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Biomedical subjects

Samy Suissa

Publications and source records attributed to Samy Suissa.

At least 19 recordsLinked to original sources
PubMed2005

Estrogen therapy and risk of cognitive decline: results from the Women's Estrogen for Stroke Trial (WEST).

OBJECTIVE: This study was undertaken to assess whether estrogen therapy (ET) reduces the risk of cognitive decline in women with cerebrovascular disease. STUDY DESIGN: We conducted a randomized, double-blind trial of estradiol 17beta versus placebo for secondary stroke prevention in 664 postmenopausal women with a recent stroke or transient ischemic attack. The Mini-Mental State Examination (MMSE) and 5 domain measures were obtained at baseline and exit. RESULTS: Among 461 women withdrawn alive without stroke, ET did not have a significant effect on cognitive measures after an average of 3 years (relative risk of MMSE decline: 0.74, 95% CI, 0.49-1.13). In women with normal MMSE at entry, estrogen was associated with less decline (relative risk, 0.46, 95% CI, 0.24-0.87). CONCLUSION: In this study, estradiol did not have significant effects on cognitive measures. However, in women with normal function at baseline, there may be a benefit for ET in reducing the risk for cognitive decline.

Aged↗
PubMed2005

Short-acting inhaled beta-2-agonists increased the mortality from chronic obstructive pulmonary disease in observational designs.

OBJECTIVE: The effect of short-acting inhaled beta(2)-agonists on mortality from chronic obstructive pulmonary disease (COPD) is controversial. Different observational designs were used to investigate about this topic. STUDY DESIGN AND SETTING: A population-based case-control design was performed, by linking automated health databases from the Varese Province of Italy. Deaths of COPD generated from the cohort of 135,871 patients for whom at least one prescription for drugs used to treat COPD had been dispensed between 1997 and 1999 entered into the study as cases. Up to 20 controls were randomly selected for each case from the cohort after matching on gender, age, and date of cohort entry. Risk ratios were estimated using the case-control, case-crossover, and case-time-control approaches. RESULTS: A total of 222 cases and 3022 controls met the inclusion criteria. Odds ratios (and corresponding 95% confidence intervals) corresponding to more than 0.5 defined-daily-doses were 2.6 (1.7, 4.0), 1.9 (1.1, 3.3), 2.1 (1.1, 4.0), and 2.3 (1.2, 4.6) by using crude and adjusted case-control, case-crossover, and case-time-control estimates, respectively. CONCLUSION: Evidence that higher doses of short-acting inhaled beta(2)-agonists are associated with higher mortality from COPD was consistently supplied by three observational approaches.

Adrenergic beta-Agonists↗
PubMed2005

The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin System Study.

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.

Adult↗
PubMed2004

MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood.

The prognostic factors for relapse of the initial MRI findings after a first episode of acute CNS inflammatory demyelination are unclear in children. In this study we aimed to identify initial MRI factors that are predictive of a second attack and disability after a first episode of acute CNS inflammatory demyelination in childhood. A cohort of 116 children who had a first episode of acute CNS inflammatory demyelination between 1990 and 2002 was studied using survival analysis methods. The initial MRI data were reviewed in a systematic, standardized, double-blind manner. The average follow-up was 4.9 +/- 3 years. Multivariate analysis showed that the rate of second attack was higher in patients with corpus callosum long axis perpendicular lesions (34 out of 116 patients, 30%) on the initial MRI [hazard ratio (HR) 2.89; 95% confidence interval (CI) 1.65-5.06] and/or with the sole presence of well-defined lesions (46 out of 116 patients, 40%) (HR 1.71; 95% CI 1.29-2.27). Both criteria were more specific predictors (100%) of relapse, demonstrating conversion to multiple sclerosis, than the three Barkhof criteria (63%), but were less sensitive (21% compared with 52%). None of the MRI criteria was predictive of severe disability. Using initial MRI and survival analysis methods, we identified two specific predictors of relapse and conversion to multiple sclerosis after a first episode of acute CNS inflammatory demyelination in childhood. Their low sensitivity, however, shows that this prediction remains difficult.

Acute Disease↗
PubMed2004

Newer disease-modifying antirheumatic drugs and the risk of serious hepatic adverse events in patients with rheumatoid arthritis.

