Hip fractures attributable to corticosteroid use. Study of Osteoporotic Fractures Group.
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Administration, Inhalation↗
Biomedical subjects
S Suissa
Publications and source records attributed to S Suissa.
Association of inhaled corticosteroid use with cataract extraction in elderly patients.
CONTEXT: The use of systemic corticosteroids is a known risk factor for the development of cataracts. OBJECTIVE: To determine whether treatment with inhaled corticosteroids is associated with cataract extraction in the elderly. DESIGN: Case-control study. SETTING: Quebec universal health insurance program for all elderly (provincial health insurance plan database [RAMQ database]). PATIENTS: RAMQ enrollees 70 years and older. The 3677 cases were patients with a cataract extraction between 1992 and 1994. The 21868 controls were randomly selected from patients who did not have a diagnosis of cataract and matched to cases on the index date of the case. MAIN OUTCOME MEASURES: Odds ratio of cataract extraction in patients with prolonged cumulative exposure to inhaled corticosteroids compared with nonusers. RESULTS: Excluding patients with systemic steroid treatment and after adjusting for age, sex, diabetes, systemic hypertension, glaucoma, ophthalmic steroids, and the number of physician claims for services, use of inhaled corticosteroids for more than 3 years was associated with undergoing cataract extraction (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.53-6.13). For high average daily doses of beclomethasone or budesonide (>1 mg), the OR was elevated after more than 2 years of treatment (OR, 3.40; 95% CI, 1.49-7.76), whereas for low to medium doses (< or =1 mg) of these drugs, the OR was 1.63 (95% CI, 0.85-3.13) after 2 years. CONCLUSION: Prolonged administration of high doses of inhaled corticosteroids increases the likelihood of undergoing cataract extraction in elderly patients. Further studies are needed to investigate the risk of developing cataracts for low to medium doses over longer periods.
Administration, Inhalation↗
Exposure to allopurinol and the risk of cataract extraction in elderly patients.
OBJECTIVE: To determine whether exposure to allopurinol is associated with an increased risk of cataract extraction in elderly patients. METHODS: We conducted a case-control study using data from the Quebec universal health insurance program for all elderly patients. The 3677 cases were patients with a cataract extraction between 1992 and 1994. The 21,868 controls were randomly selected among patients not diagnosed with cataract and matched to cases on the date of the extraction. We determined the odds ratio of cataract extraction according to the cumulative dose and duration of allopurinol use relative to nonusers, using conditional logistic regression analysis. The analysis was adjusted for the effects of age, sex, diabetes mellitus, hypertension, glaucoma, and ophthalmic and oral corticosteroid exposure. RESULTS: A cumulative dose of allopurinol of more than 400 g or a duration of use of longer than 3 years were associated with an increased risk of cataract extraction, with odds ratios of 1.82 (95% confidence interval [CI], 1.18-2.80) and 1.53 (95% CI, 1.12-2.08), respectively. No increase in risk was observed for lower cumulative doses or shorter exposure periods. CONCLUSION: Long-term administration of allopurinol increases the risk of cataract extraction in elderly patients.
Aged↗
Antihypertensive drugs and the risk of gastrointestinal bleeding.
PURPOSE: Calcium channel blockers have been reported to increase the risk of gastrointestinal bleeding. We tested this hypothesis, and also assessed whether beta blockers decrease this risk. SUBJECTS AND METHODS: A nested case-control design within a population-based cohort of all 34,074 new users of beta blockers, angiotensin-converting enzyme (ACE) inhibitors, or calcium channel blockers in Saskatchewan, from 1990 to 1993 and followed up to March 1995, was used. We identified all 311 subjects hospitalized because of gastrointestinal bleeding during this period, each of whom was matched to 10 randomly selected controls. RESULTS: The rate of hospitalization for gastrointestinal bleeding was 3.0 per 1,000 per year. The adjusted rate ratio of gastrointestinal bleeding for current use of calcium channel blockers was 1.1 (95% confidence interval [CI] 0.8 to 1.4) and 0.66 (95% CI 0.44 to 0.98) for beta blockers compared with no current use of anti-hypertensive drugs. The adjusted rate ratio for ACE inhibitor use was 1.0 (95% CI 0.7 to 1.3) while that for diuretic use was 1.4 (95% CI 1.0 to 2.0). CONCLUSIONS: The use of calcium channel blockers does not appear to increase the risk of gastrointestinal bleeding in the first five years of treatment, while beta blockers may prevent this adverse event. The unexpected elevated risk associated with the use of diuretics needs to be investigated further.
