Elizabeth Delzell

The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine.

The goal of our study was to estimate the prevalence of osteoporosis and low bone mass based on bone mineral density (BMD) at the femoral neck and the lumbar spine in adults 50 years and older in the United States (US). We applied prevalence estimates of osteoporosis or low bone mass at the femoral neck or lumbar spine (adjusted by age, sex, and race/ethnicity to the 2010 Census) for the noninstitutionalized population aged 50 years and older from the National Health and Nutrition Examination Survey 2005–2010 to 2010 US Census population counts to determine the total number of older US residents with osteoporosis and low bone mass. There were more than 99 million adults aged 50 years and older in the US in 2010. Based on an overall 10.3% prevalence of osteoporosis, we estimated that in 2010, 10.2 million older adults had osteoporosis. The overall low bone mass prevalence was 43.9%, from which we estimated that 43.4 million older adults had low bone mass. We estimated that 7.7 million non‐Hispanic white, 0.5 million non‐Hispanic black, and 0.6 million Mexican American adults had osteoporosis, and another 33.8, 2.9, and 2.0 million had low bone mass, respectively. When combined, osteoporosis and low bone mass at the femoral neck or lumbar spine affected an estimated 53.6 million older US adults in 2010. Although most of the individuals with osteoporosis or low bone mass were non‐Hispanic white women, a substantial number of men and women from other racial/ethnic groups also had osteoporotic BMD or low bone mass.

Association Between the Initiation of Anti–Tumor Necrosis Factor Therapy and the Risk of Herpes Zoster

IMPORTANCE Herpes zoster reactivation disproportionately affects patients with rheumatoid arthritis (RA). It is unclear whether anti-tumor necrosis factor (anti-TNF) therapy elevates herpes zoster risk. OBJECTIVES To ascertain whether initiation of anti-TNF therapy compared with nonbiologic comparators is associated with increased herpes zoster risk. DESIGN, SETTING, AND PATIENTS We identified new users of anti-TNF therapy among cohorts of patients with RA, inflammatory bowel disease, and psoriasis, psoriatic arthritis, or ankylosing spondylitis from 1998 through 2007 within a large US multi-institutional collaboration combining data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and national Medicaid/Medicare programs. We compared herpes zoster incidence between new anti-TNF users (n=33,324) and patients initiating nonbiologic disease-modifying antirheumatic drugs (DMARDs) (n=25,742) within each inflammatory disease cohort (last participant follow-up December 31, 2007). Within these cohorts, we used Cox regression models to compare propensity score-adjusted herpes zoster incidence between new anti-TNF and nonbiologic DMARD users while controlling for baseline corticosteroid use. MAIN OUTCOME MEASURES Incidence of herpes zoster cases occurring after initiation of new anti-TNF or nonbiologic DMARD therapy. RESULTS Among 33,324 new users of anti-TNF therapy, we identified 310 herpes zoster cases. Crude incidence rates among anti-TNF users were 12.1 per 1000 patient-years (95% CI, 10.7-13.6) for RA, 11.3 per 1000 patient-years (95% CI, 7.7-16.7) for inflammatory bowel disease, and 4.4 per 1000 patient-years (95% CI, 2.8-7.0) for psoriasis, psoriatic arthritis, or ankylosing spondylitis. Baseline use of corticosteroids of 10 mg/d or greater among all disease indications was associated with elevated risk (adjusted hazard ratio [HR], 2.13 [95% CI, 1.64-2.75]) compared with no baseline use. For patients with RA, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators (adjusted HR, 1.00 [95% CI, 0.77-1.29]) and comparable between all 3 anti-TNF therapies studied. Across all disease indications, the adjusted HR was 1.09 (95% CI, 0.88-1.36). CONCLUSION AND RELEVANCE Among patients with RA and other inflammatory diseases, those who initiated anti-TNF therapies were not at higher risk of herpes zoster compared with patients who initiated nonbiologic treatment regimens.

Cancer Incidence Among Triazine Herbicide Manufacturing Workers

This study evaluated cancer incidence and prostate specific antigen (PSA) testing among workers at a plant in Louisiana (LA) that made atrazine and other triazine herbicides. The study covered the time period 1985 through 1997 and included 2045 subjects, of whom 757 worked for the company that owned the plant and 1288 were contract employees. Linkage with a population-based cancer registry and review of death certificates and plant medical records identified cancer cases. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) compared subjects’ cancer incidence rates with those of a regional general population. Plant medical records provided data on the proportion receiving PSA tests among male company employees. Subjects had 46 observed and 40 expected cases of all cancers combined (SIR = 114, CI = 83–152) and had 11/6.3 prostate cancers (SIR = 175, CI = 87–312). The prostate cancer excess was greater in actively working company employees (5/1.3, SIR = 394, CI = 128–920) than in contract employees or inactive company employees (6/5.0, SIR = 119, CI = 44–260) and was limited to men under 60 years of age. Of the 11 prostate cancer cases, nine were diagnosed at an early clinical stage. From 1993 to 1999, the proportion of male company employees who had at least one PSA test was 86% for those who reached 40 years of age while actively working and was 98% for those who reached 45 years of age. The observed prostate cancer increase may have been due to the frequent PSA testing of actively working company employees. There is no epidemiologic or other information that clearly supports a causal relation between atrazine and prostate cancer.

