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Biomedical subjects

M Abrahamowicz

Publications and source records attributed to M Abrahamowicz.

At least 73 records · Page 4Linked to original sources

Small changes in outpatients lupus activity are better detected by clinical instruments than by laboratory tests.

OBJECTIVE: To evaluate and compare responsiveness of laboratory and clinical measures over 4 months in outpatient systemic lupus erythematosus (SLE). METHODS: We studied 23 patients with SLE at monthly intervals during 4 mo and collected demographic data, prednisone dose, global patient and physician assessment of disease activity on 10 cm visual analog scales (VAS), scores on 3 clinical measures of lupus disease activity [SLE disease activity index (SLEDAI), SLE activity measure (SLAM), lupus activity index (LAI)], and results of 5 routine laboratory tests [erythrocyte sedimentation rate (ESR), anti-dsDNA, C3, C4, circulating immune complexes]. We calculated correlations between a particular measure and our gold standard (physician's VAS) for individual patients and pooled this information using a novel application of the meta-analytic approach. RESULTS: The range of disease activity by patient and physician VAS varied from inactive to moderately active> Change in patient global assessment and all 3 clinical measures showed significant positive correlations with change in physician VAS (p < 0.05). Change in ESR, anti-dsDNA, or level of C3, C4, or circulating immune complexes did not correlate with change in physician VAS. CONCLUSION: Clinical measures of disease activity in SLE are more responsive to small changes than traditional laboratory tests. All 3 clinical measures appeared to perform equally well. At least one SLE disease activity measure should be used in SLE trials. The new analytic method will likely be of value in similar evaluations of responsiveness in other diseases.

Adult↗

Life expectancy following dietary modification or smoking cessation. Estimating the benefits of a prudent lifestyle.

OBJECTIVE: To evaluate the maximum benefits of dietary modification or smoking cessation to the life expectancy of North American adults. DESIGN: Using a computer model, we estimated the change in life expectancy for men and women following risk factor modification. We then estimated the total number of adults who would be targeted by national guidelines and the total person-years of life that would be saved. PATIENTS: Men and women aged 30 to 74 years who were free of coronary heart disease. INTERVENTIONS: Smoking cessation or serum cholesterol-reducing diets with 8% to 10% saturated fat and 240 to 300 mg of daily cholesterol, respectively. RESULTS: On average, dietary modification would reduce serum cholesterol levels from 0.45 mmol/L (17.4 mg/dL) to 0.75 mmol/L (29.1 mg/dL) in men and 0.12 mmol/L (4.6 mg/dL) to 0.55 mmol/L (21.4 mg/dL) in women, thereby increasing life expectancy by 0.03 to 0.4 year and 0.01 to 0.16 year, respectively. Smoking cessation would increase life expectancy from 2.59 to 4.43 years among men and from 2.6 to 3.68 years among women. Among adult Canadians, dietary modification would save 373,000 to 683,000 person-years of life. The majority of these benefits would occur among men who start dieting at ages 30 to 59 years. Smoking cessation would add more than 4 million person-years of life to the Canadian population. The relative impact of either intervention among American adults would be similar to these Canadian estimates. CONCLUSIONS: Younger men, aged 30 to 59 years, might live slightly longer after dietary change, but among women and older men the average benefits would be negligible. The benefits of smoking cessation are more uniform across age and sex and are substantially greater than those predicted for dietary change.

Adult↗

Questionable prescribing for elderly patients in Quebec.

OBJECTIVE: To estimate the prevalence of questionable and rational high-risk prescribing among elderly people of the three drug groups most commonly implicated in drug-related illness: cardiovascular drugs, psychotropic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN: Retrospective prevalence study; all prescription and billing records for the period Jan. 1 to Dec. 31, 1990, for the study sample were retrieved from the relevant provincial databases of the Régie de l'assurance-maladie du Québec. SETTING: Quebec. PARTICIPANTS: Regionally stratified random sample of 63,268 elderly medicare registrants who made at least one visit to physician in 1990 and were not living in a health care institution for the entire year. MAIN OUTCOME MEASURE: Prescription information was examined for three types of high-risk prescribing: rational and questionable drug combinations, excessive treatment duration and drugs relatively contraindicated for use in elderly people. RESULTS: Overall, 52.6% of the patients experienced one or more events of high-risk prescribing, and 45.6% experienced at least one that was questionable. High-risk prescribing was most prevalent for psychotropic drugs, and questionable prescribing was more frequent than rational prescribing in this drug group. An estimated 30.8% of the total elderly population in Quebec received benzodiazepines for more than 30 consecutive days, 12.9% received a long-acting benzodiazepine, and 13.0% received a questionable high-risk psychotropic drug combination. The prevalence of high-risk prescribing was higher among the women than among the men and increased with age until 75 to 84 years. There were significant unexplained differences between regions in the regional prevalence of high-risk prescribing, particularly of psychotropic drugs. CONCLUSION: The prevalence of questionable high-risk prescribing, especially of psychotropic drugs, is substantial among elderly people. This may be a potentially important and avoidable risk factor for drug-related illness in elderly people.

