Population-Based Study Detailing Cutaneous Melanoma Incidence and Mortality Trends in Canada.

Background: Cutaneous melanoma (CM) is one of the most fatal types of skin cancer. Alarmingly, increases in incidence and mortality were noted globally for this malignancy, despite increase in understanding of melanoma pathogenesis and enhanced prevention efforts. Methods: Data was extracted for CM patients for provinces and territories (except Quebec) using two independent, population-based registries. Analysis was performed using both clinical and pathological characteristics: tumor morphologic classification, age, sex, anatomic site affected and place of residence. Mortality trends were assessed over a 7-year period. Results were compared to prior findings for 1992-2010. Results: During 2011-2017 39,610 patients were diagnosed with CM, with 5,890 reported deaths. National crude CM incidence was 20.75 (age-standardized incidence: 14.12) cases per 100,000 individuals per year. Females accounted for 45.8% of cases and 37.1% of deaths. While CM incidence rates continue to increase in both sexes, since 2013 the CM mortality is declining. We observed important differences across the provinces/territories, where Nova Scotia, Prince Edward Island, southern Ontario/British Columbia and certain coastal communities of New Brunswick demonstrated higher CM incidence and mortality rates. The observed incidence and mortality trends for 2011-2017 validate and extend earlier observations from 1992 to 2010 for CM. Conclusion: This population-based study highlights that while melanoma's incidence is increasing in Canada, mortality rates are for the first time decreasing since 2013. We detail regional distribution of this cancer highlighting communities in southern/coastal areas, as being most at risk as well as the latest trends of melanoma incidence by age, sex and anatomic site. In males, melanoma is more common on the head/trunk, while in females on the extremities. Notably, Acral Lentiginous Melanoma was the only CM subtype that was more common in females, which primarily affects hands and feet.

Uveal melanoma incidence trends in Canada: 1992-2010 vs. 2011-2017.

Background/aims: Uveal melanoma is the most common type of non-cutaneous melanoma and the most common ocular malignancy in the adult population, especially affecting Caucasians (98% of cases). Despite its low incidence rate, we have noted increasing incidence trends in recent years. Methods: We analyzed uveal melanoma incidence data using the Canadian Cancer Registry (CCR) for 2011-2017 years. The data was examined using the International Classification of Diseases for Oncology, Third Edition, codes for all uveal melanoma subtypes. The data for 2011-2017 was then compared to previously published work by our research group for uveal melanoma incidence in Canada between 1992 and 2010 using the same methodology. Results: Between 2011 and 2017, 1,215 patients were diagnosed with uveal melanoma, 49% of whom were females. The percentage distribution of uveal melanoma between the sexes was similar between 1992-2010 and 2011-2017, whereby of the 2,215 diagnoses of uveal melanoma in 1992-2010, 47.9% were females. The change in the incidence rate for this cancer has doubled between 1992-2010 and 2011-2017, from 0.074 to 0.15 cases per million individuals per year. Our study documents that the Canadian 2011-2017 age-standardized incidence rate (ASIR) for uveal melanoma against the World Health Organization (WHO) 2000-2025 world population standard was 5.09 cases per million individuals per year (95% confidence interval, 4.73-5.44), as compared with the 1992-2010 rate of 3.34 cases per million individuals per year (95% confidence interval, CI 3.20 to 3.47). Conclusion: This work demonstrates an ongoing, steady increase in uveal melanoma incidence in Canada in recent years.

Dose specific effectiveness and safety of DOACs in patients with non-valvular atrial fibrillation: A Canadian retrospective cohort study.

