OBJECTIVE:The comparative risk of infection associated with non-anti-tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non-anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA). METHODS:Using 1998-2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders. RESULTS:Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1-6.4) for rituximab, 2.8 (95% CI 1.7-4.7) for abatacept, and 3.0 (95% CI 2.5-3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9-2.2), abatacept (HR 1.1, 95% CI 0.6-2.1), or rituximab (HR 1.4, 0.8-2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3-4.0). Infection risk was greater for those taking prednisone >7.5 mg/day (HR 1.8, 95% CI 1.3-2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4-3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3-7.2) compared to the lowest quartile. CONCLUSION:In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.

We examined the use of pharmacologic agents for the primary prevention of osteoporosis among older women with osteopenia. We found that these individuals were not managed in concordance with the National Osteoporosis Foundation (NOF) guidelines and that self-perceived osteoporosis risk and lower bone density were strongly associated with receipt of treatment.

Background Risks of hospitalized infections associated with newer biologic agents have not been well characterized in relation to risks with anti-TNF therapy, especially in rheumatoid arthritis (RA) patients with high comorbidity burdens. Objectives To compare the risk of hospitalized infections among RA patients switching from anti-TNF therapy to rituximab (RTX), abatacept (ABA) or another anti-TNF. Methods Using data from 2002-10 from the U.S. Veteran’s Health Administration, we identified a cohort of 38453 RA patients. Eligible patients started RTX, ABA, or anti-TNF therapy after prior exposure to another anti-TNF agent. To minimize confounding from channeling of cancer patients to certain biologics, patients with a history of cancer were excluded to form 2 cohorts: Exclusion for any type of prior cancer using all available data (3257 episodes, 2559 patients) or exclusion only for hematologic cancer in the prior 12 months (3848 episodes, 3018 patients). Baseline characteristics defined in 1 year prior to treatment initiation. Exposure was as-treated based upon days supply (injections) or usual dosing intervals (infusions), with 12 months assumed for RTX exposure. Current exposure was extended by 90 days for all biologics. The outcome was hospitalization with primary diagnosis code for bacterial infection. The hazard ratio (HR, 95% CI) for infection for RTX and ABA vs. anti-TNFs was calculated, adjusting for multiple potential confounders. Results 523 RTX, 366 ABA and 2959 anti-TNF switcher episodes were identified in RA patients without hematologic cancers; 15% of treatment episodes were further excluded with the more restrictive cancer exclusion to form a 2nd cohort. This cohort’s mean overall age was 60.8±10.7 years, 87% male, 25% diabetes, 15% COPD, 3% heart failure, and 66% used glucocorticoids. 2/3rd of the anti-TNF exposure was adalimumab. The most common types of hospitalized infections were pneumonia (36%), skin/soft tissue infections (26%), gastroenteritis (7%) and urinary tract infections (6%). In the less restrictive RA cohort, crude hospitalized infection rates/100person years were RTX: 15.9, ABA: 10.2 and anti-TNF: 12.7. In the less restrictive RA cohort, adjusted HRs for infection were comparable to or lower than for anti-TNF therapy: RTX: 0.85 (0.62-1.12) and ABA: 0.72 (0.50-1.10). In the more restrictive RA cohort, results were similar: adjusted HR for RTX: 0.76 (0.50-1.15) and ABA: 0.58 (0.36-0.93) compared to anti-TNF therapy. Multiple comorbidities and medications were associated with infections (diabetes HR=1.4, 95% CI 1.1-1.7; chronic lung disease HR=1.5, 1.1–1.9; prednisone >7.5mg/day HR=2.1, 1.6-2.7). Conclusions In older, predominantly male, US veterans with RA and high comorbidities, risks of hospitalized bacterial infections for patients treated with RTX or ABA were comparable to or lower than for patients switching to a different anti-TNF therapy (mostly ADA). Ongoing work is characterizing the comparative risks of opportunistic infections. Disclosure of Interest J. Curtis Consultant for: Roche/Genetech, UCB, Centocor CORRONA, Amgen, Pfizer, BMS, Crescendo, Abbott, S. Yang: None Declared, N. Patkar: None Declared, L. Chen: None Declared, J. Singh Grant/Research support from: Takeda, Savient, Consultant for: URL pharmaceuticals, Takeda, Ardea, Savient, Allergan, Novartis, G. Cannon: None Declared, T. Mikuls: None Declared, E. Delzell Grant/Research support from: Amgen, K. Saag Consultant for: Amgen; Lilly; Merck; Novartis; Savient; Ardea; Regeneron; URL, Abbott; DSMB – BioCryst; Roche; Lilly, M. Safford: None Declared, S. Duvall Grant/Research support from: Anolinx, LLC, Genentech, Roche, Amgen, Shire, K. Alexander Employee of: Genetech, P. Napalkov Employee of: Genetech, A. Kamauu Employee of: President- Anolinx LLC, J. Baddley Consultant for: Abbott, Merck

