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Systemic treatment patterns and related mental health disorders and economic burden among patients with psoriasis are largely unknown.To assess systemic treatment patterns and associated depression and anxiety-related health care costs among patients with psoriasis initiating a conventional systemic treatment (CST).Using a retrospective cohort design with sequence and cluster analyses, we assessed systemic treatment trajectories (CST and tumor necrosis factor inhibitors or ustekinumab, [TNFi/UST]) over a 2-year period following CST initiation. We compared health care costs between trajectories using 2-part models.We included 781 patients and identified 8 trajectories: persistent methotrexate users, persistent acitretin users, early CST discontinuation, late methotrexate discontinuation, switch to TNFi/UST, adding TNFi/UST, discontinuation then restart on methotrexate, and discontinuation then restart on acitretin or multiple CST switches. Overall, 165 (21%) patients incurred depression- and anxiety-related health care costs (median annual cost, CAN$56; quartiles, $14-$127). Compared with persistent methotrexate users, adding a TNFi/UST (cost ratio, 3.63; 95% CI, 1.47-5.97) and discontinuation then restart on acitretin or multiple switches between systemic agents (cost ratio, 13.3; 95% CI 5.76-22.47) had higher costs.Trajectory misclassification may have occured. These date represent an association, and causality cannot be inferred, particularly given the risk of confounding.Depression- and anxiety-related health care costs were high among patients adding TNFi/UST and those discontinuing then restarting on acitretin or experiencing multiple switches between systemic agents.

Statins are widely prescribed for the prevention of cardiovascular (CV) events. Our objective was to describe the characteristics of patients newly prescribed a statin by general practitioners and assess the concordance of prescribing with national guidelines. Patients who were 18 years or older, French-speaking, available for the 2-year study duration, and had no history of statin use were recruited. Biological parameters were measured, and medical history, sociodemographic characteristics, and health behaviours were recorded using structured questionnaires. Patients’ eligibility for a statin was assessed using the Canadian Cardiovascular Society’s dyslipidemia guidelines. Of the 1631 new statin-users enrolled, 47.6% were women. The mean age for all patients was 57.4 years. According to the Canadian guidelines, 50.6% of patients were considered at high risk for a CV event or had a statin-indicated condition. Moderate and low-risk patients represented 26.7 and 22.7% of patients, respectively.

Background The period of time during which a patient is exposed to a drug does not necessarily correspond to the period during which the drug produces the adverse effect under consideration. We propose the term Pharmacologically pertinent period of effect (PPPE) to address this time window. We explored the PPPE in light of the rofecoxib saga. Methods We identified the observational database studies of rofecoxib at doses 25 and 50 mg daily and thromboembolic events. We also obtained the Kaplan‐Meier curves of Vioxx Gastrointestinal Outcomes Research trial (VIGOR) and Adenomatous Polyp Prevention on Vioxx (APPROVE) trials. Results We found seven observational studies with nine analyses. All the studies only looked at current exposure. At the dose of 25 mg, only three of nine analyses were barely statistically significant. At the dose of 50 mg, the risk ratios were much higher. The visual inspection of the Kaplan‐Meier curves shows that in the APPROVE trial (25 mg), the placebo and rofecoxib curves start separating to become statistically significantly different only after 36 months. In contrast the VIGOR (50 mg), curves start separating very early and the divergence increases after 8 months. Discussion The 50 mg observational studies, looking at current exposure, correctively identified the almost immediate increase in risk evident in the VIGOR Kaplan‐Meier curves. The absence of an immediate increase in risk shown by the APPROVE trial was also correctively identified by most observational 25 mg studies. To our knowledge no observational study was done on the long‐term cardiac toxicity of the 25‐mg dose. It would thus appear that the two doses of rofecoxib have different PPPEs.

Objectives To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson’s disease (PD). Study designs and Settings Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors’ strengths, different priors, and Bayesian meta-analysis Results The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively. Conclusion While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses.

