Rates of non-vertebral osteoporotic fractures in rheumatoid arthritis and postfracture osteoporosis care in a period of evolving clinical practice guidelines.

In 2002, guidelines for the management of osteoporosis were published by Osteoporosis Canada and widely disseminated. We aimed to assess if those guidelines had any impact on clinical practice and ultimately on fracture rates in rheumatoid arthritis (RA). This was an observational study using the Quebec healthcare databases. To quantify the use of osteoporosis drugs, hormone replacement therapy (HRT), bone mineral density (BMD) testing, and fracture rates, quarterly age-standardized rates between 1998 and 2008 were calculated. A time series approach was used to predict fracture rates from 2003 onward, based on the earlier data. The provision of postfracture osteoporosis care, as defined by the initiation of osteoporosis drugs, HRT, or BMD testing, was examined; and logistic regressions identified factors associated with care. The study population in each quarter was mainly composed of older women. The use of osteoporosis drugs and BMD testing increased over the study period. The actual fracture rates from 2003 onward fell within the projected rates and their 95 % CI indicating no reduction. A total of 1,279 subjects were included in the postfracture care analysis. Over time, the likelihood of receiving osteoporosis care increased by 64 % (OR = 1.64, 95 % CI 1.27-2.11), and the two strongest predictors of care were female gender and corticosteroid use. Over our study period, fracture rates remained stable in this RA population. However, the use of osteoporosis drugs, BMD testing, and provision of postfracture osteoporosis care improved, which may result from gradual adoption of guidelines.

Rheumatoid arthritis pharmacotherapy and predictors of disease-modifying anti-rheumatic drug initiation in the early years of biologic use in Quebec, Canada.

Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) pharmacotherapy and should be initiated promptly after RA diagnosis. We examined trends in use of traditional and biologic DMARDs, and non-DMARD treatments, among overall RA patients, and factors associated with DMARD initiation in the newly diagnosed RA. RA subjects identified with the Quebec administrative databases were followed between January 1, 2002, and December 31, 2008. DMARD use was characterized on November 1 of each year using cross-sectional analyses. For a subgroup of newly diagnosed subjects, we used multivariable logistic regressions to identify predictors of DMARD initiation within 12 months of diagnosis and survival analyses to appraise time to DMARD initiation. A total of 37,399 subjects were included (65.8 % ≥65 years; 70.5 % female). The percentage of subjects using any DMARDs increased over the study period from 41.4 % [95 % confidence interval (CI) 40.8-42.0] to 43.3 % (95 % CI 42.7-43.9). Among newly diagnosed RA, being followed by a rheumatologist was the strongest predictor of DMARD initiation (odds ratio 4.31; 95 % CI 3.73-4.97). Care by an internist, increasing calendar year, use of NSAIDs, corticosteroids, or opioids, and a history of hospitalization increased the likelihood of DMARD initiation. Older age, female, higher comorbidity score, number of medical visits pre-diagnosis, care by other specialists, and the use of acetaminophen were inversely associated with DMARD initiation. The probability of any DMARD initiation at 12 months was 38.5 %. Despite the clinical practice guideline recommendations for earlier aggressive RA management, DMARD use appears to be suboptimal in Quebec.

Mortality and readmission rates after hospitalization for upper and lower gastrointestinal events in Quebec, Canada.

GOALS: We determined yearly rates of upper and lower gastrointestinal (GI) hospitalizations in Quebec, Canada and compared the 1-year readmission and mortality risks among those discharged from lower versus upper GI hospitalizations. BACKGROUND: The burden of serious upper and lower GI events is substantial. STUDY: Demographic, medical, pharmaceutical, and hospital records were used in a retrospective cohort study to assess risks of mortality and hospital readmission for upper and lower GI events among patients 50 years and older during 1998 to 2006. RESULTS: Among included 39,771 GI hospitalizations, 5238 were from 1998 to 1999, and 5050 from 2005 to 2006. Rates of upper GI hospitalizations decreased in the study period, whereas that of lower GI events did not change. The risk of in-hospital mortality was higher in patients with small bowel versus upper GI events [odds ratio 2.11; 95% confidence interval (CI), 1.81-2.47] and lower in patients with colon/rectal events 0.30 (0.25-0.36). One-year mortality risk after discharge was lower in patients with lower versus upper GI events (small bowel hazard ratio 0.81; 95% CI, 0.70-0.93; and colon/rectal: 0.77; 95% CI, 0.71-0.83). Compared to upper GI events, the risk of hospital readmission was higher in those with small bowel 1.53 (1.19-1.97) and similar in those with colon/rectal events 1.12 (0.96-1.31). CONCLUSIONS: The risk of upper GI events may be decreasing, but remains over 3 times as high as that of lower GI events and among those admitted for GI events, about 80% of in-hospital mortality occurred in those with upper GI problems. Although GI events in the small bowel are less frequent than those in upper or lower GI tract, they are the most severe and are associated with higher risks of mortality and hospital readmissions.