Age Factors↗

The time-dependence of long-term prediction in lupus nephritis.

OBJECTIVE: To assess the clinical, laboratory, and renal biopsy predictors of long-term outcome in lupus nephritis and to investigate the time-dependence of these predictors. METHODS: Eighty-seven lupus nephritis patients were studied retrospectively for the outcomes renal failure and fatality due to renal involvement. In addition to a conventional Cox model analysis, a new generalized time-dependent analytic approach was developed and used to assess the time-dependence of a predictor variable's importance. RESULTS: The mean followup time was 11.9 years. Renal failure (n = 19) was significantly predicted by measures of renal function (abnormal serum creatinine levels, proteinuria, duration of prior renal disease) and immunologic activity (elevated DNA binding, hypocomplementemia, and thrombocytopenia), by overall lupus disease activity measures (le Riche index, Lupus Activity Criteria Count), and by the activity index, the tubulointerstitial index, and the amount of subepithelial deposits on renal biopsy. In general, the laboratory predictors were significantly better prognostic markers in the early years after biopsy, the disease activity measures were best in the later years, and the biopsy variables were significant predictors over the entire observation period. In contrast to the renal failure outcome, the best predictors for death not directly related to lupus nephritis (n = 17) were the extent of comorbid diseases (principally vascular diseases), older age, and the chronicity index. All three predicted well over the extended observation period. CONCLUSION: The major predictor variables for renal outcomes and nonrenal outcomes are distinct. The time-dependence of the predictive ability of some variables may be important in managing individual patients. The new generalized time-dependent analytic technique may have widespread application in studies to identify prognostic factors for established disease or risk factors for the development of disease.

Adolescent↗

Quantitative sweat testing using acetylcholine for direct and axon reflex mediated stimulation with silicone mold recording; controls versus neuropathic diabetics.

Sweat glands were stimulated by iontophoresed acetylcholine (ACh). Using a two-chamber capsule, one group of sweat glands was stimulated directly by ACh, and another stimulated indirectly via axon reflexes. Sweat droplets were recorded with a silicone mold and counted by a dissecting microscope and a computerized scanner. Responses from 32 diabetics with generalized somatic peripheral neuropathy were compared with 32 controls. Counting sweat droplets by computerized scanning was more accurate than by microscope. The numbers of droplets, their total areas, and mean areas were all larger in the direct response. Counts of droplet numbers was more diagnostically useful than measuring the total area and the mean areas of the droplets. There was a high correlation between droplet numbers of the direct and the indirect sweat responses. Droplet number counts of the direct response had a slightly higher diagnostic yield than those of the technically more complicated indirect response: for a specificity of 95%, the direct response had a sensitivity of 55%, the indirect being 50%.

Acetylcholine↗

The feasibility and value of using patient satisfaction ratings to evaluate internal medicine residents.

OBJECTIVE: To determine the feasibility and value of using patient satisfaction ratings to evaluate the physician-patient relationship skills of medical residents. DESIGN: A cross-sectional survey was used to collect patient satisfaction information for medical residents from all patients attending the out-patient teaching clinics over a three-month period. The feasibility of patient rating was assessed by evaluating the reliability of resident satisfaction scores and potential sources of bias in rating. The value of using this method was assessed by evaluating the proportion of variance in ratings attributable to residents, the prevalence of residents with ratings substantially below average, and the effect of training on patient satisfaction. SETTING: The medical clinics of two teaching hospitals at McGill University. PARTICIPANTS: 91 medical residents and clinical clerks, 1,003 patients, and 1,219 visit ratings. RESULTS: An average of 12.2 satisfaction ratings were collected per resident, providing a reliability of 0.56 (intraclass correlation) for resident satisfaction score. Adjustment for differences in patient populations would be necessary to obtain comparable scores among residents. Fifteen percent of the residents had a substantially greater proportion of poor and fair satisfaction ratings than the study average. Residents were responsible for a substantial proportion of the variance in clinic waiting time and patient satisfaction rating. Training appeared to have no effect on improving satisfaction scores, except among women residents. CONCLUSIONS: Patient satisfaction ratings provide valuable information about a resident's ability to establish an effective physician-patient relationship. However, the number of ratings required to obtain a reliable estimate of resident skill may limit the feasibility of using patient ratings as part of residency evaluation.