OBJECTIVES: (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)–defined AKI alters the association. METHODS: A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS: The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46–6.57] and 3.38 [1.63–7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS: AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships

Background and objectives Little is known about the long-term burden of AKI in the pediatric intensive care unit. We aim to evaluate if pediatric AKI is associated with higher health service use post–hospital discharge. Design, setting, participants, & measurements This is a retrospective cohort study of children (≤18 years old) admitted to two tertiary centers in Montreal, Canada. Only the first admission per patient was included. AKI was defined in two ways: serum creatinine alone or serum creatinine and/or urine output. The outcomes were 30-day, 1-year, and 5-year hospitalizations, emergency room visits, and physician visits per person-time using provincial administrative data. Univariable and multivariable Poisson regression were used to evaluate AKI associations with outcomes. Results A total of 2041 children were included (56% male, mean admission age 6.5±5.8 years); 299 of 1575 (19%) developed AKI defined using serum creatinine alone, and when urine output was included in the AKI definition 355 of 1622 (22%) children developed AKI. AKI defined using serum creatinine alone and AKI defined using serum creatinine and urine output were both associated with higher 1- and 5-year hospitalization risk (AKI by serum creatinine alone adjusted relative risk, 1.42; 95% confidence interval, 1.12 to 1.82; and 1.80; 1.54 to 2.11, respectively [similar when urine output was included]) and higher 5-year physician visits (adjusted relative risk, 1.26; 95% confidence interval, 1.14 to 1.39). AKI was not associated with emergency room use after adjustments. Conclusions AKI is independently associated with higher hospitalizations and physician visits postdischarge.

Purpose High-dimensional propensity scores (hdPS) can adjust for measured confounders, but it remains unclear how well it can adjust for unmeasured confounders. Our goal was to identify if the hdPS method could adjust for confounders which were hidden to the hdPS algorithm. Method The hdPS algorithm was used to estimate two hdPS; the first version (hdPS-1) was estimated using data provided by 6 data dimensions and the second version (hdPS-2) was estimated using data provided from only two of the 6 data dimensions. Two matched sub-cohorts were created by matching one patient initiated on a high-dose statin to one patient initiated on a low-dose statin based on either hdPS-1 (Matched hdPS Full Info Sub-Cohort) or hdPS-2 (Matched hdPS Hidden Info Sub-Cohort). Performances of both hdPS were compared by means of the absolute standardized differences (ASDD) regarding 18 characteristics (data on seven of the 18 characteristics were hidden to the hdPS algorithm when estimating the hdPS-2). Results Eight out of the 18 characteristics were shown to be unbalanced within the unmatched cohort. Matching on either hdPS achieved adequate balance (i.e., ASDD

Unmeasured confounding is a major threat to the validity of pharmacoepidemiological studies of medication safety and effectiveness. We propose a new method for detecting and reducing the impact of unobserved confounding in large observational database studies. The method uses assumptions similar to the prescribing preference-based instrumental variable (IV) approach. Our method relies on the new ‘missing cause’ principle, according to which the impact of unmeasured confounding by (contra-)indication may be detected by assessing discrepancies between the following: (i) treatment actually received by individual patients and (ii) treatment that they would be expected to receive based on the observed data. Specifically, we use the treatment-by-discrepancy interaction to test for the presence of unmeasured confounding and correct the treatment effect estimate for the resulting bias. Under standard IV assumptions, we first proved that unmeasured confounding induces a spurious treatment-by-discrepancy interaction in risk difference models for binary outcomes and then simulated large pharmacoepidemiological studies with unmeasured confounding. In simulations, our estimates had four to six times smaller bias than conventional treatment effect estimates, adjusted only for measured confounders, and much smaller variance inflation than unbiased but very unstable IV estimates, resulting in uniformly lowest root mean square errors. The much lower variance of our estimates, relative to IV estimates, was also observed in an application comparing gastrointestinal safety of two classes of anti-inflammatory drugs. In conclusion, our missing cause-based method may complement other methods and enhance accuracy of analyses of large pharmacoepidemiological studies. Copyright © 2016 John Wiley & Sons, Ltd.

We recently conducted two economic evaluations of a hypothetical pharmacogenomic test for statin-induced myopathy (SIM) in patients at high cardiovascular risk. Although the models differed in modeling technique and data inputs, both yielded similar results. We believe our approach to assessing the economic value of a diagnostic test was highly advantageous as it characterized the complete range of false-negative and false-positive test outcomes. We used a broad interpretation of test parameters that reflected physician and patient behavioral responses to the test results and accounted for patient adherence to treatment. Both economic evaluations indicated that a highly accurate pharmacogenomic test for SIM would provide a positive incremental net monetary benefit (INMB) for a provincial payer in Canada. However, the value of the test would depend on its ability to accurately diagnose patients when they experience musculoskeletal pain symptoms and guide patients with a test result indicating no SIM to adhere to treatment. Interestingly, our results indicated that a highly inaccurate test would still yield a positive INMB. We found this surprising result was driven by the imbalance of the risk of cardiovascular events outweighing the risk of rhabdomyolysis in patients at high cardiovascular risk. A highly accurate pharmacogenomic test for SIM in patients at high cardiovascular risk would provide economic value for payers. However, the economic and clinical value of the test would depend on the credibility of the test results and their success in influencing patients without SIM to adhere to therapy.

