Lyne Nadeau

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data

Objective To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs). Design Systematic review followed by a one stage bayesian individual patient data meta-analysis. Data sources Studies from Canadian and European healthcare databases. Review methods Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. Exposure and outcomes Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction. Results A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations. Conclusions All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.

The evolution of stroke in Quebec A 15-year perspective

Objective: To estimate changes in rates of cerebral infarction and intracerebral hemorrhage, comorbidity profile, and case fatality rates in Quebec over 15 years. Methods: A population-based admission-to-discharge cohort study was conducted, selecting first stroke events from hospital discharge data (MedEcho) from 1988 to 2002. Results: In this study (involving 101,831 persons with cerebral infarctions and 11,215 persons with intracerebral hemorrhages), there was a downturn in the rates of cerebral infarction over 15 years, especially during the last 5 years (32.5% decline for men and 25.5% for women). A concomitant increase in rates of intracerebral hemorrhage, 28% increase for men (2%/year) and 22% for women (1.6%/year), was also noted. Although age and comorbidity of the population increased, case fatality decreased over time. Age and type of stroke were strong predictors for early (≤7 days) and later (8 to 30 days) case fatality, whereas comorbidity was important only for later death. In-hospital bed stay declined dramatically over time for all discharge destinations. Conclusions: A significant decrease in rates of cerebral infarction and a rise in rates of intracerebral hemorrhage were noted in Quebec over 15 years. Age and comorbidity of the population increased. Although stroke is increasingly a condition of the elderly, ill population, case fatality and in-hospital bed stay declined over time.

Does the addition of functional status indicators to case-mix adjustment indices improve prediction of hospitalization, institutionalization, and death in the elderly?

Background:Case-mix adjustment is widely used in health services research to ensure that groups being compared are equivalent on variables predicting outcome. There has been considerable development and testing of comorbidity indices derived from diagnostic codes recorded in administrative databases, but increasingly, the benefit of clinical information and patient reported ratings of health and functional status is being recognized. One type of information that is highly valued but has so far not been captured by administrative health databases is functional status indicators (FSI). Objective:The purpose of this study was to estimate the extent to which prediction of health outcomes can be improved on by including information on functional status indicators (FSI). Research Design:The data for the current study was obtained from a clustered randomized trial evaluating computerized decision support for managing drug therapy in the elderly, conducted from 1997 to 1998. A total of 107 primary care physicians participated in this trial and 6465 of their patients (51%) completed a generic health status measure—the SF-12—before the intervention. C statistics and R2 were used to compare the predictive value of sociodemographic factors, 2 comorbidity indices, and 11 FSI predictor variables derived from the SF-12 and coded (possible for 8) using the International Classification of Functioning (ICF). Results:Using stepwise logistic regression, FSI, particularly limitation in stair climbing or doing moderate activities like housework, were found to be strong and independent predictors of all outcomes, even after controlling for sociodemographics and comorbidity. Conclusion:This study indicates that FSI provided as robust a prediction of health events as did complex comorbidity indices. Additionally, the ICF coding system provides a mechanism whereby information on FSI could be incorporated into administrative databases through the use of electronic health records that include a health or functional status measure.

The effect of obesity on antibiotic treatment failure: a historical cohort study.

Obesity, a major health issue, is also an important risk factor for infections. Evidence demonstrates that excess weight affects the disposition of antibiotics but little work has been done to explore if this results in antibiotic treatment failure (ATF). ATF has serious adverse health outcomes and may increase treatment resistance. Given that obese patients often have other health issues, it is important to determine if excess weight independently increases the likelihood of ATF.

Effect of Oral Bisphosphonates for Osteoporosis on Development of Skeletal Metastases in Women With Breast Cancer: Results From a Pharmaco-Epidemiological Study

BACKGROUND Treatment with bisphosphonates in women with breast cancer and established bone metastasis delays further skeletal-related events. Evidence is emerging that bisphosphonates are beneficial for secondary prevention of bone metastasis. The study aimed to estimate the effect of oral bisphosphonates for treatment or prevention of osteoporosis on development of bone metastasis in a population of women with breast cancer. METHODS A historical cohort of 21664 women diagnosed with breast cancer was created from health administrative data in Quebec, Canada. The primary outcome was time to develop bone metastasis; exposure was bisphosphonate use prediagnosis, postdiagnosis, both, or neither and a cumulative index of drug exposure. The sample was stratified according to stage (0-II or III) at time of diagnosis. Cox proportional hazards tested the effect of bisphosphonate use on time to develop bone metastases. RESULTS Taking bisphosphonates postdiagnosis of breast cancer only or continuing bisphosphonates started prior to diagnosis after diagnosis was associated with a reduction in risk of bone metastasis from 45% to 28% in women with local disease at diagnosis. In women with regional disease, postdiagnosis bisphosphonate use, with or without prediagnosis use, reduced risk by almost 50%. A statistically significant dose-response trend was observed relating increased use to lower risk (slope = 0.94, 95% confidence interval = 0.90 to 0.99). Bisphosphonates were also associated with a decreased risk of all-cause mortality similar to that of the development of bone metastasis. CONCLUSION Low-dose oral bisphosphonates administered for prevention or treatment of postmenopausal osteoporosis were associated with lower risk of skeletal metastasis in patients with early- or more advanced-stage breast cancer.