Adolescent↗

Randomized discontinuation trials: utility and efficiency.

The randomized discontinuation trial (RDT) is a two-phase trial. In phase I all patients are openly treated with the medication being evaluated. In phase II, those who have responded are randomly assigned to continue the same treatment or switch to placebo. Usually, non-compliers and "adverse reactors" identified in phase I are excluded from phase II. To investigate the value of this design, we reviewed the advantages and limitations of discontinuation studies, and compared the RDT design to the classic randomized clinical trial design in terms of clinical utility and efficiency (sample size). A computer model was used to study the efficiency of the two designs under a broad range of assumptions. The RDT design is particularly useful in studying the effect of long-term, non-curative therapies, especially when the clinically important effect is relatively small, and the use of placebo should be minimized for ethical or feasibility reasons. However, its use is limited if the objective of an investigation is to estimate the magnitude of absolute treatment effects and toxic effects in the source population, or to evaluate a potentially curative treatment. Our results indicate that selecting responders prior to randomization has a very strong effect on the relative efficiency of the trial. Further improvement may be achieved by excluding non-compliers and adverse reactors. Under the assumptions tested in our model, the sample size required in phase II of an RDT was only 20-50% of that in a classic trial.

Computer Simulation↗

Clinical tutor evaluation: a 5-year study by students on an in-patient service and residents in an ambulatory care clinic.

Medical students on an in-patient service and residents working in an ambulatory care clinic have regularly evaluated their clinical tutors over the 5 years 1985-1989. Both groups of raters reliably and predictably evaluated their tutors and both emphasize between-tutor comparisons more than actual rating values for individual tutors. Tutors active in both contexts regularly receive higher ratings from the medical students than from the residents. Mid-course feedback to tutors in the medical course had no impact on end-of-course ratings. In neither context did tutor ratings improve from one evaluation to the next. Both groups reliably discriminate between the teaching skills and the personality traits of individual tutors.

Ambulatory Care↗

A method of dynamic analysis of iodine-123-metaiodobenzylguanidine scintigrams in cardiac mechanical overload hypertrophy and failure.

Cardiac sympathetic neuronal degeneration accompanies mechanical overload heart failure. We hypothesized that sympathetic nerve and myocyte failure share a common etiology and that 123I-metaiodobenzylguanidine (MIBG) might provide a precise method of detecting failure in chronic mechanical overload. Our aim was to develop a method for the dynamic analysis of 123I-MIBG scintigrams which could yield a quantitative index of myocardial sympathetic neuronal function in this condition. We performed serial 123I-MIBG scintigraphy in 33 volunteers, 10 orthotopic cardiac transplant recipients and 26 patients with chronic mechanical overload of the left ventricle. We constructed a compartmental model in which total heart activity represents the sum of cardiac sympathetic vesicular and cytosolic pools. Patients with antecedent mechanical overload heart failure or myocardial dysfunction had accelerated myocardial egress of tracer that we ascribed to a specific impairment in vesicular storage rather than to a more rapid turnover of an intact vesicular pool.

3-Iodobenzylguanidine↗

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↗

Effects of sodium pentobarbital anesthesia on blood flow in skin, myocutaneous, and fasciocutaneous flaps in swine.

Drug effect on flap blood flow is most commonly determined in anesthetized animals, yet the effect of the anesthetic is often poorly understood. Halothane and nitrous oxide cause profound changes in skin blood flow and thus provide an unsuitable anesthetic technique for use in measuring drug effects on skin and myocutaneous flaps in swine. The goal of this study was to determine the effects of sodium pentobarbital anesthesia on cardiovascular parameters and blood flow in skin, myocutaneous, and fasciocutaneous flaps in pigs. In seven pigs, 7 forelimb skin flaps, 7 forelimb fasciocutaneous flaps, 14 arterial buttock flaps, and 14 latissimus dorsi flaps were created. Blood flow was measured at 2-cm intervals along each flap while the animal was awake and anesthetized. A cardiac depressant effect of pentobarbital was observed, but no change in blood flow could be demonstrated in control skin or control muscle. However, pentobarbital did significantly increase blood flow in all viable portions of arterial and random skin flaps, fasciocutaneous flaps, and the cutaneous segments of the latissimus dorsi flap. These demonstrated effects of pentobarbital should be taken into consideration in designing and analyzing studies of flap blood flow in the acute postoperative phase.