Il existe plusieurs guides ou grilles de lecture critique d’une evaluation economique dans la litterature [78-81]. Tous abordent sensiblement les memes points, c’est pourquoi seule la grille la plus diffusee est reprise ici, avec la permission de l’auteur [82]. Les dix questions proposees par M. F. Drummond pour juger des forces et des faiblesses de la methodologie utilisee dans une evaluation economique sont les suivantes. 1. La question est-elle claire et bien posee ? L’etude considere-t-el...

Statin (HMG-CoA reductase inhibitor) therapy is the mainstay dyslipidemia treatment and reduces the risk of a cardiovascular (CV) event (CVE) by up to 35%. However, adherence to statin therapy is poor. One reason patients discontinue statin therapy is musculoskeletal pain and the associated risk of rhabdomyolysis. Research is ongoing to develop a pharmacogenomics (PGx) test for statin-induced myopathy as an alternative to the current diagnosis method, which relies on creatine kinase levels. The potential economic value of a PGx test for statin-induced myopathy is unknown. We developed a lifetime discrete event simulation (DES) model for patients 65 years of age initiating a statin after a first CVE consisting of either an acute myocardial infarction (AMI) or a stroke. The model evaluates the potential economic value of a hypothetical PGx test for diagnosing statin-induced myopathy. We have assessed the model over the spectrum of test sensitivity and specificity parameters. Our model showed that a strategy with a perfect PGx test had an incremental cost-utility ratio of 4273 Canadian dollars ($Can) per quality-adjusted life year (QALY). The probabilistic sensitivity analysis shows that when the payer willingness-to-pay per QALY reaches $Can12,000, the PGx strategy is favored in 90% of the model simulations. We found that a strategy favoring patients staying on statin therapy is cost effective even if patients maintained on statin are at risk of rhabdomyolysis. Our results are explained by the fact that statins are highly effective in reducing the CV risk in patients at high CV risk, and this benefit largely outweighs the risk of rhabdomyolysis.

Purpose This study aims to develop and evaluate diagnostic algorithms for AIDS, hepatitis C status, alcohol abuse and illicit drug use in the administrative healthcare database of the Province of Quebec, Canada (Regie de l'assurance-maladie du Quebec (RAMQ)). Methods We selected HIV-positive patients contributing to both the RAMQ database and a local clinical database, which was used as gold standard. We developed algorithms to identify the diagnoses of interest in RAMQ using data from hospital discharge summaries and medical and pharmaceutical claims databases. We estimated and compared sensitivity, specificity, positive predictive and negative predictive values and area under receiver operating curve for each algorithm. Results Four hundred twenty patients contributed to both databases. Prevalence of conditions of interest in the clinical database was as follows: AIDS 233 (55%), hepatitis C infection 105 (25%), alcohol abuse 106 (25%), illicit drug use 144 (34%) and intravenous drug use 107 (25%). Sensitivity to detect AIDS, hepatitis C, alcohol abuse, illicit drug use and intravenous drug use was 46% [95%CI: 39–53], 26% [18–35], 50% [37–57], 64% [55–72] and 70% [61–79], respectively. Specificity to detect these conditions was 91% [86–95], 97% [94–98], 92% [88–95], 95% [92–97] and 90% [87–93], respectively. Positive predictive values were 87% [80–92], 71% [54–85], 68% [56–78], 87% [79–93] and 72% [62–80], respectively. Area under receiver operating curve varied from 0.62 [0.57–0.65] for hepatitis C to 0.80 [0.76–0.85] for intravenous drug use. Conclusions Sensitivity was low to detect AIDS, alcohol abuse, illicit drug use and especially hepatitis C in RAMQ. Researchers must be aware of the potential for residual confounding and must consider additional methods to control for confounding. Copyright © 2015 John Wiley & Sons, Ltd.

