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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.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Aims: In the randomized, placebo-controlled Colchicine Cardiovascular Outcomes Trial (COLCOT) of 4745 patients enrolled within 30 days after myocardial infarction (MI), low-dose colchicine (0.5 mg once daily) reduced the incidence of the primary composite endpoint of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. To assess the in-trial period and lifetime cost-effectiveness of low-dose colchicine therapy compared to placebo in post-MI patients on standard-of-care therapy. Methods and results: A multistate Markov model was developed incorporating the primary efficacy and safety results from COLCOT, as well as healthcare costs and utilities from the Canadian healthcare system perspective. All components of the primary outcome, non-cardiovascular deaths, and pneumonia were included as health states in the model as both primary and recurrent events. In the main analysis, a deterministic approach was used to estimate the incremental cost-effectiveness ratio (ICER) for the trial period (24 months) and lifetime (20 years). Over the in-trial period, the addition of colchicine to post-MI standard-of-care treatment decreased the mean overall per-patient costs by 47%, from $502 to $265 Canadian dollar (CAD), and increased the quality-adjusted life years (QALYs) from 1.30 to 1.34. The lifetime per-patient costs were further reduced (69%) and QALYs increased with colchicine therapy (from 8.82 to 11.68). As a result, both in-trial and lifetime ICERs indicated colchicine therapy was a dominant strategy. Conclusion: Cost-effectiveness analyses indicate that the addition of colchicine to standard-of-care therapy after MI is economically dominant and therefore generates cost savings.

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.

Background Statins are the mainstay hypercholesterolemia treatment and reduce the risk of cardiovascular events in patients. However, statin therapy is often interrupted in patients experiencing musculoskeletal pain or myopathy, which are common in this patient group. Currently, the standard tests for diagnosing statin myopathies are difficult to interpret. A pharmacogenomics (PGx) test to diagnose statin-induced myopathy would be highly desirable. Methods We developed a Markov state model to assess the cost-effectiveness of a hypothetical PGx test, which aims to identify statin-induced myopathy in high-risk, secondary prevention cardiovascular patients. The alternative strategy hypothesized is that physicians or patients interrupt the statin therapy in the presence of musculoskeletal pain. Our model includes health states specific to the PGx test outcome which assesses the impact of test errors. Results Assuming a perfect test, the results indicate that the PGx test strategy dominates when the test costs less than CAN$356, when the strategy is cost neutral. These results are robust to deterministic and probabilistic sensitivity analyses. Conclusion Our base-case results show that a PGx test for statin-induced myopathy in a high-risk, secondary prevention of a cardiovascular event population would be a dominant solution for a test cost of CAN$356 or less. Furthermore, the modelling of the complete range of diagnostic test outcomes provide a broader understanding of the economic value of the pharmacogenomics test.

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...

La pharmacoéconomie est devenue un domaine incontournable dans le monde de la santé. À lui seul, le poids des contraintes budgétaires justifie son développement constant. Elle constitue un outil indispensable pour de nombreux acteurs au sein de l’industrie pharmaceutique, du milieu médical et des pouvoirs publics. Ces intervenants y ont recours en tant qu’investigateurs mais surtout en tant qu’utilisateurs d’évaluations pharmacoéconomiques. Cet ouvrage s’adresse à toute personne désireuse de connaître les rudiments de la pharmacoéconomie. En présentant les principes de base de façon simple et claire, il vise à permettre aux étudiants et aux professionnels de comprendre les résultats d’une évaluation pharmacoéconomique et de pouvoir juger de sa qualité afin d’en faire une juste interprétation.

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.

Pre-exposure prophylaxis for individuals who are at high risk for HIV infection has been shown to be effective at preventing infection. The authors of this article aimed to investigate whether ‘on-demand’ pre-exposure prophylaxis is also cost effective, specifically in Canada in a population of men who have sex with men, who are at higher risk for HIV infection. The authors used multiple methods to generate a thorough cost-effectiveness analysis that has implications for the use of this therapy in Canada., BACKGROUND: Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of HIV infection. The cost effectiveness of ‘on demand’ PrEP for non-injection drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated. OBJECTIVE: To conduct an economic evaluation of the societal costs of HIV in Canada and evaluate the potential benefits of this PrEP strategy. METHODS: Direct HIV costs comprised outpatient, inpatient and emergency department costs, psychosocial costs and antiretroviral costs. Resource consumption estimates were derived from the Centre Hospitalier de l’Université de Montréal HIV cohort. Estimates of indirect costs included employment rate and work absenteeism. Costs for ‘on demand’ PrEP were modelled after an ongoing clinical trial. Cost-effectiveness analysis compared costs of ‘on demand’ PrEP to prevent one infection with lifetime costs of one HIV infection. Benefits were presented in terms of life-years and quality-adjusted life-years. RESULTS: The average annual direct cost of one HIV infection was $16,109 in the least expensive antiretroviral regimen scenario and $24,056 in the most expensive scenario. The total indirect cost was $11,550 per year. Total costs for the first year of HIV infection ranged from $27,410 to $35,358. Undiscounted lifetime costs ranged from $1,439,984 ($662,295 discounted at 3% and $448,901 at 5%) to $1,482,502 ($690,075 at 3% and $485,806 at 5%). The annual cost of PrEP was $12,001 per participant, and $621,390 per infection prevented. The PrEP strategy was cost-saving in all scenarios for undiscounted and 3% discounting rates. At 5% discounting rates, the strategy is largely cost-effective: according to least and most expensive scenarios, incremental cost-effectiveness ratios ranged from $60,311 to $47,407 per quality-adjusted life-year. CONCLUSION: This ‘on demand’ PrEP strategy ranges from cost-saving to largely cost-effective. The authors believe it represents an important public health strategy for the prevention of HIV transmission.

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.