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Biomedical subjects

Samy Suissa

Publications and source records attributed to Samy Suissa.

At least 37 records · Page 2Linked to original sources
PubMed2006

Asthma mortality in portugal : impact of treatment with inhaled corticosteroids and leukotriene receptor antagonists.

OBJECTIVE: To determine whether the use of inhaled corticosteroids or leukotriene receptor antagonists (LTRAs) has had an impact on asthma mortality in Portugal during the period 1991-2001. METHODS: A population-based ecological study was conducted for the period 1991-2001. Yearly asthma death rates were computed for all ages. Data on sales of inhaled corticosteroids and LTRAs were obtained and expressed in defined daily doses (DDDs)/year. The association between the yearly rate of asthma deaths and consumption of these medications was estimated using Poisson regression. RESULTS: The rate of asthma death decreased steadily from 39.4 per million inhabitants in 1991 to 14.2 in 2001. At the same time, the use of inhaled corticosteroids in the population increased from 5.8 to 22.2 million DDDs per year. The adjusted rate ratio of asthma death was 0.85 (95% CI 0.78, 0.92) for every additional 5 million DDDs of inhaled corticosteroids per year and 0.84 (95% CI 0.70, 1.02) for every additional 5 million DDDs of LTRAs per year. CONCLUSION: The increasing use of inhaled corticosteroids and leukotriene receptor antagonists during the 1990s in Portugal appears to have contributed to the reduction in asthma mortality in that country.

Administration, Inhalation↗
PubMed2006

Assessing a whiplash management model: a population-based non-randomized intervention study.

OBJECTIVE: To evaluate the effectiveness of a multidisciplinary clinical management approach for whiplash-associated disorders (WAD) following a motor vehicle injury in Quebec. METHODS: A clinical management model was implemented in 5 geographic regions of the Province of Quebec, Canada, in 7 hospitals and 19 clinics. A 2-group population-based parallel design was used to assess its effectiveness. All patients with a new whiplash injury seen in these 26 centers between March and September, 2001 were entered into the Whiplash Management Model (experimental group). A reference group included all subjects who had a whiplash injury during this same period but were not seen in these 26 intervention centers. All subjects were followed for up to a year. The outcome variables were time on compensation, time to file closure, and total direct costs. RESULTS: A total of 288 patients with WAD were identified in the experimental group and 1,875 patients in the reference group. The rate of ending of compensation was significantly higher in patients who received the experimental treatment model than those receiving the reference treatment approach (rate ratio, RR: 3.2; 95% confidence interval, CI: 2.8-3.6). The rate of file closure was also significantly higher with the experimental treatment (RR: 1.5; 95% CI: 1.2-1.8). The average cost per patient was significantly reduced with the experimental intervention. CONCLUSION: A coordinated whiplash management approach can lead to earlier return to work and lower costs for patients who have sustained a whiplash injury.

Accidents, Traffic↗
PubMed2005

Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease.

CONTEXT: Recent reports suggest an increasing occurrence and severity of Clostridium difficile-associated disease. We assessed whether the use of gastric acid-suppressive agents is associated with an increased risk in the community. OBJECTIVE: To determine whether the use of gastric acid-suppressive agents increases the risk of C difficile-associated disease in a community population. DESIGN, SETTING, AND PATIENTS: We conducted 2 population-based case-control studies using the United Kingdom General Practice Research Database (GPRD). In the first study, we identified all 1672 cases of C difficile recorded between 1994 and 2004 among all patients registered for at least 2 years in each practice. Each case was matched to 10 controls on calendar time and the general practice. In the second study, a subset of these cases defined as community-acquired, that is, not hospitalized in the prior year, were matched on practice and age with controls also not hospitalized in the prior year. MAIN OUTCOME MEASURES: The incidence of C difficile and risk associated with gastric acid-suppressive agent use. RESULTS: The incidence of C difficile in patients diagnosed by their general practitioners in the General Practice Research Database increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in 2004. The adjusted rate ratio of C difficile-associated disease with current use of proton pump inhibitors was 2.9 (95% confidence interval [CI], 2.4-3.4) and with H2-receptor antagonists the rate ratio was 2.0 (95% CI, 1.6-2.7). An elevated rate was also found with the use of nonsteroidal anti-inflammatory drugs (rate ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSIONS: The use of acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk of community-acquired C difficile. The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further.

Aged↗
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

Bias in observational study of the effectiveness of nasal corticosteroids in asthma.

