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Biomedical subjects

S Suissa

Publications and source records attributed to S Suissa.

At least 37 records · Page 2Linked to original sources

A clinical trial of estrogen-replacement therapy after ischemic stroke.

BACKGROUND: Observational studies have suggested that estrogen-replacement therapy may reduce a woman's risk of stroke and death. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of estrogen therapy (1 mg of estradiol-17beta per day) in 664 postmenopausal women (mean age, 71 years) who had recently had an ischemic stroke or transient ischemic attack. Women were recruited from 21 hospitals in the United States and were followed for the occurrence of stroke or death. RESULTS: During a mean follow-up period of 2.8 years, there were 99 strokes or deaths among the women in the estradiol group, and 93 among those in the placebo group (relative risk in the estradiol group, 1.1; 95 percent confidence interval, 0.8 to 1.4). Estrogen therapy did not reduce the risk of death alone (relative risk, 1.2; 95 percent confidence interval, 0.8 to 1.8) or the risk of nonfatal stroke (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.4). The women who were randomly assigned to receive estrogen therapy had a higher risk of fatal stroke (relative risk, 2.9; 95 percent confidence interval, 0.9 to 9.0), and their nonfatal strokes were associated with slightly worse neurologic and functional deficits. CONCLUSIONS: Estradiol does not reduce mortality orthe recurrence of stroke in postmenopausal women with cerebrovascular disease. This therapy should not be prescribed for the secondary prevention of cerebrovascular disease.

Aged↗

Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group.

BACKGROUND: There has been some concern that vaccination may precipitate the onset of multiple sclerosis or lead to relapses. Since the recent hepatitis B vaccination program in France, there have been new reports of an increased risk of active multiple sclerosis after vaccination. METHODS: We conducted a case-crossover study to assess whether vaccinations increase the risk of relapse in multiple sclerosis. The subjects were patients included in the European Database for Multiple Sclerosis who had a relapse between 1993 and 1997. The index relapse was the first relapse confirmed by a visit to a neurologist and preceded by a relapse-free period of at least 12 months. Information on vaccinations was obtained in a standardized telephone interview and confirmed by means of medical records. Exposure to vaccination in the two-month risk period immediately preceding the relapse was compared with that in the four previous two-month control periods for the calculation of relative risks, which were estimated with the use of conditional logistic regression. RESULTS: Of 643 patients with relapses of multiple sclerosis, 15 percent reported having been vaccinated during the preceding 12 months. The reports of 94 percent of these vaccinations were confirmed. Of all the patients, 2.3 percent had been vaccinated during the preceding two-month risk period as compared with 2.8 to 4.0 percent who were vaccinated during one or more of the four control periods. The relative risk of relapse associated with exposure to any vaccination during the previous two months was 0.71 (95 percent confidence interval, 0.40 to 1.26). There was no increase in the specific risk of relapse associated with tetanus, hepatitis B, or influenza vaccination (range of relative risks, 0.22 to 1.08). Analyses based on risk periods of one and three months yielded similar results. CONCLUSIONS: Vaccination does not appear to increase the short-term risk of relapse in multiple sclerosis.

Adult↗

The relation between initial symptoms and signs and the prognosis of whiplash.

Whiplash, a common injury following motor vehicle crashes, is associated with high costs and a prognosis that is variable and difficult to predict. We studied the profile of recovery from whiplash and assessed whether presenting signs and symptoms directly after the crash were predictive of whiplash prognosis. We formed a population-based incident cohort of all 2627 individuals who sustained a whiplash injury resulting from a motor vehicle crash in the province of Québec, Canada, in 1987, and followed these patients for up to 7 years. The data on signs and symptoms were obtained from the medical charts kept by the universal automobile insurance plan (Société de l'assurance automobile du Québec), which covers all 7 million residents of the province, while data on the outcome--the recovery time from whiplash--was obtained from their databases. The median recovery time was 32 days, and 12% of subjects had still not recovered after 6 months. The signs and symptoms that were found to be independently associated with a slower recovery from whiplash, besides female gender and older age, are neck pain on palpation, muscle pain, pain or numbness radiating from the neck to arms, hands or shoulders, and headache. Together, these factors in older females (age 60) predicted a median recovery time of 262 days, compared with 17 days for younger males (age 20) who do not have this profile. In contrast, using a classification of injury severity previously proposed by the Québec Whiplash Associated Disorders Task Force, the median recovery time varied from 17 to only 123 days. We conclude that whiplash patients presenting with several specific musculoskeletal and neurological signs and symptoms will have a longer recovery period. These patients can easily be identified and closely monitored and targeted for the evaluation of early intervention programmes aimed at managing whiplash patients with a poor prognosis.