Analysis of Variance↗

Adverse events associated with prescription drug cost-sharing among poor and elderly persons.

CONTEXT: Rising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada. Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups. OBJECTIVES: To determine (1) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and (2) rates of emergency department (ED) visits and serious adverse events associated with reductions in drug use before and after policy implementation. DESIGN AND SETTING: Interrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996. Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events. PARTICIPANTS: A random sample of 93 950 elderly persons and 55 333 adult welfare medication recipients. MAIN OUTCOME MEASURES: Mean daily number of essential and less essential drugs used per month, ED visits, and serious adverse events (hospitalization, nursing home admission, and mortality) before and after policy introduction. RESULTS: After cost-sharing was introduced, use of essential drugs decreased by 9.12% (95% confidence interval [CI], 8.7%-9.6%) in elderly persons and by 14.42% (95% CI, 13.3%-15.6%) in welfare recipients; use of less essential drugs decreased by 15.14% (95% CI, 14.4%-15.9%) and 22.39% (95% CI, 20.9%-23.9%), respectively. The rate (per 10 000 person-months) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons (a net increase of 6.8 [95% CI, 5.6-8.0]) and from 14.7 to 27.6 in welfare recipients (a net increase of 12.9 [95% CI, 10.2-15.5]). Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 (95% CI, 8.5-19.9) per 10 000 person-months in elderly persons (prepolicy control cohort, 32.9; postpolicy cohort, 47.1) and by 54.2 (95% CI, 33.5-74.8) among welfare recipients (prepolicy control cohort, 69.6; postpolicy cohort, 123.8). These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs. Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits. CONCLUSIONS: In our study, increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions.

Adult↗

Can computerized risk profiles help patients improve their coronary risk? The results of the Coronary Health Assessment Study (CHAS).

BACKGROUND: The Coronary Health Assessment Study (CHAS) was developed to determine the feasibility of using patient-specific, multifactorial computerized coronary risk profiles as a clinical decision aid to support primary prevention of CHD. METHODS: Study participants included 253 community based physicians, randomized into profile and control groups, and 958 of their patients. The profile group physicians received coronary risk profiles for their patients within 10 working days after the baseline patient assessment providing early feedback. The control group received their profiles only if the patient was clinically reevaluated during a 3-month follow-up visit. Patients' coronary risk factors were evaluated at baseline and at follow-up. RESULTS: The profile group had a significantly higher (P < 0.05) ratio of high-risk/low-risk patients who returned for a follow-up visit compared to the control group (1.23 vs 0.77). The patients in the profile group also had significantly (P < 0.05) greater mean reductions in total cholesterol (-0.5 vs -0.1 mmol/L), LDL cholesterol (-0.4 vs 0.0 mmol/L), the total cholesterol/ HDL ratio (-0.6 vs -0.2), and the predicted 8-year coronary risk (-1.8 vs -0.3%). CONCLUSIONS: Computer-generated coronary risk profiles can be effective in assisting physicians to identify high-risk patients. Their use is also associated with significantly greater improvements in the serum lipid profiles and the overall coronary risk of these patients.

Adult↗

Reanalysis of the Harvard Six Cities Study, part I: validation and replication.

