Claire Canning

A Cohort Study of Thiazolidinediones and Fractures in Older Adults with Diabetes

CONTEXT Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. OBJECTIVE The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. DESIGN We conducted a cohort study. PARTICIPANTS Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. MAIN OUTCOME We measured the incidence of fracture within the cohort. RESULTS Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98-1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94-1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. CONCLUSIONS As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.

Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy

OBJECTIVES To evaluate the validity of patient report, pharmacy dispensing records, and pill counts as measures of antihypertensive adherence using electronic monitoring as the validation standard. METHODS The study was conducted among 286 members of Harvard Pilgrim Health Care, a managed care organization, who were at least 18 years of age, on monotherapy for hypertension, and had prescription drug coverage. Prescription refill adherence during the 12 months before enrollment was determined from their automated pharmacy dispensing records. Participants were interviewed about their medication adherence before and after a 3-month electronic monitoring period during which pill counts were also performed. Adherence to both recommended number and timing of doses was estimated from electronic monitoring data. Data analysis was based on statistical correlation and analysis of variance. RESULTS Electronic adherence monitoring revealed that the proportion of prescribed doses consumed was higher (0.92) than the proportion of doses taken on time (0.63). The correlation between adherence to quantity and timing of doses was 0.32. Concurrent pill counts and earlier refilling patterns were moderately correlated with electronic monitoring (pill count: r = .52 with quantity and r = .17 with timing; refill adherence r = .32 with quantity and r = .22 with timing). There was considerable misclassification of adherence reported by patients, although nonadherence was generally accurately reported. CONCLUSIONS Deviation from recommended timing of doses appears to be greater than from prescribed number of doses. Pharmacy dispensing records demonstrate predictive validity as measures of cumulative exposure and gaps in medication supply. Adherence levels determined from pill counts and pharmacy dispensing records correlate more closely with quantity than with timing of doses. Nonadherence reported by patients can serve as a qualitative indicator and predictor of reduced adherence.

Patterns of cardiovascular risk in rheumatoid arthritis

Background: Although it is known that rheumatoid arthritis is associated with an increased risk of cardiovascular disease (CVD), the pattern of this risk is not clear. This study investigated the relative risk of myocardial infarction, stroke and CVD mortality in adults with rheumatoid arthritis compared with adults without rheumatoid arthritis across age groups, sex and prior CVD event status. Methods: We conducted a cohort study among all residents aged ⩾18 years residing in British Columbia between 1999 and 2003. Residents who had visited the doctor at least thrice for rheumatoid arthritis (International Classification of Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and start of follow-up. The primary composite end point was a hospital admission for myocardial infarction, stroke or CVD mortality. Results: 25 385 adults who had at least three diagnoses for rheumatoid arthritis during the study period were identified. During the 5-year study period, 375 patients with rheumatoid arthritis had a hospital admission for myocardial infarction, 363 had a hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one of these outcomes. The rate ratio for a CVD event in patients with rheumatoid arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio decreased with age, from 3.3 in patients aged 18–39 years to 1.6 in those aged ⩾75 years. However, the rate difference was 1.2 per 1000 person-years in the youngest age group and increased to 19.7 per 1000 person-years in those aged ⩾75 years. Among patients with a prior CVD event, the rate ratios and rate differences were not increased in rheumatoid arthritis. Conclusions: This study confirms that rheumatoid arthritis is a risk factor for CVD events and shows that the rate ratio for CVD events among subjects with rheumatoid arthritis is highest in young adults and those without known prior CVD events. However, in absolute terms, the difference in event rates is highest in older adults.

Association Between Disease-Modifying Antirheumatic Drugs and Diabetes Risk in Patients With Rheumatoid Arthritis and Psoriasis

CONTEXT Rheumatoid arthritis (RA) and psoriasis have been linked with insulin resistance and diabetes mellitus (DM). Prior investigations suggest that systemic immunosuppressive drugs may improve insulin resistance and reduce the risk of DM. OBJECTIVE To compare the risk of newly recorded DM among participants diagnosed with RA or psoriasis based on use of a variety of disease-modifying antirheumatic drugs (DMARDs). DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study among 121,280 patients with a diagnosis of either RA or psoriasis on at least 2 visits. The analyses were conducted in the context of 2 large health insurance programs, 1 in Canada and 1 in the United States, using administrative data. The mean follow-up was 5.8 months and began with the first prescription for a DMARD after study eligibility was met. Drug regimens were categorized into 4 mutually exclusive groups: (1) tumor necrosis factor (TNF) inhibitors with or without other DMARDs; (2) methotrexate without TNF inhibitors or hydroxychloroquine; (3) hydroxychloroquine without TNF inhibitors or methotrexate; or (4) other nonbiologic DMARDs without TNF inhibitors, methotrexate, or hydroxychloroquine (reference exposure). MAIN OUTCOME MEASURE Newly recorded DM as evidenced by a new diagnosis of DM with use of a DM-specific medication. RESULTS The study cohort consisted of 13,905 participants with 22,493 treatment episodes starting 1 of the categories of DMARD regimens between January 1996 and June 2008. New diabetes cases and respective incidence rates per 1000 person-years were: other nonbiologic DMARDs (55 cases among 3993 treatment episodes; rate, 50.2; 95% confidence interval [CI], 47.3-53.2); TNF inhibitors (80 cases among 4623 treatment episodes; rate, 19.7; 95% CI, 19.1-20.3); methotrexate (82 cases among 8195 treatment episodes; rate, 23.8; 95% CI, 23.0-24.6); and hydroxychloroquine (50 cases among 5682 treatment episodes; rate, 22.2; 95% CI, 21.3-23.1). The multivariate adjusted hazard ratios for DM were 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, 0.77 (95% CI, 0.53-1.13) for methotrexate, and 0.54 (95% CI, 0.36-0.80) for hydroxychloroquine compared with other nonbiologic DMARDS. CONCLUSION Among patients with RA or psoriasis, the adjusted risk of DM was lower for individuals starting a TNF inhibitor or hydroxychloroquine compared with initiation of other nonbiologic DMARDs.

Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections

Background  There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD).

Risk of diabetes among patients with rheumatoid arthritis, psoriatic arthritis and psoriasis

Objective To examine the risk of diabetes mellitus (DM) among subjects with rheumatoid arthritis (RA), psoriatic arthritis or psoriasis (PsA/PsO), compared with non-rheumatic controls. Methods Study cohorts were assembled using linked healthcare utilisation data from British Columbia. All people with at least two diagnoses of RA or PsA/PsO were included and compared with a cohort of people without any known rheumatic disease. The outcome of interest was a diagnosis of new-onset DM, as defined by initiation of an antidiabetic drug. Incidence rates (IRs) per 1000 person-years and IR ratios were calculated and Cox regression models were constructed to determine the hazard ratio (HR) for diabetes by age, gender, systemic immunosuppressive drug and glucocorticoid use. Results The study cohort comprised 48 718 subjects with RA, 40 346 with PsA/PsO and 442 033 without any rheumatic disease. The IR for DM among subjects with RA was 8.6 per 1000 person-years (95% CI 8.5 to 8.7), PsA/PsO 8.2 (95% CI 8.1 to 8.3) and for non-rheumatic controls 5.8 (95% CI 5.8 to 5.8). The adjusted HR for RA compared with non-rheumatic controls was 1.5 (95% CI 1.4 to 1.5) and 1.4 (95% CI 1.3 to 1.5) for PsA/PsO. Conclusions RA and PsA/PsO appear to be associated with an increased risk of DM. The ability of potent antirheumatic treatments to reverse this trend warrants study.

Potential causes of higher mortality in elderly users of conventional and atypical antipsychotic medications.

OBJECTIVES: To investigate the potential mechanisms through which conventional antipsychotic medication (APM) might act, the specific causes of death in elderly patients newly started on conventional APM were compared with those of patients taking atypical APM.

Utilization and cost of immunotherapy for allergic asthma and rhinitis

BACKGROUND Allergic rhinitis and asthma are important sources of morbidity among adults and children. Although immunotherapy is sometimes used to treat these conditions, there is little information on its use, adherence, or cost in the general population. OBJECTIVE We sought to characterize the recipients of immunotherapy for allergic rhinitis and/or asthma with respect to their immunotherapy and utilization of health care services. METHODS A combination of automated and manually extracted data was used to identify HMO members with diagnoses of allergic rhinitis or asthma who were treated with immunotherapy. Costs associated with immunotherapy and related care were examined by linear regression. Proportional hazards and Kaplan-Meier plots were used to evaluate duration of therapy. RESULTS Of the 122,196 persons with a diagnosis of asthma or rhinitis, 2,667 were also treated with immunotherapy. Eligibility criteria were satisfied by 603 individuals who had 28,266 encounters for immunotherapy (median 48). Most patients (>80) were treated with multiple allergens; ragweed was the most common single allergen administered. Thirty-three percent of patients with sufficient observation time completed the intended course of 61 immunotherapy treatments. Females and younger patients had shorter durations of immunotherapy. The most common reason for discontinuation of therapy was patients decision (54%). Immunotherapy costs were related most strongly to costs for care of rhinitis and asthma. Prescription drugs accounted for more than 50% of the non-immunotherapy costs; hospitalizations accounted for less than 20%. CONCLUSIONS Approximately 2% of HMO members with an asthma or rhinitis diagnosis received immunotherapy. Although screened to optimize compliance, most patients did not complete immunotherapy. Costs of non-immunotherapy care were higher for individuals who completed immunotherapy which is consistent with more severe disease in this group.

A therapeutic substitution policy for proton pump inhibitors: Clinical and economic consequences

With the growing need to provide prescription drug benefits to older patients and to contain costs, it will be necessary to direct that coverage so as to make expenditures as efficient as possible. We evaluated the clinical and economic consequences of coverage restriction for 3 leading proton pump inhibitors (PPIs) in a large‐scale natural experiment.

Identification of hospitalizations for intentional self-harm when E-codes are incompletely recorded.

Suicidal behavior has gained attention as an adverse outcome of prescription drug use. Hospitalizations for intentional self‐harm, including suicide, can be identified in administrative claims databases using external cause of injury codes (E‐codes). However, rates of E‐code completeness in US government and commercial claims databases are low due to issues with hospital billing software.