BACKGROUND: Direct oral anticoagulants (DOACs) have been proven to be effective and safe for prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, suboptimal adherence, variable dosing and use in patient populations that otherwise would have been excluded from clinical trials may impact the efficacy and safety profile of DOACs in a routine care setting. We compared stroke, bleeding, and mortality rates on and off therapy for standard and low-dose DOACs (apixaban, rivaroxaban, dabigatran) versus warfarin in a Canadian cohort. We also assessed persistence of DOACs compared to warfarin. METHODS: We conducted six 1-1 propensity-score matched retrospective cohort analyses using Quebec health administrative databases (2011-2017). NVAF patients (≥18 years) covered by the public medication insurance plan entered the cohort on the first OAC dispensation date. We excluded those with OAC use in the previous year or stroke or bleeding diagnoses in the previous two years. Follow-up ended at death, March 2017 or end of medication coverage by the public plan. Time-dependent Cox regression was applied. RESULTS: We evaluated 10,893 patients initiated on apixaban (7206 standard, 3687 low-dose), 10,190 on rivaroxaban (7396 standard, 2794 low-dose), 5884 on dabigatran (2756 standard, 3128 low-dose), and propensity score-matched warfarin users. Across standard-dose DOACs, compared to warfarin, stroke risks were similar; bleeding risks were lower with apixaban (hazard ratio 0.63; 95% confidence interval 0.52-0.77) and dabigatran (0.47; 0.35-0.64) but not rivaroxaban (0.93; 0.79-1.10); death risks were lower with all DOACs. For low-dose DOACs, rivaroxaban demonstrated higher stroke (1.79; 1.21-2.64) and bleeding risks (1.37; 1.09-1.73); other agents had stroke risks similar to warfarin and bleeding risks lower than warfarin; only low-dose dabigatran had lower death risk (0.59; 0.52-0.68). Treatment discontinuation was lower with DOACs versus warfarin with the exception of low-dose rivaroxaban. The risks of stroke were 2-4 folds higher during time off any OAC versus time on warfarin. The risks of death were higher, while the risks of bleeding were generally lower during times off any OAC. CONCLUSIONS: Standard-dose DOACs had similar stroke, better persistence and mortality profiles than warfarin. Only standard dose apixaban and dabigatran had better bleeding profiles than warfarin. Low-dose rivaroxaban had worse persistence, stroke and bleeding profiles than warfarin, while low-dose apixaban and dabigatran had similar stroke and better bleeding profiles. Real-world use of DOACs may explain some of the differences observed in Canadian routine care versus the phase III clinical trials.

Non-Melanoma Skin Cancer Distribution in the Russian Federation.

BACKGROUND: Non-melanoma skin cancer (NMSC) incidence has been increasing steadily around the world. The aim of the study is to describe geographic trends in incidence and mortality of NMSC in Russia between 2007 and 2017 and compare findings to other European countries. METHODS: We used geospatial analysis to map the incident cases and descriptive statistical analysis to analyze trends. Additionally, we assessed the relationship between ethnicity, geographic latitude/longitude, and NMSC incidence/mortality rates. We retrospectively analyzed the data from the Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, for 2007-2017. Routine methods of descriptive epidemiology were used to study incidence and mortality rates by age groups, years, and jurisdictions (i.e., Federal Districts and Federal Subjects). RESULTS: In total, 733,723 patients were diagnosed with NMSC in Russia over the period 2007-2017, of whom 63% were women. The overall age-standardized incidence and mortality rates were 29.64/100,000 and 0.70/100,000, respectively. There was a consistent increase in age-standardized incidence rates over the study period, with a decreasing mortality rate. Geographic mapping revealed north-to-south and east-to-west gradients for NMSC. CONCLUSIONS: This study demonstrated longitudinal trends for NMSC incidence in Russia documenting that skin phototype, latitude/longitude, climate zones, and cultural practices remain dominant risk factors defining the epidemiology of NMSC. Moreover, this work identified several regions in the country (i.e., Republic of Adygea, Samara, Krasnodar Krai, etc.), where patient education/sun awareness campaigns will be useful to help reduce the risk of this malignancy.

Cost of Refractory Crohn's Disease Before and After Ustekinumab Utilization.