Over- and undercoagulation with warfarin are associated with hemorrhagic and thromboembolic events, respectively. Genetic and clinical factors affect warfarin response, and the causes of this variability remain unclear. We present descriptive statistics and test for predictors of poor anticoagulation control. The Quebec Warfarin Cohort (QWC) comprises 1059 new warfarin users, with prospective follow-up using telephone questionnaires every 3 months for 1 year, and using healthcare administrative databases (RAMQ and Med-Echo) for 5 years prior to cohort entry and up to 10 years following active patient participation. Genetic material was collected, and genotyping of CYP2C9 and VKORC1 genes was conducted. Measured outcomes included the percentage of time patients spent within therapeutic range, anticoagulation control, warfarin dose, bleeding, and thromboembolic events. We report baseline characteristics and outcomes after 1 year of follow-up. Poor anticoagulation control was defined as time in therapeutic range

Contains fulltext : 174174.pdf (Publisher’s version ) (Open Access) Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values /= 80%) and poor (< 80%) adherence to AHA (P = 0.41) and LLAs (P = 0.11) were similar in the year preceding and the year following the first visit to the renal protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications.

Atrial fibrillation (AF) is common in patients with heart failure. Rhythm- and rate-control strategies are associated with similar efficacy outcomes. We compared the economic impact of the 2 treatment strategies in patients with AF and heart failure from the province of Québec, Canada.In a substudy of the Atrial Fibrillation and Congestive Heart Failure trial, health care expenditures of patients from Québec randomized to rhythm and rate-control treatment strategies were compared from a single-payer perspective using a cost-minimization approach. In-trial resource utilization and unit costs were estimated from Québec Health Insurance Board databases supplemented by disease-specific costs from the Ontario Case Costing Initiative.In all, 304 patients were included, aged 68 ± 9 years; 86% male; ejection fraction, 26% ± 6%. Baseline characteristics were similar in rhythm-control (n = 149) and rate-control (n = 155) groups. Arrhythmia-related costs accounted for 45% of total expenditures. Rate-control patients had fewer cardiac procedures (146 vs. 238, P0.001), driven by fewer cardioversions, and lower costs related to antiarrhythmic drugs (CAD $48 per patient [95% confidence interval {CI}, $21-$96] vs. $1319 per patient [95% CI, $1124-$1522]). However, these differences were offset by higher expenditures due to hospitalizations for noncardiovascular diagnoses, implantable cardiac arrhythmia devices, and noncardiovascular drugs in the rate-control group. The total cost per patient was not significantly different between rhythm-control ($72,764 [95% CI, $61,575-$85,145]) and rate-control ($78,767 [95% CI, $67,101-$92,139]) strategies.In the study population, the therapeutic strategy used to manage AF in patients with severe heart failure appears to have little influence on the overall financial burden, which remains substantial.

We studied the association between HIV infection, antiretroviral medications, and the risk of spontaneous intracranial hemorrhage.We performed a cohort and nested case control study in an administrative database. We selected all HIV-positive individuals presenting between 1985 and 2007. Each HIV-positive subject was matched with 4 HIV-negative individuals. We used a Poisson regression model to calculate rates of intracranial hemorrhage according to HIV status. We conducted a case -control study nested within the cohort of HIV-positive individuals to look at the effect of antiretroviral medications. Odds ratios for antiretroviral exposure were obtained using conditional logistic regression.There were 7,053 HIV-positive and 27,681 HIV-negative subjects, representing 138,704 person-years. There were 49 incident intracranial hemorrhages, 29 in HIV-positive and 20 in HIV-negative individuals. The adjusted hazard ratio for intracranial hemorrhage in HIV-positive compared to HIV-negative patients was 3.28 (95% confidence interval [CI] 1.75-6.12). The effect was reduced to 1.99 (95% CI 0.92-4.31) in the absence of AIDS-defining conditions, and increased to 7.64 (95% CI 3.78-15.43) in subjects with AIDS-defining conditions. Hepatitis C infection, illicit drug or alcohol abuse, intracranial lesions, and coagulopathy were all strongly associated with intracranial hemorrhage (all P.001). In the case control study, 29 cases of ICH in HIV-positive individuals were matched to 228 HIV-positive controls. None of the antiretroviral classes were associated with an increase in the odds ratio of intracranial hemorrhage.The risk of intracranial hemorrhage in HIV-positive individuals seems to be mostly associated with AIDS-defining conditions, other comorbidities, or lifestyle factors. No association was found between use of antiretroviral medications and intracranial hemorrhage.