Adult↗
Selection of controls in database case-control studies: glucocorticoids and the risk of glaucoma.
In case-control studies conducted using computerized databases, controls are often selected as a random sample from the base population. This representative choice of controls is intended to guard against selection bias. We show, using data from a database case-control study, that such a definition of controls may also lead to selection bias under two conditions: (1) if the target disease has a prolonged asymptomatic clinical course with its detection depending on a specific physical examination and (2) if exposed patients have a higher likelihood of having the disease detected than unexposed patients. The extent of the bias that could result from the use of randomly selected controls was investigated in the context of a case-control study of the risk of ocular hypertension or glaucoma associated with the use of glucocorticoids, conducted using the Quebec universal health insurance computerized databases. This article also illustrates that a computerized database can be useful to empirically explore opportunities for bias.
Aged↗
The effect of socio-demographic and crash-related factors on the prognosis of whiplash.
Whiplash injury, common after a motor vehicle crash, has a variable prognosis that is difficult to predict. To assess the role of various factors on this prognosis, we assembled a historical cohort of 3014 individuals who sustained a whiplash injury resulting from a motor vehicle crash in the Province of Quebec, Canada, in 1987 and were followed for 6 years. The data were obtained from the computerized databases created by the province's universal automobile insurance plan and police accident reports. The recovery time from whiplash, as measured by duration of compensation, was the primary outcome. Socio-demographic and crash-related factors measured at the time of the crash were investigated. The median recovery time for the cohort was 31 days, with 22% recovering within a week and 3% still not recovered after 1 year. For the 1551 subjects with a whiplash injury only, the socio-demographic factors that were found to be independently associated with a slower recovery from whiplash in this cohort are female gender, older age, having dependents, and not having full-time employment. The significant crash-related factors are occupancy in a truck or bus, being a passenger in the vehicle, colliding with a moving object, and being in a head-on or perpendicular collision. We classified the subjects according to a prediction score ranging from 0 to 11, devised from these factors. Subjects with a score of 0 to 2, that is those who had at most two risk factors present, had the fastest median recovery time of 19 days compared with 71 days for subjects who had a score of 6 or more. We conclude that several sociodemographic and crash-related factors are independently associated with a slow and costly recovery from whiplash injury. They are easily measurable at the time of the crash and combined so as to be simply incorporated in intervention programs aimed at early identification and management of whiplash patients with a poor prognosis.
Accidents, Traffic↗
First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma.
BACKGROUND: Early treatment with inhaled corticosteroids appears to improve clinical symptoms in asthma. Whether a first treatment initiated in the year following the recognition of asthma can prevent major outcomes such as admission to hospital has yet to be studied. METHODS: A case-control study nested within a cohort of 13,563 newly treated asthmatic subjects selected from the databases of Saskatchewan Health (1977-1993) was undertaken to investigate the effectiveness of a first treatment with inhaled corticosteroids in preventing admissions to hospital for asthma. Study subjects were aged between five and 44 years at cohort entry. First time users of inhaled corticosteroids were compared with first time users of theophylline for a maximum of 12 months of treatment. The two treatments under study were further classified into initial and subsequent therapy to minimize selection bias and confounding by indication. Odds ratios associated with hospital admissions for asthma were estimated using conditional logistic regression. Markers of asthma severity, as well as age and sex, were considered as potential confounders. RESULTS: Three hundred and three patients admitted to hospital with asthma were identified and 2636 matched controls were selected. subjects initially treated with regular inhaled corticosteroids were 40% less likely to be admitted to hospital for asthma than regular users of theophylline (odds ratio 0.6; 95% CI 0.4 to 1.0). The odds ratio decreased to 0.2 (95% CI 0.1 to 0.5) when inhaled corticosteroids and theophylline were given subsequently. CONCLUSION: The first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce the risk of admission to hospital for asthma by up to 80% compared with regular treatment with theophylline. This is probably due, at least in part, to reducing the likelihood of a worsening in the severity of asthma.
Administration, Inhalation↗
Inhaled corticosteroids and the prevention of readmission to hospital for asthma.
