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Biomedical subjects

Sebastian Schneeweiss

Publications and source records attributed to Sebastian Schneeweiss.

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

Angiotensin inhibition after myocardial infarction: does drug class matter?

BACKGROUND: Angiotensin converting enzyme-inhibitors (ACEI) and angiotensin-II-receptor blockers (ARB) are equally efficacious in reducing mortality after MI, although the latter are far more costly. Little is known about their relative use after MI in typical care settings, and about their relative effectiveness outside the clinical trial setting. OBJECTIVES: To assess temporal trends in the relative use of ACEI and ARB after myocardial infarction, and to test for differences in 1-year survival between users of these drug classes. DESIGN: Retrospective closed cohort study. PATIENTS: Medicare beneficiaries who survived >90 days after myocardial infarction, had full prescription drug coverage, and who filled a prescription for either ACEI or ARB within 90 days of myocardial infarction. MEASUREMENTS: Relative use of ACEI versus ARB over time. Adjusted relative 1-year mortality between ACEI and ARB users. RESULTS: Between 1995 and 2004, 14,190 patients met inclusion criteria. Mean age was 80 years, 75% were female, and 90% were white. Overall, 88% received an ACEI, and 12% an ARB, with the proportion receiving an ARB increasing from 2% (1995) to 25% (2004; P<.001). Multivariate-adjusted 1-year mortality did not differ between ARB and ACEI users (HR: 1.04; 95% confidence interval: 0.88 to 1.22). The findings were similar for new users of ACEI/ARB, and for those with preexisting heart failure. CONCLUSIONS: ARB users had the same 1-year mortality after myocardial infarction as ACEI users in routine care. Use of more costly ARB has increased dramatically over time, to a quarter of ACEI/ARB users, despite the lack of a therapeutic advantage for most patients.

Aged↗
PubMed2006

Indications for propensity scores and review of their use in pharmacoepidemiology.

Use of propensity scores to identify and control for confounding in observational studies that relate medications to outcomes has increased substantially in recent years. However, it remains unclear whether, and if so when, use of propensity scores provides estimates of drug effects that are less biased than those obtained from conventional multivariate models. In the great majority of published studies that have used both approaches, estimated effects from propensity score and regression methods have been similar. Simulation studies further suggest comparable performance of the two approaches in many settings. We discuss five reasons that favour use of propensity scores: the value of focus on indications for drug use; optimal matching strategies from alternative designs; improved control of confounding with scarce outcomes; ability to identify interactions between propensity of treatment and drug effects on outcomes; and correction for unobserved confounders via propensity score calibration. We describe alternative approaches to estimate and implement propensity scores and the limitations of the C-statistic for evaluation. Use of propensity scores will not correct biases from unmeasured confounders, but can aid in understanding determinants of drug use and lead to improved estimates of drug effects in some settings.

Bias↗
PubMed2006

Measuring prescribing improvements in pragmatic trials of educational tools for general practitioners.

Randomized pragmatic trials of drugs, physician education and drug policies are needed to improve pharmacosurveillance and cost-effectiveness of prescribing. Since 1994, we have developed and tested methods for low-cost education and policy trials to improve prescribing in primary care in Canada. We review methodology for using drug claims and other health services data to evaluate prescribing improvement programs and policies. We apply the lessons to a proposed trial of physician education tools (PET) for quality improvement of prescribing. Design issues for the trial include defining the potential programme in causal terms using counterfactuals, narrowing the denominator to the population affected, excluding noise from the numerator, calculating the prescribing preference, adjusting for baseline differences, controlling for modifiers and confounders, accounting for uncertainty when measuring impacts, and grouping practices for feedback and recognition. Data from a randomized trial of academic detailing illustrate measurement challenges. A decade of progress on methods for evaluating prescribing improvement programs with drug claims data has enabled planning of routine randomized pragmatic trials of education and policies in primary care in Canada.

Antihypertensive Agents↗
PubMed2006

Initiation of acetylcholinesterase inhibitors and complications of chronic airways disorders in elderly patients.

