed with derangement of foot or ankle and delayed postoperative healing. We did not find a general association between implants and connective tissue diseases.

Increased risk of serious injury following an initial prescription for diphenhydramine.

BACKGROUND: Diphenhydramine may be associated with excess risk of injury relative to nonsedating H1-receptor antagonists. OBJECTIVE: This study sought to compare the risk of injury in patients exposed to diphenhydramine with the risk of injury in patients exposed to loratadine. METHODS: A retrospective cohort study of injury was carried out in 12,106 patients whose initial antihistamine prescription was for diphenhydramine and in 24,968 patients whose initial antihistamine prescription was for loratadine. Data were taken from a health care claims database that included employees, dependents, and retirees who filed claims from January 1991 through December 1998. Rates of six serious injuries in the diphenhydramine cohort after and before the first prescription were compared with rates in the loratadine cohort after and before the first prescription. RESULTS: In the 30 days after the first antihistamine prescription, the rate of all injuries was 308 per 1,000 person-years in the diphenhydramine cohort versus 137 per 1,000 person-years in the loratadine cohort. The rate ratio estimate adjusted for age and gender using Poisson regression was 2.27 (95% confidence limits [CL] 1.93, 2.66). In the corresponding 30 days of the preceding year, the injury rates in the diphenhydramine and loratadine cohorts were 128 and 125 per 1,000 person-years, and the adjusted rate ratio was 1.02 (CL 0.83, 1.26). Thus, the cohorts appeared to have similar preprescription injury rates. The differences between the cohorts declined with time from prescription: For all injuries, the estimated percentage decline in the rate ratio was 4.1% per day (CL 3.3, 4.9), and the estimated time from the initial prescription until the diphenhydramine cohort returned to baseline risk was 32.3 days (CL 26.9, 37.6). CONCLUSIONS: If these associations are causal, the percentage of the injuries attributable to diphenhydramine was 55% (CL 41, 65), implying a substantial number of excess injuries and costs incurred as the result of diphenhydramine use. The high use rates of this drug and the high incidence of injury suggest that further study of the association between injury and type of antihistamine is needed.