Clinically Apparent Arterial Thrombosis in Persons with Systemic Vasculitis.

OBJECTIVE: To estimate the incidence rate of clinically apparent arterial thrombotic events and associated comorbidities in patients with primary systemic vasculitis. METHODS: Using large cohort administrative data from Quebec, Canada, we identified patients with vasculitis, including polyarteritis nodosa (PAN) and granulomatosis with polyangiitis (GPA). Incident acute myocardial infarctions (AMIs) and cerebrovascular accidents (CVAs) after the diagnosis of vasculitis were ascertained in the PAN and GPA group via billing and hospitalization data. These were compared to rates of a general population comparator group. The incidences of comorbidities (type 2 diabetes mellitus, dyslipidemia, and hypertension) were also collected. RESULTS: Among the 626 patients identified with vasculitis, 19.7% had PAN, 2.9% had Kawasaki disease, 23.8% had GPA, 52.4% had GCA, and 1.3% had Takayasu arteritis. The AMI rate was substantially higher in males aged 18-44 with PAN, with rates up to 268.1 events per 10,000 patient years [95% CI 67.1-1070.2], approximately 30 times that in the age- and sex-matched control group. The CVA rate was also substantially higher, particularly in adults aged 45-65. Patients with vasculitis had elevated incidences of diabetes, dyslipidemia, and hypertension versus the general population. CONCLUSION: Atherothrombotic rates were elevated in patients identified as having primary systemic vasculitis. While incident rates of cardiovascular comorbidities were also increased, the substantial elevation in AMIs seen in young adults suggests a disease-specific component which requires further investigation.

Association of smoking with cutaneous manifestations in systemic lupus erythematosus.

OBJECTIVE: To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE). METHODS: We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data. RESULTS: In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials. CONCLUSION: Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Bayesian estimation of the probability of asbestos exposure from lung fiber counts.

Asbestos exposure is a well-known risk factor for various lung diseases, and when they occur, workmen's compensation boards need to make decisions concerning the probability the cause is work related. In the absence of a definitive work history, measures of short and long asbestos fibers as well as counts of asbestos bodies in the lung can be used as diagnostic tests for asbestos exposure. Typically, data from one or more lung samples are available to estimate the probability of asbestos exposure, often by comparing the values with those from a reference nonexposed population. As there is no gold standard measure, we explore a variety of latent class models that take into account the mixed discrete/continuous nature of the data, that each subject may provide data from more than one lung sample, and that the within-subject results across different samples may be correlated. Our methods can be useful to compensation boards in providing individual level probabilities of exposure based on available data, to researchers who are studying the test properties for the various measures used in this area, and more generally, to other test situations with similar data structure.

Behavioural interventions for smoking cessation: a meta-analysis of randomized controlled trials.

AIMS: Widely varying estimates of treatment effects have been reported in randomized controlled trials (RCTs) investigating the efficacy of behavioural interventions for smoking cessation. Previous meta-analyses investigating behavioural interventions have important limitations and do not include recently published RCTs. We undertook a meta-analysis of RCTs to synthesize the treatment effects of four behavioural interventions, including minimal clinical intervention (brief advice from a healthcare worker), and intensive interventions, including individual, group, and telephone counselling. METHODS AND RESULTS: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline, and PsycINFO databases. We included only RCTs that reported biochemically validated smoking cessation outcomes at 6 and/or 12 months after the target quit date. Outcomes were aggregated using hierarchical Bayesian random-effects models. We identified 50 RCTs, which randomized n = 26 927 patients (minimal clinical intervention: 9 RCTs, n = 6456; individual counselling: 23 RCTs, n = 8646; group counselling: 12 RCTs, n = 3600; telephone counselling: 10 RCTs, n = 8225). The estimated mean treatment effects were minimal clinical intervention [odds ratio (OR) 1.50, 95% credible interval (CrI) 0.84-2.78], individual counselling (OR 1.49, 95% CrI 1.08-2.07), group counselling (OR 1.76, 95% CrI 1.11-2.93), and telephone counselling (OR 1.58, 95% CrI 1.15-2.29). CONCLUSION: Intensive behavioural interventions result in substantial increases in smoking abstinence compared with control. Although minimal clinical intervention may increase smoking abstinence, there is insufficient evidence to draw strong conclusions regarding its efficacy.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials.

BACKGROUND: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation. METHODS: We searched the US Centers for Disease Control and Prevention's Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention. RESULTS: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13), bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR 1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09-4.08). INTERPRETATION: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

Socioeconomic status, access to health care, and outcomes after acute myocardial infarction in Canada's universal health care system.