BACKGROUND: Crohn's disease (CD) is associated with major health services utilization and costs. Between 2012 and 2015, ustekinumab was used off-label in Quebec, Canada for treatment of refractory CD. AIMS: We assessed the direct medical cost of adult CD patients in the 1-year pre- and 1-year postustekinumab initiation. METHODS: Data were obtained from the provincial administrative databases. CD patients dispensed subcutaneous ustekinumab in 2012 to 2014 were followed for 1 year from the date of initiation (index-date). Kaplan Meier plots were used to display time to ustekinumab discontinuation and factors associated with discontinuation were identified using multivariate Cox regression models. Direct medical costs and 95% confidence interval (CI) of gastrointestinal-related health services were calculated for the 1-year pre- and 1-year post-index-date. RESULTS: Thirty-four CD patients (mean age ± standard deviation, 44 ± 14 years, 59% women and 41% with low income) were included. Of these, 14 (41%) discontinued ustekinumab during the postperiod. Discontinuation was less likely among older patients: hazard ratio (95% CI) per 5-year age increase, 0.77 (0.61 to 0.96). The total $CAN direct medical cost (mean, 95% CI) was higher in the post- versus preperiod: $1,681,239 ($49,448; $42,265 to $57,160) versus $880,060 ($25,884; $20,391 to 31,596), while the total costs of GI-related health services were similar: $250,206 ($7359, $3536 to $11,674), versus $213,446 ($6278, $3609 to $9423). CONCLUSION: In patients with severe refractory CD on off-label ustekinumab, approximately 60% remained on treatment beyond 1 year. The cost of gastrointestinal services did not increase during that year as compared to that of the year preceding ustekinumab use.

Comparative persistence of anti-tumor necrosis factor therapy in ankylosing spondylitis patients: a multicenter international study.

Objective: To evaluate persistence on conventional DMARDs (cDMARDs) and anti-TNF therapies, and to identify potential determinants of discontinuation among individuals with ankylosing spondylitis (AS) living in Brazil and Quebec, Canada.Methods: We conducted a cohort study of AS patients using health administrative data (2010-2015). One-year and 2-year persistence rates were assessed. Cox regression was used to identify potential determinants of therapy discontinuation.Results: One-year persistence was less likely in Brazil for both anti-TNF and cDMARDs (Brazil: 62.1 and 30.7%, Quebec: 66.9 and 67.0%). The 2-year persistence rates were lower for both anti-TNF and cDMARD, but remained higher in Quebec (Brazil: 47.9 and 18.1%, Quebec: 51.5 and 53.5%). In multivariate Cox regression analysis, age, sex and comorbidities were associated with persistence in both countries. In Quebec, persistence did not differ between rural and urban regions or with socioeconomic status. While in Brazil, patients in regions with higher Human Development Index and those in cities with lower Gini index were less likely to discontinue therapy.Conclusions: Canadian AS patients were more likely to persist on therapy compared to Brazilian patients, although rates were lower at 2 years in both countries. Socioeconomic disparity in persistence was found in Brazil, but not in Quebec.

Incidence Rates and Predictors of Colectomy for Ulcerative Colitis in the Era of Biologics: Results from a Provincial Database.