Accidents, Traffic↗

Meta-analysis comparing newer antipsychotic drugs for the treatment of schizophrenia: evaluating the indirect approach.

BACKGROUND: Meta-analysis is a useful method to assess the efficacy of newer antipsychotic drugs compared with older drugs or placebo. However, few trials directly compare novel drugs to each other. OBJECTIVE: The purpose of this study was to evaluate the method of indirect meta-analysis by applying it to data on olanzapine versus haloperidol and risperidone versus haloperidol to enable a comparison between olanzapine and risperidone. METHODS: Published randomized controlled trials (RCTs) of risperidone, olanzapine, and/or haloperidol were identified through literature searches (1983 to 1999) of the MEDLINE, Current Contents, and HealthSTAR databases and reviewed. Data for the Brief Psychiatric Rating Scale (BPRS) total score, the Positive and Negative Syndrome Scale (PANSS) negative subscale, the percentage of patients using anticholinergic drugs, and the percentage of patients dropping out due to lack of efficacy, side effects, or any cause were extracted and combined using the indirect method. These findings were compared with those from a direct comparative study of olanzapine and risperidone. RESULTS: The literature search yielded 8 RCTs comparing risperidone to haloperidol and 3 comparing olanzapine to haloperidol. Only 1 trial directly comparing olanzapine and risperidone was found. In this trial, the change in BPRS total and PANSS negative subscale scores tended to be higher with olanzapine by 1.80 and 1.10, respectively, but these differences were not statistically significant. Indirect meta-analysis yielded similar results. Changes in both BPRS total scores and PANSS negative subscale scores tended to be higher with olanzapine by 0.37 and 0.54, respectively, and again, the differences were not statistically significant. In the indirect meta-analysis, the rate of anticholinergic drug use was 19.5% greater among patients treated with risperidone than among patients treated with olanzapine (P < 0.05). In the direct comparative RCT, the rate was 13.1% higher among patients treated with risperidone (P < 0.05). The dropout rates were similar for patients treated with risperidone and those treated with olanzapine in both analyses. CONCLUSION: An indirect meta-analysis of studies comparing olanzapine with haloperidol and risperidone with haloperidol yielded conclusions similar to those found in a direct comparative RCT of olanzapine and risperidone.

Antipsychotic Agents↗

Inhaled corticosteroids: impact on asthma morbidity and mortality.

Inhaled corticosteroids are now recommended as first-line therapy for asthma. Although these drugs clearly improve the symptoms of the disease and the associated physiologic abnormalities, epidemiologic studies provide important information on their effectiveness in preventing asthma morbidity and mortality. We review the evidence regarding the role of inhaled corticosteroids in the prevention of asthma fatality and hospitalization. In the process, we discuss the methodologic complexities of the nonexperimental studies and the implications of the methodologic issues on the evaluation of the impact of these drugs. Eight of the cohort and ecologic studies conducted to date strongly suggest that inhaled corticosteroids, when taken regularly, decrease the number of hospitalizations for asthma by up to 80%. For asthma death, the results of 11 investigations appear less consistent, especially those of several cohort and case-control studies whose principal objective was to examine not the benefit of inhaled corticosteroids but the adverse effects of other drug classes. Much of the inconsistency in the results, however, can be explained by weaknesses in study design and analysis-in particular, the failure to consider exposure in terms of regular use of inhaled corticosteroids. When the most recent study involving the use of the Saskatchewan databases is considered, it is evident that regular treatment with conventional or low-dose inhaled cortico-steroids results in a significant reduction in fatalities due to asthma. In all, the evidence to date strongly indicates that regular use of inhaled corticosteroids, even at low doses, would prevent the major portion of asthma hospitalizations and deaths.