BACKGROUND: There is a debate as to whether universal drug coverage confers similar access to care at all socioeconomic status (SES) levels. Experiences in Canada may bring light to questions raised regarding access. OBJECTIVE: To assess associations between SES and access to cardiac care and outcomes in Canada's universal health care system. DESIGN, SETTING, AND PATIENTS: All patients admitted to acute care hospitals in Quebec (QC), Ontario (ON), and British Columbia (BC), between 1996 and either 2000 (QC) or 2001 (ON, BC) with acute myocardial infarction, were identified using provincial government administrative databases (n = 145,882). MEASUREMENTS: Variables representing SES grouped at the census area level were examined in association with use of cardiac medications and procedures, survival, and readmission, while adjusting for individual-level variables. A Bayesian hierarchical logistic regression model was used to account for the nested structure of the data. RESULTS: Despite provincial variations in SES and drug reimbursement policies, there were generally no associations between the SES variables and access to cardiac medications or invasive cardiac procedures. The few exceptions were not consistent across SES indicators and/or provinces. Similarly, the only observed effect of SES on clinical outcomes was in BC, where there was increased 1-year mortality among patients living in less-affluent regions (adjusted odds ratios per standard deviation change in proportion of low-income households, 95% Bayesian credible intervals, QC: 1.09, 0.96-1.25; ON: 1.02, 0.95-1.08; and BC: 1.18, 1.09-1.28). CONCLUSIONS: These results suggest that intermediary factors other than SES, such as cardiovascular risk factors, likely account for observed "wealth-health" gradients in Canada. Implementation of a universal drug coverage policy could decrease socioeconomic disparities in access to health care.

Bayesian modelling of imperfect ascertainment methods in cancer studies.

Tumour registry linkage, chart review and patient self-report are all commonly used ascertainment methods in cancer epidemiology. These methods are used for estimating the incidence or prevalence of different cancer types in a population, and for investigating the effects of possible risk factors for cancer. Tumour registry linkage is often treated as a gold standard, but in fact none of these methods is error free, and failure to adjust for imperfect ascertainment can lead to biased estimates. This is true both if the goal of the study is to estimate the properties of each ascertainment type, or if it is to estimate cancer incidence or prevalence from one or more of these methods. Although rarely applied in the literature to date, when cancer is ascertained by three or more methods, standard latent class models can be used to estimate cancer incidence or prevalence while adjusting for the estimated imperfect sensitivities and specificities of each ascertainment method. These models, however, do not account for variations in these properties across different cancer sites. To address this problem, we extend latent class methodology to include a hierarchical component, which accommodates different ascertainment properties across cancer sites. We apply our model to a data set of 169 lupus patients with three ascertainment methods and eight cancer types. This allows us to estimate the properties of each ascertainment method without assuming any to be a gold standard, and to calculate a standardized incidence ratio for cancer for lupus patients compared to the general population. As our data set is small, we also illustrate the effects as more data become available. We show that our model produces parameter estimates that are substantially different from the currently most popular method of ascertainment, which uses tumour registry data alone.

Universal health insurance coverage does not eliminate inequities in access to cardiac procedures after acute myocardial infarction.

BACKGROUND: It remains unclear whether socioeconomic status (SES) influences access to invasive cardiac procedures after acute myocardial infarction (AMI) in a universal health care system. The objective of this study was to evaluate the effect of SES on access to cardiac procedure after AMI in a universal health care system. METHODS: This was an observational cohort study of all patients with a first AMI in the province of Quebec, Canada, between 1985 to 1995. Information on treatment was obtained from the discharge and physicians' claims databases. SES was obtained from census data by linking postal codes. SES-independent predictors of use were identified, then incorporated in hierarchical models to predict use in low, medium, and high SES areas. The main outcome measures were rates of cardiac catheterization, percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABG) as a function of SES. RESULTS: SES data were available for 62,364 individuals with a first AMI. Of these, 65% were men and the mean age was 64 +/- 13 years. Rates of cardiac procedures rose with an increase in several SES measures. After adjustment for individual-level predictors of use of cardiac catheterization, average rent, (odds ratio per $100 difference: 1.57, 95% credible interval: 1.36 to 1.80) and proportion of renters, (odds ratio, 2.2; 95% CI: 1.21 to 3.73) in the area were independent SES predictors. Patients in low SES areas (median family income: $ 30,809 CDN) were less likely to undergo cardiac catheterization than patients in high SES areas ($92,169 CDN) (men: 33%; compared with 47%; women: 18%; compared with 47%). However, among patients with cardiac catheterization, SES was not associated with the use of revascularization procedures. For example, PCI rates for men within 90 days after AMI were 26%, compared with 25% in low and high SES areas, respectively. CABG rates were 15%, compared with 19%. CONCLUSIONS: We found that in the universal health care system of Canada, access to cardiac catheterization after AMI varied according to SES. Among those with cardiac catheterization, SES did not appear to influence further use of revascularization procedures.