Background Many observational studies have found an association between the exposure to statins and the increased risk of diabetes, mostly through the use of intent-to-treat (ITT) like exposure measure (EM). ITT like EM may not adequately reflect the mechanism of action by which statins could cause diabetes. Objectives To determine if continuous EMs can more accurately reflect the mechanism of action by which statins and incidence of diabetes would be associated than ITT like EM. Methods We obtained a cohort of 404,129 diabetes-free incident statin users from the Quebec public drug insurance plan. Patients dispensed with a drug used in the treatment of diabetes or diagnosed with diabetes within 2-years follow-up were defined as cases. Controls were randomly matched to each case on the index date. Three EMs were tested. EM 1: exposure to a high versus low dose statin at baseline (ITT like); EM 2: cumulative standardized statin dose (cSSD) at the index date; and EM 3: cSSD in the 180 days prior to the index date. The optimal EM was selected based upon each model's Akaike's information criterion (AIC). Conditional logistic regressions were used to calculate conditional OR and model AIC. Results All three EMs identified an increased risk of diabetes among patients exposed to higher statin doses. Model AIC identified EM 3 as the best EM for this association. Conclusions Our results indicate that higher statin doses increase the risk of diabetes but favour a cumulative reversible diabetogenic effect of statins.

Pharmacogenomics (PGx) tests have the potential of improving the effectiveness of expensive new drugs by predicting the likelihood, for a particular patient, to respond to a treatment. The objective of this study was to develop a pharmacoeconomic model to determine the characteristics and the cost–effectiveness of a hypothetical PGx test, which would identify patients who are most likely to respond to an expensive treatment for chronic heart failure. For this purpose, we chose the example of ivabradine. Our results suggest that the use of a PGx test that could select a subgroup of patients to be treated with an expensive drug has the potential to provide more efficient drug utilization.

The objective of this study was to estimate the maximal clinical benefit that could be reasonably expected from a cholesterol-lowering intervention.We used a hypothetical population at high risk of cardiovascular disease events from three risk assessment models including the Framingham risk function, the Score Canada and the Pooled Cohort Risk Assessment Equations. Our source population were all 55-year-old smoking men with diabetes, hypertension and low HDL. From this population, we identified two different subpopulations named "high" and "low", referring to their cholesterol levels which were set at 8.60 and 4.14 mmol/L respectively. Both subpopulations were identified for each risk assessment model in order to estimate the maximal impact of lowering cholesterol on cardiovascular disease events.Our extrapolations estimated that the maximal theoretical efficacy of a cholesterol-lowering intervention corresponds to a risk ratio ranging between 0.46 and 0.66 over a 10-year period. The number of events prevented during this period were between 21 and 29 per 100 patients which corresponds to a number needed to treat varying from 3.47 to 4.76.Our estimation showed the maximal clinical benefit that could be reasonably expected by an intervention that would lower total cholesterol in high-risk patients.

Background Comparative performance of the traditional propensity score (PS) and high-dimensional propensity score (hdPS) methods in the adjustment for confounding by indication remains unclear. We aimed to identify which method provided the best adjustment for confounding by indication within the context of the risk of diabetes among patients exposed to moderate versus high potency statins. Method A cohort of diabetes-free incident statins users was identified from the Quebec’s publicly funded medico-administrative database (Full Cohort). We created two matched sub-cohorts by matching one patient initiated on a lower potency to one patient initiated on a high potency either on patients’ PS or hdPS. Both methods’ performance were compared by means of the absolute standardized differences (ASDD) regarding relevant characteristics and by means of the obtained measures of association. Results Eight out of the 18 examined characteristics were shown to be unbalanced within the Full Cohort. Although matching on either method achieved balance within all examined characteristic, matching on patients’ hdPS created the most balanced sub-cohort. Measures of associations and confidence intervals obtained within the two matched sub-cohorts overlapped. Conclusion Although ASDD suggest better matching with hdPS than with PS, measures of association were almost identical when adjusted for either method. Use of the hdPS method in adjusting for confounding by indication within future studies should be recommended due to its ability to identify confounding variables which may be unknown to the investigators. Electronic supplementary material The online version of this article (doi:10.1186/s12874-016-0119-1) contains supplementary material, which is available to authorized users.