Despite the proven efficacy of inhaled corticosteroids in reducing airway inflammation and their increasing use for the treatment of asthma since the mid 1980s, hospitalization for asthma has been increasing in frequency in several countries. Only few studies, reporting contradictory results, have investigated the role of inhaled corticosteroids in the prevention of hospitalizations for asthma. Using a cohort of 2,059 hospitalized asthmatic patients between 5 and 54 yr of age, we estimated the effectiveness of inhaled corticosteroids in preventing a readmission to hospital for asthma as a function of the duration of therapy. The cohort was selected from the databases of Saskatchewan Health from 1977 to 1993. The rate ratio (RR) of a readmission for asthma varied with duration of regular therapy with inhaled corticosteroids. During the first 15 d of regular therapy, users of inhaled corticosteroids were as likely as nonusers of these medications to be readmitted for asthma with a RR of 1.2 (95% CI: 0.8-1.8). Subjects treated regularly with inhaled corticosteroids for at least 16 d and as long as 6 mo were 40% less likely to be readmitted for asthma (RR = 0.6; 95% CI: 0.4-0.9), while after 6 mo of regular treatment the protective effect disappeared (RR = 1.3; 95% CI: 0.7-2.4). We conclude that regular therapy with inhaled corticosteroids can substantially reduce the risk of a readmission for asthma after only 15 d of use. Confounding by severity appears as the most likely explanation for the disappearance of the beneficial effect after 6 mo of regular therapy.
Administration, Inhalation↗
External comparisons from nested case-control designs.
The nested case-control design, used to sample within cohorts, is usually employed for internal comparisons. We propose to use this design for external comparisons. We present two probability-weighted estimators of the expected number of cases under a given exposure, based on external rates, for two versions of the nested case-control design. These estimators are used, along with their variance estimators, to form confidence intervals for standardized mortality ratios. The estimators are practically unbiased, whereas the naive estimator that treats the nested case-control sample as a random sample of the cohort is clearly biased. An estimator from the alternative Cox model-based approach is found to be substantially biased when applied in this context. Comparing the proposed estimators for nested case-control designs to a corresponding estimator for the case-cohort design, we found that the correlation between follow-up time and exposure time (that is, the amount of time under the exposure effect) has an impact on which type of design is more efficient for external comparisons. A small correlation favors the case-cohort design and a large correlation the nested case-control design. We examine empirical properties of these estimators through computer simulations, using a cohort study of the incidence of second cancer in 2,189 patients with Hodgkin's disease.
Bias↗
The case-time-control design: further assumptions and conditions.
The case-time-control design is a strategy that was developed to tackle the problem of confounding by indication in the nonexperimental assessment of intended or known effects of drugs. By using subjects as their own controls, the case-time-control design, under an explicitly defined model, eliminates the biasing effect of unmeasured confounding factors in the situation where exposure varies over time. The correct application of this design is based on a specific model that contains inherent assumptions and imposes certain conditions for the approach to be valid. In a recent article, Greenland questioned the validity of the case-time-control design by presenting several "counterexamples." In this paper, we review the assumptions inherent to the validity of the case-time-control model. We show that the presumed counterexamples are not what they are claimed to be, simply because they do not conform to the logistic model explicitly underlying the case-time-control approach. These examples are shown to arise from an alternative model that includes a confounder by period interaction, a term expressly avoided in the case-time-control model. When the data from these examples are modified to satisfy the correct model, the resulting case-time-control estimates of the treatment odds ratio are exactly 2, the true treatment effect. We clarify the necessity of this assumption in the context of matching in epidemiology. We also discuss briefly the assumptions of conditional independence and carryover effects.
Bias↗
A population-based, randomized clinical trial on back pain management.
STUDY DESIGN: Population-based randomized clinical trial. OBJECTIVES: To develop and test a model of management of subacute back pain, to prevent prolonged disability. SUMMARY OF BACKGROUND DATA: The present management of back pain seems inadequate, and development of innovative models has been urged. METHODS: A model for the treatment of subacute work-related back pain has been developed and evaluated in a population-based randomized clinical trial. Workers (n = 130) from eligible workplaces in the Sherbrooke area (N = 31), who had been absent from work for more than 4 weeks for back pain, were randomized, based on their workplace, in one of four treatment groups: usual care, clinical intervention, occupational intervention, and full intervention (a combination of the last two). The duration of absence from regular work and from any work was evaluated using survival analysis. Functional status and pain were compared at study entry and after 1 year of follow-up. RESULTS: The full intervention group returned to regular work 2.41 times faster than the usual care intervention group (95% confidence interval 1.19-4.89; P < 0.01). The specific effect of the occupational intervention accounted for the most important part of this result, with a rate ratio of return to regular work of 1.91 (95% confidence interval = 1.18-3.10; P < 0.01). Pain and disability scales demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups, compared with the trend in the usual care intervention group. CONCLUSIONS: Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain.