BACKGROUND: We evaluated long-term incidence and identified risk factors of colectomy in pre-biologics and biologics eras for treatment of ulcerative colitis. METHODS: After IRB approval, using data obtained from the Régie d'assurance maladie du Québec, we defined two cohorts: pre-biologics (1998-2004) and biologics (2005-2011) eras. Patients with inflammatory bowel disease or colectomy 1 year prior to first diagnosis of ulcerative colitis were excluded. Multivariate logistic regression model compared patient baseline characteristics. Kaplan-Meier curves displayed unadjusted time to event. Cox proportional hazards models were used to compare adjusted colectomy and mortality rates, respectively. RESULTS: In pre-biologics and biologics eras, 335/2829 and 314/3313 patients, respectively, underwent colectomy. Median follow-up (first and third quartiles) was similar (p = 0.206). Incidence rates for colectomy were 36.08/1000 and 29.99/1000 patient years. Unadjusted rate of colectomy was higher in pre-biologics era (p = 0.004). Predictors of colectomy included anemia (1.66; 1.38-2.01), gastrointestinal hospitalizations (1.24; 1.04-1.47), congestive heart failure (2.08; 1.27-3.40), and male gender (1.47; 1.26-1.72). Mortality was 8.06 and 3.18% in pre-biologics and biologics eras. After adjusting for potential confounders, age (1.08; 1.05-1.12) and urgent colectomy (5.65; 2.19-14.54) remained associated with increased mortality hazard. CONCLUSION: Incidence of colectomy decreased after introduction of biologics. Risk factors for colectomy were gastrointestinal hospitalizations, anemia, male gender, and congestive heart failure. Emergent surgery and age were predictors of mortality.

Vitamin B12 deficiency in inflammatory bowel disease: a prospective observational pilot study.

BACKGROUND AND AIM: Diagnostic and management guidelines for vitamin B12 (cobalamin, Cbl) deficiency in inflammatory bowel disease (IBD) are lacking. True deficiency is defined as Cbl concentrations below reference range combined with elevated methylmalonic acid (MMA) concentrations. Studies analyzing Cbl status in IBD use only Cbl concentrations without confirmatory MMA. This study aims to determine the proportion of IBD patients with Cbl concentrations below reference range and their predisposing clinical and genetic characteristics. We then compared this to the proportion with true deficiency. PATIENTS AND METHODS: In a prospective observational pilot study of adult IBD outpatients, Cbl concentrations, MMA levels, and fucosyltransferase 2 mutations were measured at clinic visits. RESULTS: A total of 66 Crohn's disease (CD) and 30 ulcerative colitis (UC) patients were recruited. Mean Cbl concentrations (pmol/l) in CD (253.7) were not significantly lower than UC (320.5, P=0.24). Serum Cbl below reference range (<148) was observed in 7.6 and 10% of CD and UC patients, respectively (P=0.70). True deficiency in CD and UC was 3 and 3.3%, respectively (P=1.0). Patients with ileal resections more than 30 cm had lower mean Cbl concentrations (177, P=0.02) and a trend toward higher proportions with Cbl levels below reference range (40%, P=0.06), but not increased deficiency rates (0%, P=1.0). Disease location, severity, and fucosyltransferase 2 mutations were not associated with altered Cbl status. CONCLUSION: True Cbl deficiency was rare in IBD patients in this study. A disparity in Cbl status exists when confirmatory MMA levels are used compared with Cbl concentrations alone. Asymptomatic IBD patients with low serum Cbl require confirmatory tests to guide management and avoid unnecessary treatment.

Cost of Ulcerative Colitis in Quebec, Canada: A Retrospective Cohort Study.

BACKGROUND: Ulcerative colitis (UC) is associated with significant health care utilization and costs. We assessed UC direct medical costs in Quebec, Canada, in 2 time periods (1998-2004 and 2005-2011) and determined changes over time. METHODS: Because the introduction of anti-tumor necrosis factor α may have influenced the UC cost, we used the Quebec health services administrative databases and the same inclusion criteria to create 2 separate UC cohorts, before (1998-2004) and after (2005-2011) anti-tumor necrosis factor α introduction. RESULTS: The postcohort included 801 patients and the precohort 716 patients. Overall, cohorts were predominately women and were comparable in terms of patient's demographics and comorbidities. Corticosteroid use, emergency department visits and hospitalizations for colectomies, and other gastrointestinal disorders were fewer in the postcohort versus precohort. The median daily cost (interquartile range) was $16.96 ($6.80-$48.16) for the postcohort and $18.65 ($7.82-$53.31) for the precohort. In generalized linear models with log link and gamma distribution, the adjusted daily cost ratios (95% confidence interval) in the postcohort versus precohort was 0.75 (0.67-0.85). Older age at inclusion, low income, lower socioeconomic status, and previous use of gastroprotective agents, antidepressants, and sulfasalazine, methotrexate, or cyclosporine were associated with increased costs. Women and those who visited a gastroenterologist in the previous year incurred lower costs. CONCLUSIONS: The mean UC daily cost decreased from 2005 to 2011 as compared to 1998 to 2004 because of a decrease in rates of colectomy and other gastrointestinal hospitalizations and emergency department visits. Further investigation is required to determine the reasons for these changes.