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia and has been associated with heart failure, stroke, and mortality. The prevalence of AF is expected to rise with the aging population. Our objectives were to characterize the Quebec AF patient population at the time of diagnosis of AF, quantify medical resource use prior to and after the initial diagnosis of AF, and determine overall survival. Methods A retrospective cohort study was undertaken using the Regie de l'Assurance Maladie du Quebec databases to evaluate patients diagnosed with AF between January 1, 1998, and April 30, 2009. Results A total of 64,157 patients were included in our study population. At the time of diagnosis of AF, patients also suffered from several diseases, including heart failure (15.8%) and angina pectoris (15.1%). Compared with the year prior to AF diagnosis, in the year after AF diagnosis patients were more frequently hospitalized (1.5 vs 1.1 hospitalizations) and for longer periods (5.6 vs 3.3 days), and had more outpatient visits (12.9 vs 11.7). Survival rapidly decreased during the first 60 days (60-day mortality, 6.1%) and steadily declined thereafter, with mortality rates of 14.7% and 36.8% at 1 and 5 years, respectively. Conclusion At the time of diagnosis of AF, patients often suffer from several comorbidities. Diagnosis of AF is associated with an increase in medical resource use and higher mortality rates, particularly within the first 60 days.

Antibiotic-associated diarrhea (AAD) and particularly Clostridium difficile-associated diarrhea (CDAD) are the most common causes of healthcare associated infectious diarrhea. A double-blind, dose response, placebo-controlled trial of the probiotic formula (Bio-K+ Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R formula) for prophylaxis of AAD and CDAD was published in 2010. The Bio-K+ Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R formula is a registered trademark of Bio-K Plus International Inc. (Laval, Québec, Canada). Results indicated that the incidence of AAD and CDAD were lower for patients assigned to the probiotic formula compared with the placebo option. The present study aims to estimate the savings in direct medical costs that might result from the use of two different doses of the probiotic formula vs placebo.A cost-consequence analysis was conducted to compare the two doses of the probiotic formula compared to placebo. The analysis was based upon published data and adjusted to the North American context.Economic analyses showed that the use of the probiotic formula would result in estimated mean per patients savings of US$1968 for the single dose and US$2661 for the double dose compared with the placebo option if used an average of 13 days by all patients at risk of developing AAD and CDAD.Several key parameters considered within the economic model were not captured within the Gao et al. study. Numerous sensitivity analyses were conducted to address this issue.The use of the probiotic formula in prophylaxis of AAD and CDAD would lead to estimated savings in direct medical costs that would substantially offset its acquisition cost. Treating 1000 hospitalized patients on antibiotics with the double dose of the product compared to current practice would save a single payer system the sum of $2,661,218.

Background: Morbidity associated with cardiovascular disease is increasing in the HIV-infected population. We aimed to study the impact of HIV and of antiretrovirals on acute myocardial infarction (AMI). Methods: We performed a cohort and a nested case-control study using the dataset of the Regie de l'Assurance Maladie du Quebec. HIV-positive patients were identified using ICD-9 diagnostic codes and matched to HIV-negative patients. Within the HIV-positive cohort, cases of AMI were identified and matched to HIV-positive patients without AMI. The coprimary outcomes were the risk of AMI associated with HIV exposure in the cohort study and that associated with exposure to antiretrovirals in the case-control study. Data were analysed using Poisson and conditional logistic regression. Results: About 7053 HIV-positive patients were matched to 27,681 HIV-negative patients. Incidence rates of AMI in the HIV+ cohort was 3.88 95% confidence interval (CI) (3.26 to 4.58) per 1000 patient-years, compared to 2.21 95% CI (1.93 to 2.52) per 1000 patient-years in the HIV cohort. The adjusted incidence ratio of AMI for HIV-infected patients was 2.11 95%CI (1.69 to 2.63). Among HIV+ patients, 125 AMI cases were matched with 1084 HIV+ patients. We found increased odds ratio (95% CI) of AMI associated with any exposure to abacavir 1.79 (1.16 to 2.76), P = 0.02, efavirenz 1.83 (1.21 to 2.76) P = 0.004, lopinavir 1.98 (1.24 to 3.16) P = 0.004, and ritonavir 2.29 (1.48 to 3.54) P < 0.001. Conclusions: HIV+ individuals were at higher risk of AMI than the general population, and several antiretrovirals were associated with an increased risk of AMI. Results should be interpreted with caution in absence of data on smoking and HIV clinical status.