Medicare claims data were used to investigate associations between history of previous fractures, chronic conditions, and demographic characteristics and occurrence of fractures at six anatomic sites. The study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures.This study investigates the associations of a history of fracture, comorbid chronic conditions, and demographic characteristics with incident fractures among Medicare beneficiaries. The majority of fracture incidence studies have focused on the hip and on white females. This study examines a greater variety of fracture sites and more population subgroups than prior studies.We used Medicare claims data to examine the incidence of fracture at six anatomic sites in a random 5% sample of Medicare beneficiaries during the time period 2000 through 2005.For each type of incident fracture, women had a higher rate than men, and there was a positive association with age and an inverse association with income. Whites had a higher rate than nonwhites. Rates were lowest among African-Americans for all sites except ankle and tibia/fibula, which were lowest among Asian-Americans. Rates of hip and spine fracture were highest in the South, and fractures of other sites were highest in the Northeast. Fall-related conditions and depressive illnesses were associated with each type of incident fracture, conditions treated with glucocorticoids with hip and spine fractures and diabetes with ankle and humerus fractures. Histories of hip and spine fractures were associated positively with each site of incident fracture except ankle; histories of nonhip, nonspine fractures were associated with most types of incident fracture.This study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures.

Information on the impact of bone metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified men aged 65 years or older diagnosed with prostate cancer between July 1 1999 and December 31 2005 and followed to determine deaths through December 31 2006. We classified subjects as having bone metastasis and SREs as indicated by Medicare claims. Using Cox regression, we estimated mortality hazards ratios (HR) among men with bone metastasis with or without SRE, compared with men without bone metastasis. Among 126 978 men with prostate cancer (median follow-up, 3.3 years), 9746 (7.7%) had bone metastasis at prostate cancer diagnosis (1.7%) or during follow-up (5.9%). SREs occurred in 4296 (44%) men with bone metastasis. HRs for risk of death were 6.6 (95% CI=6.4–6.9) and 10.2 (95% CI=9.8–10.7), respectively, for men with bone metastasis but no SRE and for men with bone metastasis plus SRE, compared with men without bone metastasis. Bone metastasis was associated with mortality among prostate cancer patients. This association appeared to be stronger for bone metastasis plus SRE than for bone metastasis without SRE.

Objective. To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists.Methods. We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000-2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data >= 6 months prior to PML diagnosis.Results. Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy.Conclusion. PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.

OBJECTIVE Asbestos is an established human carcinogen and has been identified at 16 of 26 Jamaican hospitals surveyed. We sought to determine if hospital employees are exposed and if current asbestos exposure in Jamaican hospitals differed by job category. METHOD At two of the largest hospitals with more than 10 permanent maintenance workers and where over 67% of bulk samples analysed contained asbestos, three groups of employees selected by stratified random sampling participated in a personal air sampling study for asbestos. One hundred and thirty-two personal air samples and 32 area samples were collected and analysed for asbestos fibres utilizing phase contrast microscopy (PCM) and transmission electron microscopy (TEM). RESULTS Twenty-four (14.6%) air samples had fibre counts above the limit of detection (LOD) for the analytical method (PCM), ranging from 0.002 f/cc to 0.013 f/cc. The fibres met the dimensional characteristics of asbestos fibres. There was no difference in the median fibre concentration to which the groups of employees were exposed. Further testing of samples which had fibre counts above the LOD using TEM confirmed that the fibres were not asbestos. CONCLUSION Despite not finding asbestos fibres in the air samples, most of the asbestos containing building material (ACBM) found in the hospitals was friable and in a poor condition indicative of fibre release. We recommend an ongoing monitoring programme for airborne asbestos fibres in hospitals until an abatement programme can be undertaken by the regulatory agencies in the country.