Improving the prediction of medication compliance: the example of bisphosphonates for osteoporosis.

Introduction:Administrative claims data have a limited ability to identify persons with high compliance to oral bisphosphonates. We tested whether adding information on compliance with other drugs used to treat chronic, asymptomatic conditions would improve the predictive ability of administrative data to identify adherent individuals. Methods:Using data from a large, US healthcare organization, we identified new bisphosphonate users and their 1-year compliance to oral bisphosphonates, quantified by the Medication Possession Ratio (MPR). Multivariable logistic regression models evaluated the relationship between high bisphosphonate compliance (MPR ≥80%) and patient demographics, comorbidities, and health services utilization. To these logistic regression models, we evaluated the incremental change in the area under the receiver operator curve (AUC) after adding information regarding compliance with other drug classes. These included antihyperlipidemics (statins), antihypertensives, antidepressants, oral diabetes agents, and glaucoma medications. Results from the logistic regression models were evaluated in parallel using recursive partitioning trees with 10-fold cross-validation. Results:Among 101,038 new bisphosphonate users, administrative data identified numerous nonmedication factors (eg, age, gender, use of preventive services) significantly associated with high bisphosphonate compliance at 1 year. However, all these factors in aggregate had low discriminant ability to identify persons highly adherent with bisphosphonates (AUC = 0.62). For persons who were new users of ≥1 of the other asymptomatic condition drugs, MPR data on the other drugs substantially improved the prediction of high bisphosphonate compliance. The impact on prediction was largest for concomitant statin users (AUC = 0.70). Conclusions:Information on compliance with drugs used to treat chronic asymptomatic conditions improves the prediction of compliance with oral bisphosphonates. This information may help identify persons who should receive targeted interventions to promote compliance to osteoporosis medications.

An updated study of mortality among workers at a petroleum manufacturing plant.

This study evaluated mortality among 9796 white male workers at a petroleum-manufacturing plant. The main purpose was to examine recent patterns in leukemia mortality, for which an increase had been reported in an earlier investigation. Compared to U.S. white men, the cohort had an excess of leukemia in 1940-1979 (38 observed/23 expected; standardized mortality ratio= 168; 95% confidence interval = 119—230). In the 1980s, there was a deficit of leukemia (8 observed/14 expected; standardized mortality ratio = 55; 95% confidence interval = 24—108). However, this was balanced by an excess of myelofibrosis and myelodysplasia (4 observed, <1 expected). These results indicate that any occupational leukemogenic exposures at the plant have been reduced to a point at which they are insufficient to cause leukemia. Hourly workers also had an excess of deaths from mesothelioma in the 1980s (8 observed, about 2.5 expected), possibly because of exposure to asbestos in the past.

A Review of Epidemiologic Studies of Nonnarcotic Analgesics and Chronic Renal Disease

&NA; Abbreviations used in this article: AN, analgesic nephropathy; CI, confidence interval; CRD, chronic renal disease; ESRD, end‐stage renal disease; NAPAP, N‐acetyl‐p‐aminophenol; NSAIDs, nonsteroidal antiinflammatory drugs; RPN, renal papillary necrosis; RR, risk ratio.

Mortality among semiconductor and storage device-manufacturing workers.

Problem: We evaluated mortality during 1965 to 1999 among 126,836 workers at two semiconductor facilities and one storage device facility. Method: We compared employees’ cause-specific mortality rates with general population rates and examined mortality patterns by facility, duration of employment, time since first employment, and work activity. Results: Employees had lower-than-expected mortality overall (6579 observed deaths, standardized mortality ratio [SMR] = 65; 95% confidence interval [CI] = 64–67), for all cancers combined (2159 observed, SMR = 78, 95% CI = 75–81) and for other major diseases. Central nervous system cancer was associated with process equipment maintenance at one of the semiconductor facilities (10 observed, SMR = 247, 95% CI = 118–454). Prostate cancer was associated with facilities/laboratories at the storage device facility (18 observed, SMR = 198, (5% CI = 117–313). Conclusions: Further evaluation of workplace exposures or independent investigations of similar occupational groups may clarify the interpretation of associations observed in this study

Brain tumors among electronics industry workers.