BACKGROUND: Spontaneous cases of hepatic adverse events have been reported in patients with rheumatoid arthritis who were being treated with leflunomide, one of the newer disease-modifying antirheumatic drugs (DMARDs). We assessed the risk of hepatic events associated with the use of leflunomide and other DMARDs. METHODS: Two cohorts comprising 41,885 patients with rheumatoid arthritis who had been dispensed a DMARD between September 1, 1998, and December 31, 2001, were formed using claims databases. Follow-up was from the first dispensing date to the occurrence of a serious or nonserious hepatic event. A nested case-control approach was used to estimate adjusted rate ratios of hepatic events associated with DMARDs dispensed during the prior year, as compared with methotrexate monotherapy. RESULTS: There were 25 cases of serious hepatic events (rate, 4.9 per 10,000 per year) and 411 nonserious hepatic events (rate, 80.0 per 10,000 per year). There was no increase in the rate of serious hepatic events with either leflunomide (rate ratio [RR] = 0.9; 95% confidence interval [CI]: 0.2 to 4.9) or traditional DMARDs (RR = 2.3; 95% CI: 0.8 to 6.5). However, the rate was increased with biologic DMARDs (RR = 5.5; 95% CI: 1.2 to 24.6). The rate of nonserious hepatic events was also increased with biologic DMARDs (RR = 1.5; 95% CI: 1.0 to 2.3), but not with leflunomide (RR = 0.9; 95% CI: 0.7 to 1.3) and traditional DMARDs (RR = 1.1; 95% CI: 0.8 to 1.4). CONCLUSIONS: We found no evidence of an excess risk of serious or nonserious hepatic events with the use of leflunomide as compared with methotrexate. Still, the increased risk observed with the new biologic DMARDs should be investigated further.

Adult↗
PubMed2004

Variability of breast cancer risk in observational studies of hormone replacement therapy: a meta-regression analysis.

OBJECTIVES: A re-analysis of data from 51 epidemiological studies reported a significant 14% increase in the risk of breast cancer associated with the use of hormone replacement therapy (HRT). Unlike randomized trials, these observational studies varied in design and methods. This study was conducted to explore the impact of study design factors on the rate ratio. METHODS: We performed a meta-regression analysis of 39 epidemiological studies of HRT and breast cancer. The rate ratio of breast cancer associated with ever use of HRT was evaluated in relation to study design, study period, country, primary study objective, method of exposure measurement, age control, adjustment factors related to reproduction and menopause, and the presence of breast cancer surveillance. We used stepwise multiple regression analysis, weighted by the inverse of the variance of the logarithm of the rate ratio, to estimate ratios of rate ratios for these factors. RESULTS: Exposure measured by personal interview and/or medical record review was associated with a 14% lower rate ratio estimate as compared with telephone interview or self-administered questionnaire (P = 0.018). Among studies that did not adjust for age at menopause, the rate ratio was 12% lower if the primary objective was HRT effect than not (P = 0.016), while it was 43% higher among studies that adjusted for age at menopause (P = 0.042). An index that included as six desirable design features, breast cancer surveillance, matching of controls, more reliable exposure information, adjustment for age at menopause and reproductive risk factors, and as primary objective the effect of HRT suggests that studies with none of these properties would lead to a rate ratio estimate of 1.14 (95% CI: 1.00-1.29) while studies with all six properties would produce a rate ratio of 0.98 (95% CI: 0.83-1.15). CONCLUSIONS: Design factors of epidemiological studies could be an alternative explanation for the reported 14% increase in the risk of breast cancer associated with the use of HRT.

Breast Neoplasms↗
PubMed2004

First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability.

OBJECTIVES: To evaluate prognostic factors for second attack and for disability in children presenting with an initial episode of central nervous system (CNS) demyelination. STUDY DESIGN: A cohort of 296 children having a first episode of acute CNS inflammatory demyelination was studied by survival analysis. RESULTS: The average follow-up was 2.9+/-3 years. At the end of the follow-up, 57% of patients had a diagnosis of multiple sclerosis (MS), 29% had a monophasic acute disseminated encephalomyelitis, and 14% had a single focal episode. The rate of a second attack was (1). higher in patients with age at onset >or=10 years (hazard ratio, 1.67; 95% CI, 1.04-2.67), MS-suggestive initial MRI (1.54; 1.02-2.33), or optic nerve lesion (2.59; 1.27-5.29); and (2). lower in patients with myelitis (0.23; 0.10-0.56) or mental status change (0.59; 0.33-1.07). Of patients with a second attack, 29% had an initial diagnosis of acute disseminated encephalomyelitis. At the end of the follow-up period, 90% of patients had no or minor disability. Occurrence of severe disability was associated with a polysymptomatic onset (3.25; 1.16-11.01), sequelae after the first attack (26.65; 9.42-75.35), further relapses (1.49; 1.16-1.92), and progressive MS (3.57; 1.21-8.72). CONCLUSIONS: Risk of second attack of CNS demyelination is higher in older patients and lower in patients with mental status change. Risk of disability is higher in polysymptomatic and relapsing patients.