MyRisk_Stroke Calculator: A Personalized Stroke Risk Assessment Tool for the General Population

Background and Purpose There is a variety of stroke risk factors, and engaging individuals in reducing their own personal risk is hugely relevant and could be an optimal dissemination strategy. The aim of the present study was to estimate the stroke risk for specific combinations of health- and lifestyle-related factors, and to develop a personalized stroke-risk assessment tool for health professionals and the general population (called the MyRisk_Stroke Calculator). Methods This population-based, longitudinal study followed a historical cohort formed from the 1992 or 1998 Santé Québec Health Surveys with information for linkage to health administrative databases. Stroke risk factors were ascertained at the time of survey, and stroke was determined from hospitalizations and death records. Cox proportional hazards models were used, modeling time to stroke in relationship to all variables. Results A total of 358 strokes occurred among a cohort of 17805 persons (men=8181) who were followed for approximately 11 years (i.e., -200000 person-years). The following regression parameters were used to produce 10-year stroke-risk estimates and assign risk points: for age (1 point/year after age 20 years), male sex (3 points), low education (4 points), renal disease (8 points), diabetes (7 points), congestive heart failure (5 points), peripheral arterial disease (2 points), high blood pressure (2 points), ischemic heart disease (1 point), smoking (8 points), >7 alcoholic drinks per week (3 points), low physical activity (2 points), and indicators of anger (4 points), depression (4 points), and anxiety (3 points). According to MyRisk_Stroke Calculator, a person with <50, 75, and 90 risk points has a 10-year stroke risk of <3%, 28%, and >75%, respectively. Conclusions The MyRisk_Stroke Calculator is a simple method of disseminating information to the general population about their stroke risk.

Improving post-stroke health outcomes: Can facilitated care help?

OBJECTIVES The objectives of this study were (1) identifying the patterns of post-stroke care, (2) determining the care-provider and patient characteristics associated with optimal management of post-stroke care and (3) estimating the potential influence of various facilitated care policies on outcomes. METHODOLOGY The 3946 subjects included in the study were admitted to one of Quebecs acute-care hospitals with confirmed diagnosis of stroke and subsequently discharged to their home. The records related to fee-for-service billings of this sample were obtained for the 3 months following discharge and used to define the care-provider path for each stroke survivor. These paths were analyzed and the potential impact of various facilitated care interventions was estimated via a Markov model. RESULTS The rate of mortality for this sample was 3.2% during the first 3 months after discharge. For the patients who were re-hospitalized, however, the mortality rates were up to 10.3% depending on the care-provider visited prior to re-hospitalization. Our analyses indicate that by avoiding such critical sub-paths via facilitated care, it is possible to achieve improvements in health outcomes as well as cost. DISCUSSION There is a window of opportunity for improving community-based post-stroke care. Facilitated care policies concerning planned visits upon discharge from hospital or following ER visits can improve the outcomes.

Risk of acute myocardial infarction with real-world NSAIDs depends on dose and timing of exposure

Real‐life use of nonsteroidal anti‐inflammatory drugs (NSAIDs) is dynamic. This study aimed to characterize the temporal association between time‐varying NSAID exposure and acute myocardial infarction (MI).

Studying additive interaction in a healthcare database: Case study of NSAIDs, cardiovascular profiles, and acute myocardial infarction

Purpose There are clinical trial data on risk of acute myocardial infarction (MI) with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at increased cardiovascular (CV) risk requiring chronic daily treatment. This study investigated whether risks of acute MI with real-world prescription NSAIDs, such as low-dose or intermittent use, vary according to an individual’s CV profile. Methods Nested case-control analyses were carried out on an administrative health cohort from Quebec, Canada by randomly selecting 10 controls per case matched on age ± 1 year, sex, and month and year of cohort entry. We measured the additive joint effects on acute MI of current NSAID use and presence of hypertension, coronary heart disease (CHD), history of previous MI, or concomitant use of cardioprotective aspirin. The endpoint was the relative excess risk due to interaction (RERI). To verify the robustness of interaction findings, we performed sensitivity analyses with varying specifications of NSAID exposure-related variables. Results The cohort consisted of 233 816 elderly individuals, including 21 256 acute MI cases. For hypertension, CHD, and previous MI, we identified additive interactions on MI risk with some but not all NSAIDs, which also depended on the definition of NSAID exposure. Hypertension was sub-additive with naproxen but not with the other NSAIDs. Celecoxib and CHD were sub-additive in the primary analysis only (modelling NSAID dose on index date or up to 7 days before–best-fitting base model) whereas celecoxib and rofecoxib were super-additive with a history of previous MI in the secondary analysis only (modelling NSAID use on index date). For cardioprotective aspirin we found no evidence for an additive interaction with any of the NSAIDs. Conclusions Alternative specifications of NSAID exposure concurred in finding that concomitant use of cardioprotective aspirin does not attenuate the risks of acute MI with NSAIDs. However we were unable to demonstrate consistent interactions between an individual’s cardiovascular comorbidities and NSAID-associated acute MI. Our study highlights challenges of studying additive interactions in a healthcare database and underscores the need for sensitivity analyses.