Hospitalization for musculoskeletal disorders in rheumatoid arthritis patients: a population-based study.

BACKGROUND: Rheumatoid arthritis (RA) patients failing disease modifying antirheumatic drugs (DMARDs) may undergo anti-Tumor Necrosis Factor (anti-TNF) therapy. Using the Quebec health services administrative databases, we examined the rates of musculoskeletal (MSD)-related hospitalizations among RA patients receiving anti-TNF, DMARDs, and neither of those therapies (non-users). METHODS: Matched cohort analyses were performed separately in 2002-2006 and 2007-2011. In each cohort, DMARD and non-user groups were formed to 3-1 match the anti-TNF users on age, sex, date of RA diagnosis, high-dimensional propensity score and date of the first anti-TNF dispensation (index-date). Non-users did not use DMARDs or anti-TNF drugs during the year before the index-date and in the 90 days post, but used at least one of these medications in the study period. RESULTS: During 2002-2006, 557 anti-TNF users were matched to 1144 DMARD users and to 656 non-users, compared to 690, 1651, and 532 patients, respectively during 2007-2011. The crude rates of MSD-related hospitalizations in the anti-TNF, DMARD and non-users groups were respectively: 8.2/100, 6.4/100 and 10.5/100 patient-years in 2002-2006, and 6.9/100, 4.8/100, and 8.6/100 patient-years in 2007-2011. In multivariable Cox regression models, the hazard ratios of MSD-related hospitalizations (95 % confidence interval) were: 0.95 (0.60; 1.50) for anti-TNF and 0.69 (0.46; 1.02) for DMARD users, versus non-users in 2002-06, and 0.65 (0.37; 1.14) and 0.40 (0.24; 0.66), respectively in 2007-2011. CONCLUSION: The MSD-related hospitalization risk was lower in RA patients using DMARD therapy and similar in those using anti-TNF therapy with or without DMARDs as compared to those not using either of these therapies during the study period.

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.

Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction.

BACKGROUND: Patients prescribed antiplatelet treatment to prevent recurrent acute myocardial infarction are often also given a selective serotonin reuptake inhibitor (SSRI) to treat coexisting depression. Use of either treatment may increase the risk of bleeding. We assessed the risk of bleeding among patients taking both medications following acute myocardial infarction. METHODS: We conducted a retrospective cohort study using hospital discharge abstracts, physician billing information, medication reimbursement claims and demographic data from provincial health services administrative databases. We included patients 50 years of age or older who were discharged from hospital with antiplatelet therapy following acute myocardial infarction between January 1998 and March 2007. Patients were followed until admission to hospital due to a bleeding episode, admission to hospital due to recurrent acute myocardial infarction, death or the end of the study period. RESULTS: The 27,058 patients in the cohort received the following medications at discharge: acetylsalicylic acid (ASA) (n = 14,426); clopidogrel (n = 2467), ASA and clopidogrel (n = 9475); ASA and an SSRI (n = 406); ASA, clopidogrel and an SSRI (n = 239); or clopidogrel and an SSRI (n = 45). Compared with ASA use alone, the combined use of an SSRI with antiplatelet therapy was associated with an increased risk of bleeding (ASA and SSRI: hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.08-1.87; ASA, clopidogrel and SSRI: HR 2.35, 95% CI 1.61-3.42). Compared with dual antiplatelet therapy alone (ASA and clopidogrel), combined use of an SSRI and dual antiplatelet therapy was associated with an increased risk of bleeding (HR 1.57, 95% CI 1.07-2.32). INTERPRETATION: Patients taking an SSRI together with ASA or dual antiplatelet therapy following acute myocardial infarction were at increased risk of bleeding.