BACKGROUND: A recent observational study suggests that intranasal corticosteroids used to treat allergic rhinitis are effective at preventing asthma outcomes, such as emergency visits. The approach to data analysis may have led to biased results because of misclassification of immortal time. OBJECTIVE: To illustrate the bias in the cohort approach and to present the proper time-dependent analysis by replicating the recent study using data from another source. METHODS: From an existing cohort of 30,569 patients with asthma age 5 to 44 years and identified from the Saskatchewan Health databases (1975-1997), we formed the cohort of all subjects who were in the source population between January 1, 1989, and December 31, 1991. Subjects were followed to the first asthma hospitalization. All prescriptions dispensed during follow-up were identified. We replicated the time-fixed approach to data analysis used in the recent study and compared it with time-dependent approaches. RESULTS: The cohort included 20,173 subjects, of whom 1849 were hospitalized for asthma between January 1, 1989, and December 31, 1991. The time-fixed approach misclassified more than 5000 person-years of follow-up, corresponding to 44% of the exposed person-time. As a result, the rate ratio of asthma hospitalization after any use of nasal corticosteroids (NCSs) was 0.57 by the biased time-fixed approach compared with 1.13 by the proper time-dependent approach. The time-fixed approach produced a paradoxical protective effect of NCS with 1 or less canisters dispensed per year (odds ratio, 0.47), which was further exaggerated when the cohort was extended to 5 years (odds ratio, 0.33). Adjusted time-dependent analyses found no protective effect, even when NCSs were dispensed regularly (rate ratio, 1.10; 95% CI, 0.54-2.21). CONCLUSION: The time-fixed approach to the analysis of the effectiveness of NCSs on asthma outcomes leads, by its inherent misclassification of immortal time, to a considerable exaggeration of the protective effect of these medications in preventing severe asthma exacerbations.

Administration, Inhalation↗
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

Cardiovascular morbidity and mortality in COPD.

STUDY OBJECTIVE: COPD and cardiovascular disease (CVD) share common risk factors. We undertook to estimate rates of hospitalization and death from CVD in COPD patients relative to the general population. DESIGN AND SETTING: A cohort of patients > or = 55 years old receiving a first treatment for COPD between 1990 and 1997 was formed from the Saskatchewan Health databases. All hospitalizations and deaths between cohort entry and the end of 1999 were identified. RESULTS: The cohort included 5,648 individuals and generated 23,426 person-years (PY) of follow-up. The overall rates of cardiovascular morbidity and mortality were 177.2 and 41 per 1,000 PY, respectively. Cardiovascular morbidity and mortality rates were higher in the COPD cohort than in the general population (standardized rate ratios of 1.9 and 2.0, respectively). More hospitalizations for CVD than for COPD itself were reported. Among CVDs, heart failure represented the most frequent cause of hospitalization (58.8 per 1,000 PY). CVD and more specifically ischemic heart disease (19.6 per 1,000 PY) were reported as a more frequent cause of death than COPD itself (15.5 per 1,000 PY). CONCLUSION: CVD is more frequent in COPD patients than in the general population and may represent a burden greater than that of lung disease itself.

Aged↗
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↗
PubMed2005

The early natural history of nephropathy in Type 1 Diabetes: III. Predictors of 5-year urinary albumin excretion rate patterns in initially normoalbuminuric patients.

Predictors of albumin excretion rate (AER) abnormalities could provide earlier indicators of diabetic nephropathy risk. Data from the Natural History Study, a prospective 5-year observation of renal structure and function in young type 1 diabetic patients, were examined for predictors of AER patterns in normoalbuminuric type 1 diabetic patients. Included were 170 patients (96 females) (aged 16.7 +/- 5.9 years, duration of diabetes 8.0 +/- 4.3 years) with normal blood pressure, normoalbuminuria (AER <20 microg/min), and eight or more follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were determined quarterly and glomerular filtration rate (GFR) annually. Persistent microalbuminuria (PMA) was defined as 20-200 microg/min in two of three consecutive values within 6-12 months. Four different AER patterns were identified. Group 1 (n = 99): all values <20 microg/min. Group 2 (n = 49): intermittent levels >20 microg/min but not meeting microalbuminuria criteria. Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group 4 (n = 8): microalbuminuria at study exit. Group 4 (497 +/- 95 nm, P < 0.01) and group 3 (464 +/- 113 nm, P = 0.03) patients had greater baseline glomerular basement membrane (GBM) width versus group 1 (418 +/- 67 nm). Baseline GFR in group 4 (163 +/- 37 ml.min(-1). 1.73 m(-2)) was higher than group 1 (143 +/- 28 ml.min(-1) . 1.73 m(-2), P = 0.04). A1C was higher in group 2 (9.0 +/- 1.2%) than group 1 (8.4 +/- 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR were predictors of PMA. Since 64% of the patients that developed microalbuminuria reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by current microalbuminuria criteria is unclear.

Adolescent↗
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↗