Adolescent↗
Inhaled corticosteroids and the risk of cataracts.
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Administration, Inhalation↗
Risk of hypoglycemia with antihypertensive medication.
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Antihypertensive Agents↗
Risk of ocular hypertension or open-angle glaucoma in elderly patients on oral glucocorticoids.
BACKGROUND: Ocular hypertension and open-angle glaucoma are well-known side-effects of treatment with topical ophthalmic glucocorticoids. There is uncertainty about the risk of these disorders with oral glucocorticoid therapy. METHODS: Data from the Quebec universal health insurance programme for the elderly were used to identify 9793 patients with a new diagnosis of ocular hypertension or open-angle glaucoma, or on newly prescribed treatment for these disorders (cases). 38,325 controls were randomly selected from ophthalmology patients seen in the same month and year as the case (index date). Current use of oral glucocorticoids was defined as that within 14 days of the index date. All glucocorticoid doses were converted to the equivalent amount of hydrocortisone. The case-control analysis was done by conditional logistic regression and adjusted for age, sex, systemic hypertension, diabetes mellitus, ophthalmic glucocorticoids, glucocorticoid injections, and variables related to general health. FINDINGS: The mean ages of cases and controls were similar (74.9 [SD 6.3] vs 74.7 [6.4]). The adjusted odds ratio of ocular hypertension or open-angle glaucoma for current users of oral glucocorticoids compared with non-users was 1.41 (95% CI 1.22-1.63). There was a dose-related increase in the adjusted odds ratios for current users: 1.26 (1.01-1.56) for less than 40 mg per day of hydrocortisone, 1.37 (1.06-1.76) for patients on 40-79 mg per day, and 1.88 (1.40-2.53) for patients on 80 mg or more per day. The odds ratios also increased with the duration of treatment over the first 11 months of exposure. INTERPRETATION: The use of oral glucocorticoids increases the risk of ocular hypertension or open-angle glaucoma in elderly patients. In patients in this age-group who need long-term treatment with high doses of oral glucocorticoids, monitoring of intraocular pressure may be justified.
Administration, Oral↗
Benzodiazepine use and the risk of motor vehicle crash in the elderly.
CONTEXT: Benzodiazepines, used by a sizable number of the elderly population, may affect the ability to drive and thus increase the risk of a motor vehicle crash. Epidemiologic studies of this question have produced inconsistent results that may be due to the different effects of long- and short-half-life benzodiazepines and variations in their duration of use. OBJECTIVE: To determine whether the use of benzodiazepines of either long- or short-elimination half-life is associated with the risk of injurious motor vehicle crash in the elderly. DESIGN AND SETTING: Nested case-control design within a cohort of 224,734 drivers from the Canadian province of Quebec, aged 67 to 84 years, followed up from 1990 to 1993. Computerized data for the study were obtained from provincial driver's license files, police reports of injurious crashes, and health insurance records. PATIENTS: We identified all 5579 drivers involved in an injurious crash (cases) and a random sample of 10 controls per case selected from a subcohort of 13,256 subjects. MAIN OUTCOME: Involvement of a cohort member as a driver in a motor vehicle crash in which at least 1 person (not necessarily the driver) sustained bodily injury. RESULTS: The adjusted rate ratio of crash involvement within the first week of long-half-life benzodiazepine use was 1.45 (95% confidence interval [CI], 1.04-2.03). The rate ratio for continuous use of longer duration up to 1 year was slightly lower but remained significant (rate ratio, 1.26; 95% CI, 1.09-1.45). In contrast, there was no increased risk after the initiation of treatment with short-half-life benzodiazepines (rate ratio, 1.04; 95% CI, 0.81-1.34) or with their continued use (rate ratio, 0.91; 95% CI, 0.82-1.01). CONCLUSIONS: Brief or extended periods of exposure to long-half-life benzodiazepines are associated with an increased risk of motor vehicle crash involvement in the elderly population. There is no such elevated risk for short-half-life benzodiazepines.
Accidents, Traffic↗
Albuterol in mild asthma.
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Administration, Inhalation↗
Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma.