Evidence for use of coronary stents. A hierarchical bayesian meta-analysis.

BACKGROUND: Coronary stents are widely used in interventional cardiology, but a current quantitative systematic overview comparing routine coronary stenting with standard percutaneous transluminal coronary angioplasty (PTCA) and restricted stenting (provisional stenting) has not been published. PURPOSE: To summarize results from all randomized clinical trials comparing routine coronary stenting with standard PTCA. DATA SOURCES: Electronic databases were searched by using the key words angioplasty and stent. References from identified articles were also reviewed. In addition, several prominent general medical and cardiology journals were searched and agencies known to perform systematic reviews were consulted. STUDY SELECTION: All comparative randomized clinical trials were included, except those involving primary angioplasty for the treatment of acute myocardial infarction. DATA EXTRACTION: A specified protocol was followed, and two of the authors independently extracted the data. Outcomes assessed were total mortality, myocardial infarction, angiographic restenosis, coronary artery bypass surgery, repeated PTCA, and freedom from angina. DATA SYNTHESIS: The results were synthesized by using a Bayesian hierarchical random-effects model. A total of 29 trials involving 9918 patients were identified. There was no evidence for a difference between routine coronary stenting and standard PTCA in terms of deaths or myocardial infarctions (odds ratio, 0.90 [95% credible interval [CrI], 0.72 to 1.11]) or the need for coronary artery bypass surgery (odds ratio, 1.01 [CrI, 0.79 to 1.31]). Coronary stenting reduced the rate of restenosis (odds ratio, 0.52 [CrI, 0.37 to 0.69]) and the need for repeated PTCA (odds ratio, 0.59 [CrI, 0.50 to 0.68]). The trials showed a wide range of crossover rates from PTCA to stenting. By use of a multiplicative model, each 10% increase in crossover rate decreased the need for repeated angioplasty by approximately 8% (odds ratio multiplying factor, 1.08 [CrI, 0.98 to 1.18]). Routine stenting probably reduces the need for repeated angioplasty by fewer than 4 to 5 per 100 treated persons compared with PTCA with provisional stenting. Studies were not blinded and suggest a bias with a possible overestimation of this benefit. CONCLUSIONS: In the controlled environment of randomized clinical trials, routine coronary stenting is safe but probably not associated with important reductions in rates of mortality, acute myocardial infarction, or coronary artery bypass surgery compared with standard PTCA with provisional stenting. Coronary stenting is associated with substantial reductions in angiographic restenosis rates and the subsequent need for repeated PTCA, although this benefit may be overestimated because of trial designs. The incremental benefit of routine stenting for reducing repeated angioplasty diminishes as the crossover rate of stenting with conventional PTCA increases.

Timing of total joint replacement affects clinical outcomes among patients with osteoarthritis of the hip or knee.

OBJECTIVE: To determine the predictors of outcome in patients with osteoarthritis 2 years after receiving total hip or knee replacement. METHODS: A prospective cohort study of 222 osteoarthritis patients undergoing total hip or knee replacement in Boston and Montreal was done. Their postoperative outcomes at 6 months were previously reported. This followup reports on the outcomes after 2 years among the 165 patients (74%) who remained. The subjects were divided into 2 groups according to the median value of their preoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score. The Short Form 36-item physical function subscale and the WOMAC pain and function subscale scores were collected at baseline and at 3, 6, and 24 months postoperatively. Clinical outcomes were analyzed at 2 years, using descriptive and multiple regression analyses. RESULTS: Improvements in pain and function at 2 years were similar to those observed at 6 months. Those subjects with the worst function and pain at the time of surgery (baseline) had comparatively worse function 2 years after surgery. CONCLUSION: In this comparison, the poor outcomes observed at 6 months following total joint replacement in patients with worse baseline functional status persisted after 2 years. Although there are no validated indications for when a patient should optimally have total joint replacement, these data suggest that timing of surgery may be more important than previously realized and, specifically, that performing surgery earlier in the course of functional decline may be associated with better outcome.