BACKGROUND AND OBJECTIVE: Acetylcholinesterase inhibitors (AChEIs), commonly prescribed in Alzheimer's disease, may trigger complications of chronic airways disorders. The aim of this study was to determine whether initiation of therapy with AChEIs contributes to complications of chronic airways disorders in an elderly population. METHODS: Sequence-symmetry analysis was used to assess two cohorts of patients, both with a history of chronic airways disorders. Both cohorts comprised Medicare beneficiaries who received drug coverage through the Pennsylvania Pharmaceutical Assistance Contract for the Elderly, between 1997 and 2002. One cohort of 922 patients initiated treatment with an AChEI; the other cohort of 2819 patients initiated treatment with a beta-adrenoceptor antagonist (beta-blocker), a comparator drug also contraindicated in chronic airways disorders. The occurrence of the following four outcomes in claims data was assessed: (i) emergency room visits for complications of chronic airways disorders; (ii) hospitalisations for complications of chronic airways disorders; (iii) physician visits for complications of chronic airways disorders; and (iv) dispensing of an antibacterial and an oral corticosteroid on the same day. Rate ratios (RRs) were adjusted for age, sex, race, nursing home residence, cognitive status, severity of chronic airways disorders, comorbid illnesses and all other patient characteristics that can be assumed to remain constant over the study period. RESULTS: Initiators of AChEIs had no detectable increased rate of complications of chronic airways disorders. Adjusted RRs of the four outcomes ranged from 1.00 (95% CI 0.61, 1.62; p = 0.99) for physician visits to 1.64 (95% CI 0.55, 4.89; p = 0.37) for emergency room visits, none reaching statistical significance. In contrast, beta-blocker initiators had significantly increased rates of all four outcomes after treatment, with adjusted RRs ranging from 1.97 (95% CI 1.18, 3.29; p = 0.009) for emergency room visits to 2.76 (95% CI 1.71, 4.45; p < 0.0001) for dispensing of an antibacterial and oral corticosteroid on the same day. CONCLUSION: These results suggest that, in current clinical practice, physicians can prescribe AChEIs safely to elderly patients with chronic airways disorders, while beta-blocker prescribing continues to result in adverse health outcomes.

Aged↗
PubMed2005

Risk of death in elderly users of conventional vs. atypical antipsychotic medications.

BACKGROUND: Recently, the Food and Drug Administration (FDA) issued an advisory stating that atypical antipsychotic medications increase mortality among elderly patients. However, the advisory did not apply to conventional antipsychotic medications; the risk of death with these older agents is not known. METHODS: We conducted a retrospective cohort study involving 22,890 patients 65 years of age or older who had drug insurance benefits in Pennsylvania and who began receiving a conventional or atypical antipsychotic medication between 1994 and 2003. Analyses of mortality rates and Cox proportional-hazards models were used to compare the risk of death within 180 days, less than 40 days, 40 to 79 days, and 80 to 180 days after the initiation of therapy with an antipsychotic medication. We controlled for potential confounding variables with the use of traditional multivariate Cox models, propensity-score adjustments, and an instrumental-variable analysis. RESULTS: Conventional antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied (< or =180 days: relative risk, 1.37; 95 percent confidence interval, 1.27 to 1.49; <40 days: relative risk, 1.56; 95 percent confidence interval, 1.37 to 1.78; 40 to 79 days: relative risk, 1.37; 95 percent confidence interval, 1.19 to 1.59; and 80 to 180 days: relative risk, 1.27; 95 percent confidence interval, 1.14 to 1.41) and in all subgroups defined according to the presence or absence of dementia or nursing home residency. The greatest increases in risk occurred soon after therapy was initiated and with higher dosages of conventional antipsychotic medications. Increased risks associated with conventional as compared with atypical antipsychotic medications persisted in confirmatory analyses performed with the use of propensity-score adjustment and instrumental-variable estimation. CONCLUSIONS: If confirmed, these results suggest that conventional antipsychotic medications are at least as likely as atypical agents to increase the risk of death among elderly persons and that conventional drugs should not be used to replace atypical agents discontinued in response to the FDA warning.

Aged↗
PubMed2005

Explained variation in a model of therapeutic decision making is partitioned across patient, physician, and clinic factors.

BACKGROUND AND OBJECTIVE: Data on therapeutic decision making have a multilevel structure that can include patient-, provider-, and facility-level variables. A statistical method is presented for attributing explained variation in patient care to different levels of aggregation in a multilevel model with the aim of prioritizing and targeting quality improvement interventions. STUDY DESIGN AND SETTING: The proposed method is used in an analysis of adherence to evidence-based guidelines for the care of patients at risk of osteoporosis. Explained variation from a multilevel model of appropriate care is partitioned across patient-, physician-, and clinic-level factors. RESULTS: The combination of patient, physician, and clinic factors explained 20.0% of the variation in patient care. Individual physician effects explained 14.0% of the variation in the data; however, more than half of this explained variation could have been attributed to the individual clinic effect. Patient fixed effects alone explained 13.4% of the variation in the observed clinical decisions. CONCLUSION: The proposed approach is an intuitive and statistically valid method for attributing explained variation in a multilevel analysis of therapeutic decision making.