OBJECTIVE: To determine whether the use of inhaled and nasal glucocorticoids is associated with an increased risk of ocular hypertension or open-angle glaucoma. DESIGN: Case-control study. SETTING: Québec universal health insurance program for all elderly (registered in the Régie de l'assurance maladie du Québec [RAMQ] database). PATIENTS: Enrollees in the RAMQ database aged 66 years and older. The 9793 case patients were ophthalmology patients with a new diagnosis of borderline glaucoma or open-angle glaucoma or were newly started on treatment for ocular hypertension or glaucoma between 1988 and 1994. The 38,325 control patients were randomly selected among noncases with ophthalmologist visits in the same month and year as the case event (index date). MAIN OUTCOME MEASURES: The odds ratio (OR) of ocular hypertension or open-angle glaucoma was determined in patients using inhaled or nasal glucocorticoids relative to nonusers, using conditional logistic regression analysis. The OR was adjusted for age, sex, diabetes mellitus, systemic hypertension, use of ophthalmic and oral glucocorticoids, and characteristics of health care system use in the year before the index date. RESULTS: Overall, current use of inhaled and nasal glucocorticoids was not associated with an increased risk of ocular hypertension or open-angle glaucoma. Current users of high doses of inhaled steroids prescribed regularly for 3 or more months were at an increased risk with an OR of 1.44 (95% confidence interval, 1.01-2.06). CONCLUSION: Prolonged administration of high doses of inhaled glucocorticoids increases the risk of ocular hypertension or open-angle glaucoma. This finding suggests that in these patients intraocular pressure monitoring may be warranted.
Administration, Inhalation↗
Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma. A randomized, double-blind, placebo-controlled trial.
BACKGROUND: The increasing costs of managing asthma are due in part to the introduction of new medications, such as leukotriene receptor antagonists. These antagonists interfere with the action of leukotrienes, which are implicated in bronchoconstriction and the formation of airway edema in patients with asthma. Leukotriene receptor antagonists must be shown to be clinically and economically effective for their clinical use to be justified. OBJECTIVE: To assess the clinical and economic effectiveness of zafirlukast, a leukotriene receptor antagonist, in patients with mild-to-moderate asthma who might benefit from regular anti-inflammatory therapy. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. SETTING: 28 outpatient clinics. PATIENTS: 146 patients with mild-to-moderate asthma who were 12 years of age or older, had not smoked cigarettes in the previous 6 months, had a smoking history of less than 10 pack-years, had an FEV1 at least 55% of the predicted value with no upper limit, had demonstrated bronchial hyperresponsiveness, and were symptomatic during the 7-day run-in period. All patients were seen every 2 to 3 weeks for 13 weeks. INTERVENTION: 103 patients received zafirlukast (20 mg twice daily), and 43 patients received placebo (twice daily). All patients received inhaled beta-agonists as needed. MEASUREMENTS: Data were obtained from medical examinations, patient questionnaires, and daily diaries. The clinical effectiveness outcomes were days per month without asthma symptoms, limitation of activity, use of beta-agonists, sleep disturbance, and episodes of asthma (the latter was a composite measure made up of the first four outcomes plus the occurrence of adverse events). The economic effectiveness outcomes were frequency and type of unscheduled health care contacts, use of beta-agonist inhalers, consumption of nonasthma medications, and days of absence from work or school. RESULTS: The zafirlukast group had 89% more days without symptoms (adjusted rates, 7.0 compared with 3.7 days per month; P = 0.03), 89% more days without use of beta-agonists (adjusted rates, 11.3 compared with 6.0 days per month; P = 0.001), and 98% more days without episodes of asthma (adjusted rates, 10.1 compared with 5.1 days per month; P = 0.003). They also had 55% (95% CI, 19% to 74%) fewer health care contacts (18.5 compared with 40.7 per 100 per month; P = 0.007) and 55% (CI, 3% to 79%) fewer days of absence from work or school (15.6 compared with 35.0 per 100 per month; P = 0.04). They used 17% fewer canisters of inhaled beta-agonists (P = 0.17) and 19% less nonasthma medication (P < 0.2). CONCLUSIONS: A daily regimen of zafirlukast added to as-needed inhaled beta-agonists is more effective than beta-agonists alone in treating mild-to-moderate asthma. The clinical and economic effectiveness of zafirlukast, a potential alternative to inhaled corticosteroids, provides further impetus to use regular "preventive" therapy in patients with mild-to-moderate asthma.
Absenteeism↗