We evaluated the relation between work experience in the United States operations of an electronics company and brain tumor mortality, focusing on video display terminal (VDT) development jobs. Subjects were 149 brain tumor cases and 591 matched controls selected from a company registry of all employees dying between 1975 and 1989. Company databases and interviews with company personnel constituted the basis for work histories, including information on whether subjects had held VDT development jobs. Subjects who worked at plants with hardware or VDT development operations had slightly but imprecisely elevated odds ratios (OR). The study found no meaningful association between VDT development work and brain tumor mortality. Other results included an elevated OR for 10 or more years of employment in engineering/technical jobs [OR = 1.7; 95% confidence interval (CI) = 1.0–3.0] or in programming jobs (OR = 2.8; 95% CI = 1.1–7.0). The OR for glioma for all subjects who had accrued 5 years of programming work 10 years before the cases death was 3.9 (95% CI = 1.2–12.4). These associations were limited in large part to one of four division groups. Also, only male programmers experienced an elevated OR. These patterns indicate that the associations may be due to chance, although unidentified causal exposures present in a subset of engineering/technical and programming jobs cannot be ruled out.

Death, Debility, and Destitution Following Hip Fracture

BACKGROUND We examined the effects of hip fracture on mortality, entry into long-term institutional care, and new evidence of poverty. We estimate of the proportion of hip fracture patients who require not just short-term rehabilitation but who become dependent on long-term institutional care, and the risk of becoming newly dependent on Medicaid or eligible for low-income subsidies following hip fracture. METHODS We used data from 2005 through 2010 for a random 5% sample of Medicare beneficiaries (N = 3.1 million) to conduct a retrospective matched cohort study. We used high-dimensional propensity score matching to compare outcomes for patients who experienced a hip fracture with subjects who did not, but had similar propensity for suffering a hip fracture. We then compared the 1-year risk of death, debility, and destitution between groups. RESULTS We matched 43,210 hip fracture patients to comparators without a hip fracture. Hip fractures were associated with more than a twofold increase in likelihood of mortality (incidence proportion ratio [IPR] of 2.27, 95% CI, 2.20-2.34), a fourfold increase in likelihood of requiring long-term nursing facility care (IPR, 3.96; 95% CI, 3.77-4.16), and a twofold increase in the probability of entering into low-income status (IPR, 2.14; 95% CI 1.99-2.31) within 1 year following hip fracture compared with subjects without a hip fracture. CONCLUSIONS Hip fracture in elderly patients resulted in increased death, debility, and destitution. Initiatives that lead to improved treatment of osteoporosis could result in a decrease in incidence of fractures, subsequent death, debility, and destitution for older adults.

Adaptation of Bayesian data mining algorithms to longitudinal claims data: coxib safety as an example.

Introduction:Bayesian data mining methods have been used to evaluate drug safety signals from adverse event reporting systems and allow for evaluation of multiple endpoints that are not prespecified. Their adaptation for use with longitudinal data such as administrative claims has not been previously evaluated or validated. Methods:In this pilot study, we evaluated the feasibility of adapting data mining methods using the empirical Bayes Multi-item Gamma Poisson Shrinkage (MGPS) algorithm to longitudinal administrative claims data. The Medicare Current Beneficiary Survey was used to identify a cohort of Medicare enrollees who were exposed to cyclooxygenase selective (coxib) or nonselective nonsteroidal anti-inflammatory drugs (NS-NSAIDs) from 1999 to 2003. Empirical Bayes MGPS algorithm was used to simultaneously evaluate 259 outcomes associated with current use of coxibs versus NS-NSAIDs while adjusting for key covariates and multiple comparisons. For comparison, a parallel analysis used traditional epidemiologic methods to evaluate the relationship between coxib versus NS-NSAID use and acute myocardial infarction, with the goal of establishing the concurrent validity of the data mining approach. Results:Among 9431 Medicare beneficiaries using NSAIDs and considering all 259 possible outcomes, empirical Bayes MGPS identified an association between current celecoxib use and acute myocardial infarction (Empirical Bayes Geometric Mean ratio 1.91) but not other outcomes. Rofecoxib use was associated with acute cerebrovascular events (Empirical Bayes Geometric Mean ratio 1.85) and several other diagnoses that likely represented indications for the drug. Results from the analyses using traditional epidemiologic methods were similar and indicated that the data mining results were valid. Discussion:Bayesian data mining methods seem useful to evaluate drug safety using administrative data. Further work will be needed to extend these findings to different types of drug exposures and to other claims databases.