Despite being effective in the primary and secondary prevention of sudden cardiac arrest, the cost-effectiveness of implantable cardioverter-defibrillator (ICD) therapy remains debated. We attempted to estimate the value ICD recipients place on their ICD device. We used the contingent valuation method to evaluate the willingness to pay (WTP) and the cost benefit of ICD therapy in an unselected population of 237 recipients. A hypothetical scenario was presented to patients in which at the end of their current ICD no public reimbursement for the replacement would occur. Patients were asked to indicate their out-of-pocket WTP for a replacement ICD using a close-ended question format. Seven different "take-it-or-leave-it" bids were randomly varied and assigned to patients. Median WTP was calculated with nonparametric methods, and multiple logistic regression models were generated to identify factors associated with WTP. Only cost of the device was considered. Median WTP was estimated at CAN $4,125, which corresponds to 21% of the cost of the device (CAN $20,000). In multiple logistic regression analysis, a higher bid (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.91 to 0.99, per CAN $1,000 increase) was associated with a lower WTP, whereas a higher gross family income (OR 2.3, 95% CI 0.9 to 9.0) and higher education (OR 2.2, 95% CI 0.9 to 5.1) were associated with a trend for higher WTP. In conclusion, ICD recipients would be willing to pay a substantial amount for a replacement ICD. Considering the expensive price of the device, ICD recipients value favorably the benefits provided by the ICD.

Background— Percutaneous coronary intervention (PCI) remains limited by the risk of restenosis. Patients' perceptions of the health benefits and value of avoiding restenosis are incompletely known. Methods and Results— We used a contingent valuation approach to assess the willingness to pay (WTP) for a hypothetical treatment that eliminates the risk of restenosis among 270 PCI patients. Patients were provided with a scenario describing a baseline 10% or 20% probability of restenosis in the year following the procedure, which could lead to repeat PCI or, more rarely, bypass surgery, without any increase in mortality. Six different “take it or leave it” bids ($500, $1000, $1500, $2000, $2500, and $3000) and both risk levels were randomly assigned. Multiple logistic regression was used to identify independent predictors of a positive response to the WTP question. Using nonparametric methods, the median WTP to eliminate the risk of restenosis was estimated at $2802. As expected, higher income was independently associated with a higher probability of a positive response to the WTP question (odds ratio, 2.81; 95% CI, 1.32 to 5.97). Bids also were independently associated with the probability of being willing to pay, and this association followed a quadratic effect. Below $1500, bid had little impact on patient answers. However, as prices increased, the probability of being willing to pay started to decrease sharply. Conclusion— The potential to eliminate the risk of restenosis, a benign complication, would have substantial value for patients undergoing PCI.

Dizziness is known to be associated with the risk of falls. However, there is not much evidence for the increase of fractures caused by dizziness.The aim of the study was to investigate whether the symptom of dizziness is associated with an increased fracture rate.We performed a retrospective cohort study using a population-based administrative database in the Province of Quebec, Canada. A cohort of n = 2442 patients with at least one diagnosis of dizziness was compared to n = 16,125 unexposed patients. The main outcome measure was any kind of first fracture after the index date of dizziness.Analysis revealed a moderate effect of dizziness as an independent contributing factor to fractures (adjusted hazard ratio (HR) 1.26, 95% confidence interval 1.03 to 1.55). A fracture in the year before the index date was highly associated with the incidence of a subsequent fracture (HR 2.69, 2.09 to 3.47), and fractures were less frequent in women (HR 0.70, 0.60-0.82). Analysis further revealed that dizziness (HR 1.31, 1.05-1.64) and prior fractures (HR 2.41, 1.81-3.22) were associated with non-osteoporotic fractures, which were also less frequent in women (HR 0.59, 0.50-0.71). The incidence of fractures in sites typical for osteoporosis correlated with a precedent fracture (HR 3.91, 2.31-6.63), but not with dizziness (HR 1.10, 0.69-1.75).Besides the 'typical' elderly female patient being at risk of osteoporotic fractures, male patients suffering from dizziness should be carefully evaluated, and prevention strategies should be considered to minimise their risk of suffering non-osteoporotic fractures.

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individual's risk profile for fractures.