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.

Discrepancy among observational studies: example of naproxen-associated adverse events.

BACKGROUND: Observational studies assessing the cardiovascular adverse effect of naproxen have had conflicting results. It is not clear whether variation in population characteristics between studies may explain some of this discrepancy. OBJECTIVE: To determine whether changes in patient characteristics of naproxen users occurred between 1999 and 2004 in Québec, Canada and to examine whether these temporal changes were accompanied by changes in estimates of naproxen-related hospitalizations for gastrointestinal (GI) ulcers and myocardial infarction, using provincial health services administrative databases. METHODS: Demographic, pharmaceutical and physician billing records of patients 65 years and older, who received naproxen or acetaminophen prescriptions between 1999 and 2004 were used. Two identical cohort studies, labeled Study 1 and Study 2 were conducted and their results were compared. One study was confined to the time period 1999-2001 and the other to 2002-2004. Patient characteristics at index date (the date of the first naproxen or acetaminophen prescription during the corresponding period) were compared between the study cohorts in naproxen and acetaminophen users, respectively, and within each study cohort between naproxen and acetaminophen users, using logistic regression models. Cox regression models with time dependent exposure were used to assess the association between naproxen vs acetaminophen and hospitalizations for GI events or AMI, respectively within each study. Results were then compared between the two studies. RESULTS: Study 1 (1999-2001) cohort included 240,568 patients (205,238 acetaminophen and 35,330 naproxen) and Study 2 (2002-2004) cohort included 213,802 patients (193,918 acetaminophen and 19,884 naproxen). Patient characteristics of naproxen and acetaminophen users differed between the two studies. Naproxen users in Study 2 vs Study 1 were slightly younger, less likely to be females, less likely to have concomitant GI disease, less likely to have osteoarthritis and other co-morbidities and more likely to have used proton pump inhibitors, antihypertensive agents, anticoagulants, clopidogrel and aspirin. In general, similar changes in patient characteristics were observed in acetaminophen users between the two study cohorts. Compared to acetaminophen (without aspirin), the estimates of the GI risks with naproxen whether, used with or without aspirin, were significantly higher in Study 2 vs Study 1 [Hazard Ratio (HR) (95% CI): 4.94 (3.48, 7.02)] vs [2.22 (1.62, 3.06)], naproxen with aspirin [4.94 (2.93, 8.33) vs 2.47 (1.48, 4.12)], and acetaminophen and aspirin: [2.31 (1.89, 2.82) vs 1.46 (1.20, 1.77)]. The estimate of the AMI risk with naproxen also seemed to be higher in Study 2 vs Study 1, however the increase was not statistically significant [HR (95% CI) in the naproxen group: 1.18 (0.83, 1.67) in Study 1 vs 0.94 (0.70, 1.25) in Study 2], naproxen with aspirin. [1.44 (0.95, 2.18) vs 1.05 (0.68, 1.61)]; and acetaminophen and aspirin. 1.15 (1.01, 1.30) vs 1.10 (0.97, 1.26). CONCLUSION: Variation in patient characteristics in naproxen users was observed between 1999 and 2004. This variation was likely to be accompanied by a variation in patient pre-disposition to GI events that may explain the increase in estimates of naproxen-related GI adverse events observed during this period.

Long-term prognosis of south Asians following acute coronary syndromes.

