Fenoterol and death from asthma.
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Asthma↗
Biomedical subjects
S Suissa
Publications and source records attributed to S Suissa.
The use of beta-agonists and the risk of death and near death from asthma.
BACKGROUND: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS: The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS: An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.
Administration, Inhalation↗
The benefits of treating hyperlipidemia to prevent coronary heart disease. Estimating changes in life expectancy and morbidity.
OBJECTIVE: To evaluate the lifetime benefits of reducing total serum cholesterol levels to prevent coronary heart disease (CHD). DESIGN: We developed a CHD primary prevention computer model to estimate the benefits associated with lifelong risk factor modification. We validated the model by comparing the computer estimates with the observed results of three primary CHD prevention trials. PATIENTS: Men and women age 35 to 65 years who are free of CHD, with total serum cholesterol levels ranging from 5.2 to 7.8 mmol/L (200 to 300 mg/dL), with or without additional CHD risk factors. INTERVENTIONS: Serum cholesterol reduction through dietary modification or diet and medications. MAIN OUTCOME MEASURES: Changes in life expectancy and the delay of symptomatic CHD. RESULTS: The computer forecasts for CHD end points closely matched the observed results of the Lipid Research Clinics Trial, the Helsinki Heart Study, and MRFIT. We then applied the computer model to low-risk and high-risk men and women with total serum cholesterol levels between 5.2 and 7.8 mmol/L (200 and 300 mg/dL) and estimated that, after reducing serum cholesterol levels 5% to 33%, the average life expectancy would increase by 0.03 to 3.16 years. We also forecast that the average onset of symptomatic CHD would be delayed among these patient groups by 0.06 to 4.98 years. CONCLUSION: We conclude that this computer model accurately estimates the results of clinical trials and can be used to forecast the changes in life expectancy and morbidity (the development of CHD) associated with specific CHD risk reduction interventions. The wide variation surrounding these estimates underscores the need to better define which groups of individuals will gain the most from cholesterol reduction.
Adult↗
Predicting arterial oxygenation during one-lung anaesthesia.
Eighty patients undergoing elective thoracotomy were studied to assess the possibility of predicting arterial oxygenation (PaO2) during one-lung anaesthesia (OLA). The first 50 patients were studied retrospectively. The method of multiple linear regression was used to construct a predictive equation for PaO2 during OLA. Potential predictors of PaO2 during OLA which were considered were: age, side of operation, preoperative pulmonary flow rates, preoperative and intraoperative PaO2 during two-lung ventilation. The three most significant predictors for PaO2 during OLA were: side right of operation (P < 0.05), preoperative FEV1% (P < 0.01) and intraoperative PaO2 during two-lung ventilation (P = 0.0001). The predictive equation for PaO2 after ten minutes of OLA was: PaO2 = 100 - 72 (side) - 1.86 (FEV1%) + 0.75 (two-lung) PaO2; (for side insert 0 for left-sided thoracotomy and 1 for right-sided thoracotomy). The remaining 30 patients were studied prospectively and the predicted PaO2 correlated with the observed PaO2 after ten minutes of OLA (r = 0.73, P < 0.01). Four of 30 patients had a predicted PaO2 at ten minutes of OLA < 150 mmHg. Of these, 2/4 subsequently required abandonment of OLA for pulse oximetric saturation < 85%. We conclude that although it is not possible to predict an individual patient's PaO2 during OLA with a high degree of accuracy, it is possible, before the initiation of OLA, to identify those patients whose arterial oxygenation is likely to decrease to low levels during OLA.
Aged↗
Clinical experience with a single field rotational total skin electron irradiation technique for cutaneous T-cell lymphoma.
Between October 1981 and December 1989, 44 patients with cutaneous T-cell lymphoma (CTCL) were treated with a single field rotational total skin electron irradiation (RTSEI) technique developed in the McGill University, Department of Radiation Oncology. Only 11 (25%) of the 44 patients had received no prior treatment. Three-quarters (33/44) had advanced (T3 or T4) disease. Complete responses were seen in 32/44 (73%) of patients (91% T2, 71% T3 and 58% T4), but only 3/11 (27%) of patients with T2 disease and 3/21 (14%) of patients with T3 disease remain in continuous complete remission in the skin, after median intervals of 58 and 35 months, respectively. Median cause-specific survival for the whole group is 43 months and survival at 5 years is 38%. Survival was significantly better for patients with T2 disease than for patients with T3 disease (relative risk 4.3; 95% CI 1.4-13.2) and patients with T4 disease (relative risk 3.1; 95% CI 0.8-12.1). The RTSEI technique used at McGill has depth-dose characteristics and photon contamination similar to other commonly used TSEI techniques. It is relatively simple and provides a homogenous dose distribution over the entire skin surface in a short treatment time. Results of treatment are similar to those obtained with other techniques. For T2 disease, TSEI is an effective treatment modality with a possibility of long-term tumor control. For more advanced disease, more aggressive treatment, which may include TSEI, is necessary.