Because the results of the Harvard Six Cities Study played a critical role in the establishment of the current U.S. ambient air quality objective for fine particles (PM(2.5)), the U.S. Environmental Protection Agency, industry, and nongovernmental organizations called for an independent reanalysis of this study to validate the original findings reported by Dockery and colleagues in the New England Journal of Medicine (vol. 329, pp. 1753-1759) in 1993. Validation of the original findings was accomplished by a detailed statistical audit and replication of original results. With the exception of occupational exposure to dust (14 discrepancies of 249 questionnaires located for evaluation) and fumes (15/249), date of death (2/250), and cause of death (2/250), the audit identified no discrepancies between the original questionnaires and death certificates in the audit sample and the analytic file used by the original investigators. The data quality audit identified a computer programming problem that had resulted in early censorship in 5 of the 6 cities, which resulted in the loss of approximately 1% of the reported person-years of follow-up; the reanalysis team updated the Six Cities cohort to include the missing person-years of observation, resulting in the addition of 928 person-years of observation and 14 deaths. The reanalysis team was able to reproduce virtually all of the original numerical results, including the 26% increase in all-cause mortality in the most polluted city (Stubenville, OH) as compared to the least polluted city (Portage, WI). The audit and validation of the Harvard Six Cities Study conducted by the reanalysis team generally confirmed the quality of the data and the numerical results reported by the original investigators. The discrepancies noted during the audit were not of epidemiologic importance, and did not substantively alter the original risk estimates associated with particulate air pollution, nor the main conclusions reached by the original investigators.

Air Pollutants↗

Reanalysis of the Harvard Six Cities Study, part II: sensitivity analysis.

Following the validation and replication of the Harvard Six Cities Study (Krewski et al., this issue), we conducted a wide range of sensitivity analyses to explore the observed associations between long-term exposure to fine particle or sulfate air pollution and mortality. We examined the impact of alternative risk models on estimates of risk, taking into account covariates not included in the original analyses. These risk models provided a basis for identifying covariates that may confound or modify the association between fine particle or sulfate air pollution and mortality, and for identifying sensitive population subgroups. The possibility of confounding due to occupational exposures was also investigated. Residence histories were coded for the study subjects and were used to examine temporal patterns of exposure and risk. Our sensitivity analyses showed the mortality risk estimates for fine particle and sulfate air pollution to be highly robust against alternative risk models of the Cox proportional hazards family, including models with additional covariates from the original questionnaires not included in the original published analyses. There was limited evidence of departures from the proportional hazards assumption. Flexible exposure-response models provided some evidence of departures from linearity at both low and high sulfate concentrations. Incorporating information on changes over time in cigarette smoking and body mass index had little effect on the association between fine particles and mortality. There was limited evidence of variation in risk with attained age, gender, smoking status, occupational exposure to dust and fumes, marital status, heart or lung diseases, or lung function. However, air pollution risk did appear to decreasing with increasing educational attainment. Extensive adjustment for occupation using aggregate indices of occupational "dirtiness" and occupational exposure to known lung carcinogens had little impact on the mortality risks associated with particulate air pollution. Our evaluation of population mobility indicated that relatively few subjects moved from their original city of residence. Attempts to identify critical exposure time windows were limited by the lack of marked interindividual variation in temporal exposure patterns throughout the study period. Overall, this extensive sensitivity analysis both supported the conclusions reached by the original investigators and demonstrated the robustness of these conclusions to alternative analytic approaches.

Age Factors↗

Increasing referral of at-risk travelers to travel health clinics: evaluation of a health promotion intervention targeted to travel agents.

BACKGROUND: Increases in travel-related illness require new partnerships to ensure travelers are prepared for health risks abroad. The travel agent is one such partner and efforts to encourage travel agents to refer at-risk travelers to travel health clinics may help in reducing travel-attributable morbidity. METHODS: A health promotion intervention encouraging travel agents to refer at-risk travelers to travel health clinics was evaluated. Information on the knowledge, attitudes, and behaviors of travel agents before and after the intervention was compared using two self-administered questionnaires. The Wilcoxon signed rank test was used to compare the mean difference in overall scores to evaluate the overall impact of the intervention and also subscores for each of the behavioral construct groupings (attitudes, barriers, intent, and subjective norms). Multiple regression techniques were used to evaluate which travel agent characteristics were independently associated with a stronger effect of the intervention. RESULTS: A small improvement in travel agents overall attitudes and beliefs (p =.03) was found, in particular their intention to refer (p =.01). Sixty-five percent of travel agents self-reported an increase in referral behavior; owners or managers of the agency were significantly more likely to do so than other travel agents (OR = 7.25; 95% CI: 1.64 32.06). Older travel agents, those that worked longer hours and those with some past referral experience, had significantly higher post-intervention scores. CONCLUSIONS: Travel agents can be willing partners in referral, and agencies should be encouraged to develop specific referral policies. Future research may be directed toward investigating the role of health education in certification curricula, the effectiveness of different types of health promotion interventions, including Internet-facilitated interventions, and the direct impact that such interventions would have on travelers attending travel health clinics.

Adult↗