Acute Disease↗
PubMed2004

The utility of the Health Plan Employer Data and Information Set (HEDIS) asthma measure to predict asthma-related outcomes.

BACKGROUND: The Health Plan Employer Data and Information Set (HEDIS) measures are used extensively to measure quality of care. OBJECTIVE: To evaluate selected aspects of the HEDIS measure of appropriate use of asthma medications. METHODS: Claims data were analyzed for commercial health plan members who met HEDIS criteria for persistent asthma in 1999. The use of asthma medications was evaluated in the subsequent year with stratification by controller medication and a measure of adherence (days' supply). Multivariate logistic regressions were used to evaluate the association among long-term controller therapy for persistent asthma, adherence to therapy, and asthma-related hospitalizations or emergency department (ED) visits, controlling for demographic, preindex utilization, and other confounding characteristics. RESULTS: Of the 49,637 persistent asthma patients, approximately 35.7% were using 1 class of long-term controller medications, 18.4% were using more than 1 class, and 45.9% were not using such medication. More than 25% of the persistent asthma patients did not use any asthma medication in the subsequent year. Patients with low adherence to controller medication had a significantly higher risk (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.42-2.08) of ED visit or hospitalization relative to patients not using any controllers compared with persons with moderate (OR, 0.84; 95% CI, 0.57-1.23) or high (OR, 0.70; 95% CI, 0.34-1.44) adherence. Patients receiving a high days' supply of inhaled corticosteroids had the lowest risk of ED visit or hospitalization (OR, 0.37; 95% CI, 0.05-2.69). CONCLUSIONS: Our findings suggest that refinements to the HEDIS measure method for identifying patients with persistent asthma may be needed.

Adult↗
PubMed2003

Inhaled and nasal corticosteroid use and the risk of fracture.

Studies of the risk of fracture associated with inhaled corticosteroids are inconclusive and are limited to short-term effects. We assessed whether long-term use increases this risk. We conducted a case control study nested within a population-based cohort of all Quebec elderly dispensed respiratory medications and followed for at least 4 years during 1988-2001. There were 9,624 new cases of fracture of the hip or upper extremities and 191,622 age-matched control subjects (mean age of 81 years). The rate of any such fracture for current inhaled corticosteroid use was not elevated (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.92-1.03). For upper-extremity fracture, the rate increased by 12% (RR, 1.12; 95% CI, 1.04-1.19) with every 1,000-microg increase in the daily dose of inhaled corticosteroids, but not for hip fracture (RR, 0.97; 95% CI, 0.88-1.07). Among subjects followed for over 8 years, the rate of hip fracture was only elevated with daily doses of more than 2,000 microg of inhaled corticosteroids (RR, 1.61; 95% CI, 1.04-2.50). The rate was not elevated at any dose of nasal corticosteroids. In conclusion, the long-term use of inhaled and nasal corticosteroids at the usual recommended doses is not associated with a risk of fracture in older patients with respiratory disease.

Administration, Inhalation↗
PubMed2003

Inhaled corticosteroid use in asthma and the prevention of myocardial infarction.

BACKGROUND: Asthma patients may be at increased risk of cardiovascular outcomes due to hypoxemia from asthma exacerbations and bronchodilator-induced tachycardia. We investigated whether inhaled corticosteroids, which are known to improve asthma control and reduce exacerbations, are associated with a lower rate of myocardial infarction. METHODS: We used the Saskatchewan Health databases to form a population-based cohort of subjects aged 5 to 44 years who were using antiasthma drugs between 1975 and 1991. Subjects were followed until 1997, the age of 55 years, or death. A nested case-control approach was used where each subject with a first myocardial infarction was matched on calendar time, age, and sex with up to 10 controls randomly selected from the cohort. RESULTS: The cohort consisted of 30,569 subjects, including 105 patients with myocardial infarction who were matched with 933 controls. The adjusted rate ratio of myocardial infarction for inhaled corticosteroid use during the year before the index date was 0.56 (95% confidence interval [CI]: 0.32 to 0.99) as compared with no use. Myocardial infarction decreased by 12% (95% CI: 0% to 23%) with each additional canister used during this 1-year period. The rate ratio of myocardial infarction for inhaled corticosteroid use was 0.78 (95% CI: 0.41 to 1.51) among patients with milder asthma and 0.19 (95% CI: 0.04 to 0.97) among those with more severe asthma. CONCLUSION: Inhaled corticosteroid use may reduce the risk of myocardial infarction in asthma patients, particularly those with more severe disease.