Adult↗
The evolution of compensated occupational spinal injuries. A three-year follow-up study.
This study was undertaken to follow up an incidence rate study of spinal injuries carried out from a cross-sectional random sample consisting of 2,342 workers who were compensated at least once in the year 1981 by the Quebec Worker's Compensation Board (QWCB) for an absence from work. These workers were followed for 3 years using the QWCB information system to record any recurrence of compensated absence from work. A total of 850 (36.3%) had at least one recurrence, and had longer episodes of absence than those without a recurrence (P less than 0.0001). Of these 850 workers, 824 (96.9%) had less than five recurrences and showed a systematic trend of gradual increasing duration of absence on each subsequent recurrence (P less than 0.05 in a repeated measures analysis of variance). A positive relationship was found between the duration of the initial episode of absence from work and the subsequent history of absence from work, both in terms of risk of recurrence (P less than 0.001) and of cumulated absence from work (P less than 0.0001), after controlling for age, sex, and site of symptoms. The computed instantaneous risk of entering a recurrence in a 31 year-old man experiencing lumbar symptoms, was 19.9% (95% confidence interval = 19.8-19.9) in the year following an initial episode of one day duration, and 26.7% (95% confidence interval = 24.3-29.3) after an initial episode of 6 months.
Absenteeism↗
Can experienced clinicians predict the outcome of lupus nephritis?
The ability of four experienced clinicians to predict short-term outcome (serum creatinine level at 1 year) and long-term outcome (renal insufficiency) was evaluated in 87 patients with lupus nephritis. The correlational agreement and the accuracy of their predictions were contrasted with the actual outcomes observed and with statistically generated prognostic regression models. In contrast to previously published data, all four clinicians predicted both short-term outcomes (P < 0.001) and long-term outcomes (P < 0.02) well. The clinicians' predictions approximated that of a statistically generated computer model for both agreement and accuracy for renal function at 1 year. The four clinicians identified nearly identical clinical variables as important in determining prognosis. Provision of biopsy data to the clinicians improved short-term and long-term prediction slightly. The value of the statistical models was 'validated' by demonstrating that three of the four clinical variables identified by the models, but not by the clinicians, could enhance clinical prediction (P < 0.05). In addition, the extent of tubulo-interstitial involvement on biopsy, a predictor that has recently received increased attention, could improve the long-term clinical predictions of all four clinicians (P < 0.05).
Adolescent↗
Factors predicting course of beta-cell function in IDDM.
OBJECTIVE: The purpose of this study was to determine whether the severity o clinical presentation, sex, age, HLA type, and the presence of IAs and ICAs could predict the variation of residual insulin secretion as measured by the serum C-peptide response to a Sustacal meal. RESEARCH DESIGN AND METHODS: A cohort of 151 newly diagnosed IDDM children (mean age 10.2 +/- 4.6 yr) was followed prospectively for 3 yr. Thirty-five patients (12 males, 23 females) were still secreting C-peptide after 36 mo. RESULTS: We found that age (P = 0.0001), sex (P = 0.003), presence of ICA (P = 0.006), severity of clinical presentation (P = 0.001), and symptom duration (P = 0.002) significantly predicted the rate of loss of C-peptide secretion. The risks of accelerated C-peptide disappearance decreased with increasing age, the risk ratios being 0.25 for the older group (greater than 12 yr) compared with the younger group (less than 6 yr) and 0.50 for the intermediate group (6-12 yr) compared with the younger group. The risk for the presence of ICA was 1.7, and the risk for males was 1.7 also. There was a significant negative correlation between ICA titers and C-peptide at 18 and 24 mo after diagnosis (P = 0.04). There were no significant differences in HbA1 values between patients who secreted C-peptide and those who did not. CONCLUSIONS: We conclude that younger age of onset, male sex, high titers of ICA, severe clinical presentation, and shorter symptom duration significantly predict accelerated rates of loss of C-peptide secretion.
Age Factors↗
Study designs of adverse events in asthma treatment.
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Adrenergic beta-Agonists↗
The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients.