Administration, Inhalation↗

The impact of combined inhaled bronchodilator therapy in the treatment of COPD.

BACKGROUND: Treatment guidelines recommend concomitant use of ipratropium bromide and inhaled beta2-agonists as severity of COPD progresses. While the use of these two agents in a single inhaler may enhance patient compliance and result in cost savings, it may, by itself, increase medication use. We assessed whether the introduction of a combined inhaled bronchodilator in the treatment of COPD modifies the use and costs related to prescribed medications. METHOD: A cohort of subjects > or =45 years old initiating treatment with either a combined inhaled bronchodilator (641 subjects) or ipratropium bromide and inhaled beta2 -agonist (411 subjects) between July 1, 1996, and June 30, 1997, was identified using the Saskatchewan Health databases. The primary outcomes were prescribed medication usage and the subsequent related costs during a 1-year follow-up period. Poisson regression analysis was used to estimate rate ratios (RRs) adjusted for drug use and hospitalization during the year prior to cohort entry. RESULTS: The adjusted RR of inhaled bronchodilator use was elevated for combined inhaled bronchodilator therapy (adjusted RR, 1.16; 95% confidence interval [CI], 1.07 to 1.26). However, the overall costs associated with these inhaled bronchodilators were reduced with combined inhaled bronchodilator therapy (adjusted mean ratio, 0.83; 95% CI, 0.76 to 0.92). The rate of use of other respiratory drugs and antibiotics was similar (adjusted RR, 1.03; 95% CI, 0.93 to 1.16). Applying the rate ratio for cost savings to all new, combined inhaled bronchodilator users led to estimated annual savings in Canadian dollars of 103,468 dollars (95% CI, 48,694 dollars to 146,082 dollars) in this province. CONCLUSION: The introduction of a simpler bronchodilator dosing regimen did not significantly alter the treatment of COPD and resulted in appreciable cost savings.

Administration, Inhalation↗

A multinational evaluation of the efficacy, safety and acceptability of the Protectaid contraceptive sponge.

OBJECTIVE: The Protectaid sponge (Gefar Pharma, Switzerland) is a new feminine barrier contraceptive method containing three low-dose spermicidal agents. In order to evaluate its efficacy and safety profiles, an international, multicenter study has been conducted in four countries. METHODS: Healthy, presumably fertile and sexually active women were enrolled in this study and were followed at 15 days, 3, 6, 9 and 12 months. Contraceptive efficacy was assessed by a pregnancy test, while safety was evaluated by performing gynecological examinations as well as reporting adverse events. The 'acceptability' of the sponge by the women was assessed through a standard questionnaire. RESULTS: A total of 129 women were enrolled in the study, generating 1182 cycles of use of the sponge. The overall efficacy rate was 77%, with no significant influence of age or parity. Acceptability was high, with 85% of subjects being symptom- or problem-free while using the sponge. Finally, the safety profile was very good, with no clinically significant evidence of local or systemic adverse reactions. CONCLUSION: The new Protectaid sponge is a safe and effective non-hormonal contraceptive method for women.

Administration, Intravaginal↗

Low-dose inhaled corticosteroids and the prevention of death from asthma.