Concordance with guideline recommendations: previous and more recent nonsteroidal anti-inflammatory drug prescriptions in Quebec, Canada.

BACKGROUND: Clinical practice guidelines for appropriate nonsteroidal anti-inflammatory drug (NSAID) utilisation focus on preventing NSAID-related gastrointestinal (GI), cardiovascular (CV), congestive heart failure (CHF) and renal adverse events. We compared concordance of NSAID prescriptions with clinical practice guideline recommendations in Quebec, pre and post rofecoxib withdrawal from market. METHODS: Data were obtained from the Quebec Health Insurance Agency (RAMQ). All prescriptions for celecoxib and traditional NSAIDs (tNSAIDs) dispensed to patients ≥50 years of age were evaluated for concordance with clinical practice guidelines. Prescriptions were stratified by time period (pre and post rofecoxib withdrawal) and, GI, CV, CHF and renal risk factors at the dispensing date. Gastro-protective agent (GPA) co-prescriptions were also evaluated. RESULTS: We assessed 1,966,793 celecoxib and 1,743,481 tNSAIDs prescriptions. Of celecoxib prescriptions, 87.2% and 86.5% were appropriate in the post- and pre-periods, respectively, compared to 72.6% and 70.1% of tNSAIDs prescriptions, respectively. In logistic regression, 'appropriateness' of celecoxib prescriptions increased with age, rheumatoid arthritis and osteoarthritis (OA), and was higher in the post- versus pre-period (odds ratio 1.22, 95% confidence interval 1.18-1.26); it was lower in women and in patients with higher income. 'Appropriateness' of tNSAID prescriptions decreased in the post-period (0.92, 0.89-0.95), was lower in older persons and those with OA, and higher in women and in higher income patients. Of tNSAID prescriptions that should have received a GPA co-prescription, only 45.6% did. CONCLUSION: Concordance with guideline recommendations increased for celecoxib and decreased for tNSAIDs after rofecoxib withdrawal; GPA co-prescription with tNSAIDs remained suboptimal.

Use of nonsteroidal antiinflammatory drugs: is there a change in patient risk profile after withdrawal of rofecoxib?

OBJECTIVE: Use of traditional nonsteroidal antiinflammatory drugs (tNSAID) increased after rofecoxib withdrawal. tNSAID use is associated with increased gastrointestinal (GI) toxicity and cardiovascular (CV) risk similar to celecoxib. The objective of our study was to describe changes in celecoxib and tNSAID use regarding GI and CV risk and congestive heart failure (CHF) and renal risk that occurred in Quebec, Canada, between April 2005-March 2007 (the post-period) compared to April 2002-March 2004 (the pre-period). METHODS: Data were obtained from the provincial health insurance agency. All NSAID users ≥ 50 years of age were considered. RESULTS: Celecoxib use decreased by 23% (coxib 61%) while that of tNSAID doubled. In both periods, celecoxib users were older and included more women, and they suffered more frequently from arthritis. Users of celecoxib were more likely to have higher level of GI risk: post-period odds ratios compared to low GI risk, very high 1.79 (95% CI 1.63, 1.97), high 1.76 (95% CI 1.71, 1.81), and moderate 1.30 (95% CI 1.27, 1.33); similar results were observed in the pre-period. Celecoxib users had higher CV risk levels in the pre-period: OR compared to low CV risk, very high 1.13 (95% CI 1.08, 1.19), high 1.24 (95% CI 1.20, 1.29), and moderate 1.16 (95% CI 1.14, 1.19); and in the post-period, very high 0.85 (95% CI 0.81, 0.89), high 1.13 (95% CI 1.10, 1.16), and moderate 1.15 (95% CI 1.12, 1.17). CHF and renal risk factors did not play an important role in the choice of NSAID in either period. CONCLUSION: Current NSAID use differs from that prior to 2004. Coxib utilization decreased substantially and patients at high CV risk seem less likely to receive celecoxib, while those at high GI risk seem more likely to receive it.