It has been previously demonstrated that serum lactate dehydrogenase is elevated among HIV patients with pneumocystis carinii pneumonia (PCP). To evaluate the clinical utility of this test we analyzed the admission LDH levels of patients hospitalized for the first time due to the secondary complications of AIDS. Among 76 patients without a prior history of PCP, 41 (54%) had PCP diagnosed during their hospitalization while 35 (46%) did not have PCP. Serum LDH was significantly higher among PCP patients than in patients without PCP (mean = 423 IU/L vs 234 IU/L). Receiver operating characteristic curve analysis demonstrated that at an optimal cutoff point of LDH greater than or equal to 240 IU/L, the test sensitivity and specificity were 0.78 and 0.74 respectively among all hospitalized patients. However, when only patients with dyspnea were considered, the optimal test sensitivity and specificity improved to 0.94 and 0.78 at a cutoff point of LDH greater than or equal to 220 IU/L. Comparing the areas under fitted ROC curves, serum LDH was a significantly better discriminator among patients with dyspnea than among those who were not short of breath. We conclude that while serum LDH is strongly associated with the presence of PCP among AIDS patients, it is a poor screening test for PCP when applied to all hospitalized AIDS patients with and without respiratory complaints. Serum LDH is no substitute for appropriate microbiological studies. However, with further evaluation, it may prove to be a useful test in guiding the clinical management of dyspneic patients in whom sputum or bronchial examinations are negative or not immediately available.
Acquired Immunodeficiency Syndrome↗
Testing various methods of introducing health charts into medical records in family medicine units.
OBJECTIVE: To test three methods of introducing health charts into the medical records of six family medicine units. DESIGN: Quasi-experiment. PARTICIPANTS: The staff physicians and family medicine residents in all six units and the nurses in two units. INTERVENTIONS: Group 1 (minimal intervention): health charts, a user's guide and one training session. Group 2 (intermediate intervention): same intervention as for group 1 plus two feedback sessions at 3 and 6 months. Group 3 (maximum intervention): same intervention as for group 2 plus promotion of the team concept (nurses were included). The intervention phase lasted from September 1987 to August 1988. OUTCOME MEASURES: The frequency with which the health charts were used, the item scores of each preventive care activity and the overall unit scores. Data were gathered through chart audits at baseline and at the end of the intervention phase. RESULTS: The frequency with which the health charts were used varied from 3.9% to 26.9%. The greatest increases in item scores were observed in the use of mammography (20.0%), counselling on lifestyle (19.4%) and breast examination (17.2%). Although the overall improvement in the unit scores was statistically significant (p less than 0.05) the hypothesis of an increasing gradient of effect across the three intervention groups could not be tested because of the variation in scores across the units. CONCLUSION: Health charts and other similar tools are useful; however, they are not sufficient to change practice behaviours. The support of a "champion" on the health care team might well be a determining factor of success for the delivery of preventive services in primary care practice.
Adult↗
Screening for hypercholesterolemia among Canadians: how much will it cost?
OBJECTIVE: To determine the cost of screening all Canadians aged 30 years or more without coronary heart disease (CHD) for hypercholesterolemia. DATA SOURCES: The expected results of initial screening of the serum cholesterol level were estimated on the basis of 1986 Canadian census data and the 1978 Canada Health Survey. The results of repeat testing were estimated on the basis of data from the Lipid Research Clinics Prevalence Study. Lipid profile results were extrapolated from tests at the Montreal General Hospital's clinical chemistry laboratory. Laboratory costs and primary care practitioner costs were provided by the Canadian Society of Clinical Chemists and provincial fee schedules respectively. MAIN RESULTS: Among 12,479,356 Canadians free of CHD 48.7% would be identified as being at high risk, 4.8% would be identified as being at moderate risk, and 46.6% would be reassured that their lipid risk for CHD was low. The total cost of implementing the program in the first year would be $432 million to $561 million ($325 million for laboratory tests and $107 million to $236 million for visits to primary care practitioners). CONCLUSION: The substantial cost of implementing a nationwide screening program must be weighed against the expected benefits to ensure that the final result is both practical and economically feasible.
Adult↗
Binary methods for continuous outcomes: a parametric alternative.
Often a "disease" or "state of disease" is defined by a subdomain of a continuous outcome variable. For example, the subdomain of diastolic blood pressure greater than 90 mmHg has been used to define hypertension. The classical method of estimating the risk (or prevalence) of such defined disease states is to dichotomize the outcome variable according to the cutoff value. The standard statistical analysis of such risk of disease then exploits methods developed specifically for binary data, usually based on the binomial distribution. We present a method, based on the assumption of a Gaussian (normal) distribution for the continuous outcome, which does not resort to dichotomization. Specifically, the estimation of risk and its variance is presented for the one- and two-sample situations, with the latter focusing on risk differences and ratios, and odds ratios. The binomial approach applied to the dichotomized data is found to be less efficient than the proposed method by 67% or less. The latter is found to be very accurate, even for small sample sizes, although rather sensitive to substitutions of the underlying distribution by thicker tailed distributions. Canadian total cholesterol data are used to illustrate the problem. For the one-sample case, the approach is illustrated using data from a study of the arterial oxygenation of 20 patients during one-lung anesthesia for thoracic surgery. For the two-sample case, data from a prognostic study of the renal function of 87 lupus nephritic patients are used.