BACKGROUND: Although inhaled corticosteroids are effective for the treatment of asthma, it is uncertain whether their use can prevent death from asthma. METHODS: We used the Saskatchewan Health data bases to form a population-based cohort of all subjects from 5 through 44 years of age who were using antiasthma drugs during the period from 1975 through 1991. We followed subjects until the end of 1997, their 55th birthday, death, emigration, or termination of health insurance coverage; whichever came first. We conducted a nested case-control study in which subjects who died of asthma were matched with controls within the cohort according to the length of follow-up at the time of death of the case patient (the index date), the date of study entry, and the severity of asthma. We calculated rate ratios after adjustment for the subject's age and sex; the number of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists, and oral corticosteroids in the year before the index date; the number of canisters of inhaled beta-adrenergic agonists used in the year before the index date; and the number of hospitalizations for asthma in the two years before the index date. RESULTS: The cohort consisted of 30,569 subjects. Of the 562 deaths, 77 were classified as due to asthma. We matched the 66 subjects who died of asthma for whom there were complete data with 2681 controls. Fifty-three percent of the case patients and 46 percent of the control patients had used inhaled corticosteroids in the previous year, most commonly low-dose beclomethasone. The mean number of canisters was 1.18 for the patients who died and 1.57 for the controls. On the basis of a continuous dose-response analysis, we calculated that the rate of death from asthma decreased by 21 percent with each additional canister of inhaled corticosteroids used in the previous year (adjusted rate ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death from asthma during the first three months after discontinuation of inhaled corticosteroids was higher than the rate among patients who continued to use the drugs. CONCLUSIONS: The regular use of low-dose inhaled corticosteroids is associated with a decreased risk of death from asthma.

Administration, Inhalation↗

Relationship between nonphenacetin combined analgesics and nephropathy: a review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy.

BACKGROUND: The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. METHOD: A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy. RESULTS: The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect. CONCLUSION: The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.

Acetaminophen↗

Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.

The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.

Adult↗

Double blind randomized clinical trial examining the efficacy of bupivacaine suprascapular nerve blocks in frozen shoulder.

OBJECTIVE: To determine whether the pain, contracture, and disability associated with idiopathic frozen shoulder are diminished by a series of 3 indirect bupivacaine suprascapular nerve blocks delivered in an ambulatory care clinic. METHODS: A double blind randomized controlled trial of patients referred by primary care and specialty clinics in Montreal to an ambulatory tertiary care academic facility. Patients and controls underwent a series of 3 indirect suprascapular nerve blocks at 7 day intervals using either 10 c.c. bupivacaine 0.5 (Marcaine) in the treatment group or 10 c.c. of physiological saline in controls. Subjects in both groups were taught a program of shoulder range of motion exercises to be done at home. The primary outcome measure was the McGill-Melzack Pain Questionnaire (MPQ) short form at 1 month post-randomization (2 weeks after last injection). The secondary outcome measures were disability measured by the simple shoulder test and glenohumeral joint contracture measured by shoulder range of motion measurements. RESULTS: Thirty-four subjects were randomized from 58 screened. Average age of subjects was 52 years. Mean duration of pain prior to randomization was one year. Dropout rate was 11% in the treatment group, 30% in the placebo group. A 64% reduction in pain in the treatment group versus 13% in the placebo group was observed at one month as measured by the MPQ multidimensional pain descriptors score (p = 0.03). A nonsignificant 15.8% improvement in shoulder function in the treatment group versus 4% in the placebo group (p = 0.24) was also noted. No improvement in shoulder range of movement was noted. No side effects other than transient vagal symptoms and local tenderness at the injection site were reported. CONCLUSION: The use of bupivacaine suprascapular nerve blocks was effective in reducing the pain of frozen shoulder at one month. Clinical studies with a larger number of subjects and a longer study period will help determine the duration and nature of the effect of bupivacaine suprascapular nerve blocks in treating the pain, disability, and glenohumeral joint contracture of frozen shoulder.

Adult↗

First lifetime back pain and psychiatry treatment: psychological factors and recovery in compensated workers.