Administration, Inhalation↗
PubMed2003

Antibiotics in primary prevention of stroke in the elderly.

BACKGROUND AND PURPOSE: An increasing number of reports have linked infections to atherosclerosis and thrombosis. Thus, use of antibiotics may lower the risk of developing cerebrovascular disease. We investigated whether antibiotic use is associated with the risk of stroke in elderly individuals treated for hypertension. METHODS: A cohort of 29 937 elderly subjects initiating antihypertensive therapy between 1982 and 1995 was formed from the Quebec healthcare insurance database. A nested case-control design was used in which each subject hospitalized with a primary discharge diagnosis of stroke between 1987 and 1995 was matched on calendar time to 5 randomly selected controls from the cohort. Conditional logistic regression was used to estimate odds ratios of stroke after adjustment for predisposing factors. RESULTS: We identified 1888 cases and 9440 controls. The overall adjusted odds ratio for current antibiotic use was 0.80 (95% confidence interval, 0.63 to 1.01), and that for recent use was 0.81 (95% confidence interval, 0.70 to 0.94). Penicillin was the only individual antibiotic class that showed a protective association across different time windows. No significant association was found between stroke risk and the use of fluoroquinolones, macrolides, tetracyclines, or cephalosporins. CONCLUSIONS: Although no clear, consistent associations between overall antibiotic use and cerebrovascular disease could be found, an intriguing association between penicillin use and stroke should be explored further.

Aged↗
PubMed2003

The impact of hepatitis C virus coinfection on HIV progression before and after highly active antiretroviral therapy.

To compare the impact of hepatitis C virus (HCV) coinfection on progression of HIV infection in the eras before and after the introduction of highly active antiretroviral therapy (HAART), the authors conducted a retrospective cohort study. One hundred twenty-five HCV+ patients and 1076 HCV- patients were studied; 83% of HCV+ patients were injection drug users. HCV+ subjects experienced no clear benefit from HAART. The adjusted hazard ratios (HRs) of opportunistic infection, death, and hospitalization were 0.74 (95% CI: 0.31-1.78), 1.78 (95% CI: 0.59-5.37), and 2.1 (95% CI: 0.90-4.90), respectively, comparing the post-HAART era with the pre-HAART era. In contrast, HCV- subjects experienced rate reductions for all outcomes. Comparable HRs for opportunistic infection, death, and hospitalization were 0.49 (95% CI: 0.37-0.64), 0.28 (95% CI: 0.19-0.41), and 0.51 (95% CI: 0.38-0.67), respectively. HCV+ subjects remained at increased risk for death and hospitalization post-HAART even after additional adjustment for antiretroviral use and time-updated CD4 cell and viral load measures. Deaths and hospitalizations in HCV+ patients were primarily for non-AIDS-defining infections and complications of injection drug use. HCV coinfection and comorbidity associated with injection drug use are preventing the realization of substantial health benefits associated with HAART.

Adult↗
PubMed2003

Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies.

Recent large-scale cohort studies that reported an important reduction in mortality and chronic obstructive pulmonary disease (COPD) morbidity with inhaled corticosteroids may be biased. We used a population-based cohort of Saskatchewan residents 55 years of age or over, first hospitalized for COPD during 1990 to 1997, to study this potential bias. These 979 subjects were followed for a year from discharge until their first readmission for COPD or death (389 subjects). Inhaled corticosteroid exposure was measured as any dispensing within 90 days after discharge. Cox's proportional hazards model was used to compare the time-fixed analysis employed in the recent studies with the alternative time-dependent analysis. The time-fixed adjusted rate ratio was 0.69 (95% CI: 0.55-0.86) for inhaled corticosteroid use within 90 days, whereas the time-dependent rate ratio was 1.00 (95% CI: 0.79-1.26). With the time-fixed analysis, the rate ratios were affected by the length of the exposure period, decreasing from 0.98 for a 15-day exposure period to 0.51 for 365 days, but remained stable between 1.06 and 0.94 with the time-dependent analysis. Inhaled corticosteroid use after hospitalization for COPD was not found to reduce mortality and morbidity. Although observational studies can be valuable, the recent reports of reductions in mortality and morbidity with inhaled corticosteroids are biased by their inappropriate allocation of exposure and analysis of immortal time.

Administration, Inhalation↗