BACKGROUND: South Asians (SAs) have a higher prevalence of coronary artery disease than Caucasians. The long-term prognosis following acute coronary syndromes (ACS) in SA compared with non-SA patients is unclear. OBJECTIVES: To compare the long-term adverse cardiovascular outcomes between SA and non-SA patients who have ACS. METHODS: A case-control study of 65 consecutive SA patients admitted with ACS to the McGill University Health Centre (Montreal, Quebec) between 1995 and 2000 was conducted. Control subjects included 65 non-SA patients admitted to the same hospital with ACS matched by age, sex and year of hospitalization. RESULTS: The mean +/- SD age was 59.7+/-9.9 years and 12% of patients were women. There were more cases of diabetes mellitus among the SA patients than non-SA patients (43% versus 23%, respectively). Only 19% of SA patients were active smokers, compared with 34% of non-SA patients. At one year, 35% of SA patients had undergone coronary artery bypass graft surgery, compared with 22% of non-SA patients. One-year mortality was increased among the SA patients compared with the non-SA patients (6% versus 2%, respectively). However, SA ethnicity was not an independent predictor of one-year adverse cardiovascular outcomes. CONCLUSIONS: The present study demonstrated an increased prevalence of diabetes mellitus among the SA patients with ACS compared with non-SA patients. SA patients had increased one-year mortality compared with non-SA patients. However, SA ethnicity was not an independent predictor of one-year mortality and coronary intervention.

Postdischarge thromboprophylaxis and mortality risk after hip-or knee-replacement surgery.

BACKGROUND: Patients undergoing hip or knee replacement are at high risk of developing a postoperative venous thromboembolism even after discharge from hospital. We sought to identify hospital and patient characteristics associated with receiving thromboprophylaxis after discharge and to compare the risk of short-term mortality among those who did or did not receive thromboprophylaxis. METHODS: We conducted a retrospective cohort study using system-wide hospital discharge summary records, physician billing information, medication reimbursement claims and demographic records. We included patients aged 65 years and older who received a hip or knee replacement and who were discharged home after surgery. RESULTS: In total we included 10 744 patients. Of these, 7058 patients who received a hip replacement and 3686 who received a knee replacement. The mean age was 75.4 (standard deviation [SD] 6.8) years and 38% of patients were men. In total, 2059 (19%) patients received thomboprophylaxis at discharge. Patients discharged from university teaching hospitals were less likely than those discharged from community hospitals to received thromboprophylaxis after discharge (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-1.00). Patients were less likely to receive thromboprophylaxis after discharge if they had a longer hospital stay (15-30 days v. 1-7 days, OR 0.69, 95% CI 0.59-0.81). Patients were more likely to receive thromboprophylaxis if they had hip (v. knee) replacement, osteoarthritis, heart failure, atrial fibrillation or hypertension, higher (v. lower) income or if they were treated at medium-volume hospitals (69-116 hip and knee replacements per year). In total, 223 patients (2%) died in the 3-month period after discharge. The risk of short-term mortality was lower among those who received thromboprophylaxis after discharge (hazard ratio [HR] 0.34, 95% CI 0.20-0.57). INTERPRETATION: Fewer than 1 in 5 elderly patients discharged home after a hip-or knee-replacement surgery received postdischarge thromboprophylaxis. Those prescribed these medications had a lower risk of short-term mortality. The benefits of and barriers to thromboprophylaxis therapy after discharge in this population requires further study.

Hospitalizations for upper and lower GI events associated with traditional NSAIDs and acetaminophen among the elderly in Quebec, Canada.