Binomial Distribution↗
Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management.
Two recent epidemiologic case-control studies suggested that fenoterol, a selective beta-adrenergic agonist, was associated with an increase in the risk of asthma death. The results of these studies were criticized because of methodologic problems in the choice and selection of control subjects; the different methods used to gather exposure data in cases and control subjects; and because of inadequate classification and adjustment for asthma severity. In response to this controversy, a new study is underway, the Saskatchewan Asthma Epidemiology Project. The SAEP includes two complementary studies, an historic cohort and a case-control analysis, that employ the computerized databases of the Saskatchewan Health Department. A unique aspect of the SAEP is the attempt to incorporate knowledge of asthma physiology and management into the design of the studies. Specifically, the study design recognized the role of antiinflammatory drugs in asthma treatment; the distinction between asthma death and near-fatal asthma; the severity of asthma; patterns of drug use; and the distinction between inadequate clinical care and disease severity. The strategies we employed in the SAEP may prove helpful to investigators whenever clinical and biologic processes create sources of potential bias requiring special procedures for the design and analysis of epidemiologic studies.
Adolescent↗
Predictors of one year outcome in lupus nephritis: the importance of renal biopsy.
The short-term prognosis of lupus nephritis was evaluated by assessing serum creatinine 12 months after renal biopsy in 87 patients with lupus nephritis. On univariate analysis, significant clinical and laboratory predictors of this outcome included clinical signs of renal injury (serum creatinine, 24-hour urinary protein, prolonged renal disease, nephrotic syndrome, serum albumin), as well as thrombocytopenia, older age, and coexisting illness or hypertension at the time of biopsy. On renal biopsy, diffuse proliferative nephritis, higher activity, chronicity, or tubulointerstitial scores, or subendothelial or subepithelial electron dense deposits predicted a higher serum creatinine 12 months after biopsy. A clinical predictive model was developed which included as independent predictors serum creatinine, age, platelet count and 24-hour urinary protein. Any one of three biopsy variables added information to the clinical prediction model: a marked quantity of subendothelial deposits (p = 0.02), a higher activity index score (p = 0.02), or the presence of diffuse proliferative lupus nephritis (p = 0.05). However, the relative predictive accuracy of the clinical model did not improve with the addition of any of the biopsy variables. The value of renal biopsy in lupus nephritis is discussed based on the ability of biopsy information to confirm the prognosis, to add new predictive information for a group of subjects, and to improve predictive accuracy for individual patients.
Adolescent↗
The 2 x 2 matched-pairs trial: exact unconditional design and analysis.
An exact unconditional method for the design and analysis of the 2 x 2 matched-pairs trial is presented. Unlike the exact conditional method, which is based on only the number of discordant pairs, the exact unconditional method uses the total number N of sampled pairs. This unconditional test, based on a simple Z statistic, yields sample sizes that are generally smaller than those produced by the exact conditional test for the cases tabulated herein, namely one-sided alpha = .01, .025, and .05 along with 80% and 90% power. Moreover, it is found to be uniformly more powerful than the latter for all the combinations of parameters considered in this paper, namely alpha = .01, .025, and .05, and N = 10(1)200. The method is illustrated by assessing various design options of an in vitro study of the effectiveness of antimicrobial agents. Some numerical examples of matching efficiency are also given.
Biometry↗
Predicting arterial oxygenation during one-lung ventilation with continuous positive airway pressure to the nonventilated lung.
Forty patients undergoing elective thoracotomy were studied to assess the possibility of predicting PaO2 during one-lung ventilation (OLV) when continuous positive airway pressure (CPAP) was applied to the nondependent lung. The first 20 patients were studied retrospectively and the three most significant independent variables that correlated with PaO2 during OLV with CPAP were: side of operation (P = 0.04), FEV1/FVC ratio (P = 0.01), and the intraoperative PaO2 during two-lung ventilation (P = 0.0002). By the method of multiple linear regression, these three variables were used to construct a predictive equation for PaO2 during OLV with CPAP. The second 20 patients were studied prospectively and the predicted PaO2 correlated significantly with the observed PaO2 during OLV with CPAP (r = 0.86, P less than 0.001). Therefore, it is concluded that the PaO2 during OLV with CPAP can be predicted using routinely available data.
Aged↗