PurposeThe purpose of this paper is to docoment a randomized controlled trial, with follow‐up at three and six months, to determine the impact of a coronary risk factor modification program for employees.Design/methodology/approachIntervention participants received a 12‐week health promotion program involving exercise, education seminars, nutritional analysis and smoking cessation counselling. Outcome measures included differences in coronary risk factors of control and intervention participants between baseline and three and six‐month follow‐up visits.FindingsThe participants included 566 individuals employed in the Halifax area, Nova Scotia, Canada. They were between 19 and 66 years old with at least two modifiable coronary risk factors. There were statistically significant differences at three months in coronary risk score improvement, smoking cessation, physical activity level increases, body mass index reductions and serum cholesterol. At six months, improvements remained significant except for cholesterol. Reduction in blood pressure was not significantly different. Intervention participants compared to control participants showed significant differences in both cardiac and stroke risk at three and six‐month visits.Practical implicationsThis study demonstrates that employees had a significant coronary disease risk reduction as a result of a relatively short health promotion intervention. Benefits three months post‐intervention were not sustained to the same extent as during the intervention. This underscores the need for long‐term commitment with lifestyle changes and raises the issue of the need for a comprehensive approach that also addresses environmental factors.Originality/valueThis paper contributes to the current research base on this topic as there are few well‐designed studies to reduce coronary risk factors for employees.

Public drug programs in Canada are increasingly implementing cost management strategies. A multidisciplinary review of these strategies—specifically, the special authorization (SA) process—found that implementation of the SA practice is costly and causes inequity in access, underutilization, and delays in treatment for urgently required therapies, all potentially leading to negative health outcomes. We present potential solutions and a set of recommendations for decision-makers to base reimbursement decisions on the best clinical evidence, eliminate regional variability in access, ensure timely access to urgently required treatments, and monitor the impact of reimbursement policies on health outcomes.

OBJECTIVE: To determine whether isotretinoin increases the risk of depression in patients with acne vulgaris. METHOD: A case-crossover study was performed among subjects who received > or = 1 isotretinoin prescription from 1984 through 2003. Data were obtained from the Regie de l'Assurance Maladie du Quebec (RAMQ) and Quebec's hospital discharge (Med-Echo) administrative databases. Cases were defined as those with a first diagnosis or hospitalization for depression (ICD-9 codes: 296.2, 298.0, 300.4, 309.0, 309.1, and 311) during the study period (1984-2003) and those who filled a prescription for an antidepressant in the 30 days following their diagnosis or hospitalization. The index date was the calendar date of the diagnosis or hospitalization for depression. Cases were covered by the RAMQ drug plan and had > or = 1 acne diagnosis in the 12 months prior to the index date. Those who received an antidepressant in 12 months prior to the index date were excluded. Exposure to isotretinoin in a 5-month risk period immediately prior to the index date was compared to a 5-month control period. Relative risks along with 95% CIs were estimated using conditional logistic regression. RESULTS: Of the 30,496 subjects in the initial cohort, 126 (0.4%) cases met inclusion criteria. The crude relative risk for those exposed to isotretinoin was 2.00 (95% CI = 1.03 to 3.89). After adjusting for potential time-dependent confounders, the relative risk for those exposed to isotretinoin was 2.68 (95% CI = 1.10 to 6.48). CONCLUSION: This is the first controlled study to find a statistically significant association between isotretinoin and depression. Because depression could have serious consequences, close monitoring of isotretinoin users is indicated. Language: en

Background: In Canada, access to clopidogrel is restricted by most provincial drug insurance plans in order to contain costs. Until April 2007, the Regie de l9assurance maladie du Quebec (RAMQ) Prescription Drug Insurance Plan reviewed special access forms before approving reimbursement for clopidogrel prescriptions. We investigated the impact of this restrictive process on patient9s filling of prescriptions and on all-cause mortality following coronary stenting. Methods: We analyzed prescriptions filled and all-cause mortality in the year following a percutaneous coronary intervention among patients who underwent stent implantation between January 2000 and September 2004. We obtained administrative data from the RAMQ databases. We included patients who filled at least 1 prescription for a nonrestricted cardiovascular drug after hospital discharge. We used Cox proportional models to compare mortality rates as a function of delayed or absent outpatient clopidogrel therapy. Results: Of 13 663 patients, 1571 (11.5%) did not fill any clopidogrel prescription despite filling at least 1 nonrestricted cardiovascular drug prescription after a percutaneous coronary intervention, and 1174 (8.6%) patients filled their clopidogrel prescription with a delay of at least 1 day (median delay 5 days) after filling the nonrestricted cardiovascular drug prescription. After controlling for pertinent covariables, not filling a clopidogrel prescription (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.35–2.15) and filling with a delay (HR 1.34, 95% CI 1.01–1.80) were associated with a significant increase in all-cause mortality. Interpretation: Restricted access to clopidogrel was associated with about 20% of patients either not receiving clopidogrel or receiving therapy after a delay. Delay or absence of clopidogrel therapy increased the risk of all-cause mortality after percutaneous coronary intervention with stenting.