BACKGROUND: The risk of upper/lower gastrointestinal (GI) adverse events associated with the concomitant use of traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) with acetaminophen has not been assessed. Among users of these drugs, the concomitant use of proton pump inhibitors (PPIs) with tNSAIDs may reduce the risk of upper GI adverse events, but its effect on lower GI events is not clear. OBJECTIVE: To compare the rates of GI hospitalization (ulceration, perforation, or bleeding in the upper or lower GI tract) among elderly patients taking tNSAIDs or the combination of a tNSAID and acetaminophen with and without a PPI versus those taking acetaminophen alone. METHODS: We conducted a population-based retrospective cohort study using data obtained from the government of Quebec health insurance agency databases and the hospital discharge summary database. Patients of 65 yr of age or older who filled a prescription for acetaminophen or a tNSAID between January 1998 and December 2004 were entered in the cohort at the date of the first filled prescription from either of these medications (index date). Follow-up ended at the first date of a GI hospitalization, death, or the end of the study period. RESULTS: The cohort included 644,183 elderly patients. These patients received 1,778,541 prescriptions for tNSAIDs (315,222, 17.7% with a PPI), 158,711 for the combination of a tNSAID and acetaminophen (40,797, 25.7% with a PPI), 1,597,725 for acetaminophen (> 3 g/day) (504,939, 31.6% with a PPI), and 3,641,140 for acetaminophen (< or = 3 g/day) (1,031,939, 28.3% with a PPI). Using Cox regression models that adjusted for time-dependent variables (aspirin, anticoagulants, and clopidogrel) and other fixed patient baseline characteristics, we found similar risks of GI hospitalizations among time periods when patients were exposed to either a tNSAID with a PPI, acetaminophen (> 3 g/day) with a PPI, or acetaminophen (< or = 3 g/day) with a PPI. The risk of GI hospitalization among users of PPIs during exposure to the combination of acetaminophen with a tNSAID was twice as high as that of the reference category, acetaminophen (< or = 3 g/day) without a PPI (hazard ratio [HR] 2.15, 95% confidence interval [CI][1.35-3.40]). Among nonusers of PPIs, the risk of GI hospitalization was 1.20 (1.03-1.40) during exposure to acetaminophen (> 3 g/day), 1.63 (1.44-1.85) during exposure to tNSAIDs, and 2.55 (1.98-3.28) during exposure to the combination of a tNSAID and acetaminophen compared with the reference category. CONCLUSION: Among elderly patients requiring analgesic/anti-inflammatory treatment, use of the combination of a tNSAID and acetaminophen may increase the risk of GI bleeding compared with either agent alone.

Risks of suicide and poisoning among elderly patients prescribed selective serotonin reuptake inhibitors: a retrospective cohort study.

BACKGROUND: Treatment with selective serotonin reuptake inhibitors (SSRIs) has been associated with increased suicide risk. Risks of suicide death and of poisoning were compared during periods of SSRI treatment versus periods without any antidepressant treatment among elderly patients. METHOD: In this retrospective cohort study, records from the Quebec Health Care Fund and Vital Statistics databases were obtained for patients 65 years and older who had filled a prescription for an SSRI between January 1998 and December 2004. Patients were followed from the filling date of the first SSRI prescription during the study period until death, the end of the first period extending for at least 365 days with no antidepressant supply, or December 31, 2004, whichever occurred first. RESULTS: The cohort included 128,229 patients (mean age = 75.4 years), 70% of whom were women. Numbers of suicide deaths (crude rate/100,000 patient-years) were 37 (23) during SSRI use, 16 (51) during other antidepressant use, 5 (54) during use of both an SSRI and another anti-depressant, and 29 (29) during no antidepressant use. The adjusted risk of suicide death (Cox regression model with time-dependent exposure) was not higher during SSRI use versus nonuse (hazard ratio [95% CI]): any SSRI = 0.64 (0.38 to 1.07), paroxetine = 0.71 (0.37 to 1.35), citalopram = 1.16 (0.59 to 2.25), and sertraline = 0.38 (0.16 to 0.93). The adjusted hazard ratio (95% CI) of poisoning was higher during SSRI use versus nonuse (1.16 [1.07 to 1.25]) and varied between SSRI agents from 0.93 (0.74 to 1.16) for fluoxetine to 1.45 (1.23 to 1.71) for fluvoxamine. CONCLUSION: Among elderly patients dispensed SSRIs, the risk of suicide death was not higher during periods of SSRI use compared to when antidepressants were not being used.