Comparison of the metabolic and economic consequences of long-term treatment of schizophrenia using ziprasidone, olanzapine, quetiapine and risperidone in Canada: a cost-effectiveness analysis.

RATIONALE, AIMS AND OBJECTIVES: Second-generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long-term complications. This study evaluates the cost-effectiveness of four second-generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long-term metabolic consequences. METHOD: Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi-Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality-adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed. RESULTS: The total average cost of treatment with ziprasidone was $25,301 versus $28,563 with olanzapine, $26,233 with quetiapine and $21,831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218,060. CONCLUSION: Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine.

Cost-utility of celecoxib use in different treatment strategies for osteoarthritis and rheumatoid arthritis from the Quebec healthcare system perspective.

OBJECTIVE: To assess the cost-utility of celecoxib in three treatment strategies for arthritis in Quebec, considering both upper gastrointestinal (GI) and cardiovascular (CV) events. METHODS: A Markov analytic framework was used to model patients with osteoarthritis and rheumatoid arthritis at low/average and high risk of GI and CV toxicity over 5 years with monthly cycles. Treatment strategies were modelled in line with Canadian clinical practice. In first-line treatment, patients started on celecoxib; second-line, patients started on a non-selective non-steroidal anti-inflammatory drug (NSAID) and switched to celecoxib after a first GI event; third-line, patients started on a non-selective NSAID, added a proton pump inhibitor (PPI) after a first GI event, and switched to celecoxib after a second GI event (while maintaining the PPI). Model inputs were determined through comprehensive literature searches (MEDLINE and EMBASE) from 1995 to 2006. Included studies evaluated GI (dyspepsia, uncomplicated and complicated ulcers, death) and CV (myocardial infarction, stroke, death) events. Drug and procedure costs were derived from Canadian published sources (Can$2005). RESULTS: Total costs per patient for celecoxib first-, second-, and third-line treatment were Can$4,790, $3,390, and $3,466, and total quality-adjusted life-years (QALY) were 3.251, 3.231, and 3.230, respectively. In all risk categories, celecoxib second-line was less costly and as effective as celecoxib third-line, producing savings to the healthcare system. Although celecoxib first-line generated incremental expenditures versus celecoxib second-line, it was also more effective. The resulting cost-utility ratio for the high-risk population was Can$54,696/QALY. Based on this analytical approach, a treatment strategy where celecoxib is used before the combination of a non-selective NSAID plus a PPI possesses cost advantages for the Quebec provincial drug programme. One-way sensitivity analysis (varying GI and CV event rates, utilities, and cost) generally showed second-line treatment with celecoxib as the dominant strategy compared with third-line treatment with celecoxib. CONCLUSION: Although effectiveness of second- and third-line celecoxib use is similar, total cost is lower for second-line. These results suggest that the use of celecoxib before the combination of a non-selective NSAID plus a PPI is relatively cost-effective in the treatment of arthritis pain and support the full benefit listing of celecoxib in Quebec's drug programme.

Cost of corneal transplantation for the Quebec health care system.

OBJECTIVE: Although corneal graft is a common, long-standing procedure, little is known about its economic impact. The purpose of this study was to estimate resource use and costs associated with corneal transplantation according to a public third-party perspective. DESIGN: Retrospective study using claim data from the Régie de l'assurance maladie du Québec (RAMQ). PARTICIPANTS: A total of 610 subjects were included in the study. Mean age was 54.8 (SD 20.4) years. METHODS: The RAMQ provided medical and pharmaceutical data for a random sample of 75% of the patients who underwent a corneal graft procedure between June 1, 1999, and May 31, 2002. Resource usage data, defined as medical interventions, physician visits, and medication, were collected for a 3-year postoperative follow-up period. Hospital costs associated with corneal graft were obtained from the University of Montreal Hospital Centre costing system. RESULTS: The average costs per patient for graft and anesthesia were $501 (SD $75) and $115 (SD $124), respectively. The mean cost per patient for physician visits was $276 (SD $146). The mean number of physician visits per patient during the follow-up was 14.9 (SD 9.1). The cost per patient for medication was $337 (SD $1075). The average total cost per patient was $1229 (SD $1125). Costs incurred by the hospital represented a total of $1942. CONCLUSIONS: The overall cost of corneal graft, including a 3-year follow-up, was estimated at $3171 ($1229 RAMQ, $1942 hospital). The majority of these costs occurred at the time of the procedure.