The comparative effectiveness of alendronate and risedronate has received limited evaluation. Among 19,063 new users of bisphosphonates, risedronate users had a higher relative rate of hip fracture compared to alendronate users, but the difference in absolute fracture rate was small. We conclude that the agents have comparable efficacy.

Estimates of osteoporosis (OP) prevalence based on bone mineral density testing and fracture occurrence may be imprecise for small demographic groups. Medicare data are a useful supplemental source of information on OP.

Using national Medicare data from 1999–2006, we evaluated the relationship between travel distance and receipt of dual-energy X-ray absorptiometry (DXA). After adjusting for potentially confounding factors, travel distance was strongly associated with DXA testing. Rural residents were most strongly dependent on the availability of DXAs performed in physician offices.

Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy.

Aims: To evaluate cancer incidence among workers at two facilities in the USA that made semiconductors and electronic storage devices. Methods: 89 054 men and women employed by International Business Machines (IBM) were included in the study. We compared employees’ incidence rates with general population rates and examined incidence patterns by facility, duration of employment, time since first employment, manufacturing era, potential for exposure to workplace environments other than offices and work activity. Results: For employees at the semiconductor manufacturing facility, the standardised incidence ratio (SIR) for all cancers combined was 81 (1541 observed cases, 95% confidence interval (CI) 77 to 85) and for those at the storage device manufacturing facility the SIR was 87 (1319 observed cases, 95% CI 82 to 92). The subgroups of employees with ≥15 years since hiring and ≥5 years worked had 6–16% fewer total incidents than expected. SIRs were increased for several cancers in certain employee subgroups, but analyses of incidence patterns by potential exposure and by years spent and time since starting in specific work activities did not clearly indicate that the excesses were due to occupational exposure. Conclusions: This study did not provide strong or consistent evidence of causal associations with employment factors. Data on employees with long potential induction time and many years worked were limited. Further follow-up will allow a more informative analysis of cancer incidence that might be plausibly related to workplace exposures in the cohort.

The objectives were to estimate the recent burden of osteoporosis (OP) using Medicare claims data and to assess variation in OP prevalence by age, gender, race, and geographic region. The Medicare Chronic Condition Data Warehouse provided 1999–2004 claims data on an enhanced 5% probability sample of Medicare beneficiaries. The analysis included beneficiaries covered for 12 months in each year by Medicare part A and B and not enrolled in a health maintenance organization. We developed four case definitions for OP using increasingly rigorous criteria for assessing the patterns of claims for OP. We also developed two estimates of the burden of OP. The first was the proportion of beneficiaries that had at least one claim for OP in each year. The second was the prevalence of OP in 2004, calculated as the proportion of beneficiaries with at least one claim for OP during the entire study period of 1999 to 2004. Results using the most conservative case definition are presented. Sensitivity analyses based on variations in case definitions, insurance coverage requirements and other factors were conducted. From 1999 to 2004, the total number of eligible beneficiaries ranged from 1,712,614 to 1,855,200 persons, a substantial proportion of whom was 65–74 years (36.9%–38.3%), female (61.2%–63.0%), white (86.0%–86.9%) or black (8.9%–9.4%). Using the most rigorous OP definition, the annual proportion of beneficiaries with at least one OP claim ranged from 5.2% in 1999 to 6.6% in 2004. Overall OP prevalence was 14.9% in 2004. OP prevalence was 15.7 % among whites and 6.7% among African Americans; was higher in women (22.1%) compared to men (3.4%); and increased with age, from 5.4% among those under 65 to 22.6% among those 85+ years of age. Regional variation in prevalence was small. These results indicate sizeable differences in the burden of OP according to race, gender, and age. Results are discussed with respect to the varying case definitions and the methodological limitations of using claims data for epidemiologic studies.