The role of psychological factors in recovery from first lifetime low back pain (LBP) was explored in this study. Consecutive clients from one physiatry clinic in Montreal who had LBP of less than 3 months' duration, were on sick leave and receiving workers' compensation benefits, and reported the current event as first lifetime LBP were enrolled. Psychological factors that fluctuate with current events (Psychiatric Symptom Index) and remain stable over time (General Well Being Scale) were assessed. Outcomes were late return to work (> 31 days) and 1 year incidence of compensated recurrence. Results from two multivariate models indicated lower psychological distress predicted late return to work, and higher well being, higher aggressiveness, and lower anxiety predicted compensated recurrence. Researchers concluded psychological factors do not impact clients with all types of LBP in the same way. For individuals lacking prior LBP experience, better psychological functioning increased lengthy work absence. Thus, awareness of the clients' psychological profiles and previous LBP experiences may benefit recovery.

Adult↗

Maternal smoking and childhood asthma.

The role of maternal smoking as a causal factor for the incidence of childhood asthma is still not clearly established. It was investigated among 3- and 4-year-old-child incident cases confirmed by a 6-year follow-up (n = 294) and cases who no longer had symptoms after diagnosis (n = 110). The study took place in Montréal, Canada, between 1988 and 1997. Persistent and transient cases were compared with their respective controls from the original case-control study of incidence. The odds ratio for heavy maternal smoking adjusted for known risk factors for asthma was 3.84 (95% confidence interval: 1.68, 8.76) among persistent cases and close to one among transient cases.

Asthma↗

Reference-based pricing of prescription drugs: exploring the equivalence of angiotensin-converting-enzyme inhibitors.

BACKGROUND: Reference-based pricing is a cost-containment policy applied to prescription drugs that are in the same class and deemed to be therapeutically equivalent. Recent reference-based pricing measures have targeted several drug classes, including angiotensin-converting-enzyme (ACE) inhibitors. The objective of this study was to assess whether patients treated for hypertension with various ACE inhibitors differed in their utilization of health care services and hence, whether the various ACE inhibitors should be considered therapeutically equivalent. METHODS: A retrospective cohort was formed from 4709 Saskatchewan residents aged 40-79 years who initiated treatment for hypertension with 1 of the 3 most frequently prescribed ACE inhibitors (captopril, enalapril or lisinopril) between Jan. 1, 1991, and Dec. 31, 1993. Information obtained from universal insurance databases included prescription drug use, the number of visits to a general practitioner (GP) or specialist and the number of hospital admissions during the year before treatment was initiated and during a follow-up period of up to 4 years. Rates were statistically adjusted for potential confounding variables and compared across treatment groups. RESULTS: Of the 4709 patients, 529 were prescribed captopril initially, 2939 enalapril and 1241 lisinopril. After treatment was initiated patients prescribed captopril were dispensed more medications on average, with an overall rate of 18.6 prescriptions per patient per year (v. 16.4 and 14.7 for enalapril and lisinopril users respectively); they were admitted to hospital more often, and they made more visits to GPs and specialists. The adjusted rate ratio of the number of visits to a GP for patients receiving enalapril, relative to captopril, was 0.84 (95% confidence interval [CI] 0.80-0.88), and for those receiving lisinopril it was 0.79 (95% CI 0.74-0.83). The adjusted rate ratios for the number of visits to a specialist were similar but lower, and for the number of hospital admissions they were 0.82 for patients prescribed enalapril initially (95% CI 0.73-0.93) and 0.65 (95% CI 0.56-0.75) for those prescribed lisinopril. INTERPRETATION: Patients with hypertension who are initially prescribed captopril used health care services more than those initially prescribed enalapril or lisinopril. This suggests that ACE inhibitors may not be therapeutically equivalent.

Adult↗

Relative excess risk: an alternative measure of comparative risk.

The proverbial relative risk may not always be the most suitable measure to compare the risk of two exposures, since it inherently includes a background effect. An alternative comparative measure, the relative excess risk, is introduced. It applies to situations in which an "unexposed" reference group is included in addition to the two exposures under evaluation. This comparative measure is based solely on the component of risk due to the exposures, since it removes the background risk. Estimators of the relative excess risk are presented, along with formulas for the confidence intervals under cohort and case-control designs, using both crude and adjusted rate ratios. This new measure is illustrated with data from epidemiologic studies of the risks of oral contraceptives and antidiabetic drugs.

Accidents, Traffic↗