Administration, Oral↗
PubMed2005

A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods.

OBJECTIVE: Propensity score (PS) analyses attempt to control for confounding in nonexperimental studies by adjusting for the likelihood that a given patient is exposed. Such analyses have been proposed to address confounding by indication, but there is little empirical evidence that they achieve better control than conventional multivariate outcome modeling. STUDY DESIGN AND METHODS: Using PubMed and Science Citation Index, we assessed the use of propensity scores over time and critically evaluated studies published through 2003. RESULTS: Use of propensity scores increased from a total of 8 reports before 1998 to 71 in 2003. Most of the 177 published studies abstracted assessed medications (N=60) or surgical interventions (N=51), mainly in cardiology and cardiac surgery (N=90). Whether PS methods or conventional outcome models were used to control for confounding had little effect on results in those studies in which such comparison was possible. Only 9 of 69 studies (13%) had an effect estimate that differed by more than 20% from that obtained with a conventional outcome model in all PS analyses presented. CONCLUSIONS: Publication of results based on propensity score methods has increased dramatically, but there is little evidence that these methods yield substantially different estimates compared with conventional multivariable methods.

Bias↗
PubMed2005

Adjusting effect estimates for unmeasured confounding with validation data using propensity score calibration.

Often, data on important confounders are not available in cohort studies. Sensitivity analyses based on the relation of single, but not multiple, unmeasured confounders with an exposure of interest in a separate validation study have been proposed. In this paper, the authors controlled for measured confounding in the main cohort using propensity scores (PS's) and addressed unmeasured confounding by estimating two additional PS's in a validation study. The "error-prone" PS exclusively used information available in the main cohort. The "gold standard" PS additionally included data on covariates available only in the validation study. Based on these two PS's in the validation study, regression calibration was applied to adjust regression coefficients. This propensity score calibration (PSC) adjusts for unmeasured confounding in cohort studies with validation data under certain, usually untestable, assumptions. The authors used PSC to assess the relation between nonsteroidal antiinflammatory drugs (NSAIDs) and 1-year mortality in a large cohort of elderly persons. "Traditional" adjustment resulted in a hazard ratio for NSAID users of 0.80 (95% confidence interval (CI): 0.77, 0.83) as compared with an unadjusted hazard ratio of 0.68 (95% CI: 0.66, 0.71). Application of PSC resulted in a more plausible hazard ratio of 1.06 (95% CI: 1.00, 1.12). Until the validity and limitations of PSC have been assessed in different settings, the method should be seen as a sensitivity analysis.

Aged↗
PubMed2005

Effects of noncardiovascular comorbidities on antihypertensive use in elderly hypertensives.

Although the benefits of antihypertensive drugs have been clearly established, they remain underused by vulnerable older populations. We examined whether the presence of noncardiovascular comorbidity deters use of antihypertensives in elderly with hypertension. We conducted a retrospective cohort study among 51,517 patients > or =65 years of age in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) Program during 1999 and 2000. All were hypertensive and had diagnoses and used treatments during 1999 to qualify for entry into 1 of the following 5 mutually exclusive cohorts: asthma/chronic obstructive pulmonary disease (COPD), depression, gastrointestinal (GI) disorders, osteoarthritis, or none of the 4 comorbidities. Proportions using antihypertensives in 2000 were assessed. Logistic regression analysis was used to identify the independent effects on antihypertensive use of the 4 comorbidities of interest, sociodemographic characteristics, other cardiovascular and noncardiovascular comorbidity, and health care utilization variables. After adjustments in multivariable analyses, antihypertensive use was consistently lower in patients with asthma/COPD (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.40 to 0.47), depression (OR, 0.50; 95% CI, 0.45 to 0.55), GI disorders (OR, 0.59; 95% CI, 0.54 to 0.64), and osteoarthritis (OR, 0.63; 95% CI, 0.59 to 0.67) relative to those without these conditions. Reduced antihypertensive use was also associated with older age, female gender, white race, more severe other comorbidities, absence of some cardiovascular indications, hospitalizations, nursing home care, physician visits, and use of fewer other medications. Highly prevalent, noncardiovascular conditions appear to deter use of antihypertensives in elderly with hypertension.

Aged↗
PubMed2005

Analytic strategies to adjust confounding using exposure propensity scores and disease risk scores: nonsteroidal antiinflammatory drugs and short-term mortality in the elderly.

Little is known about optimal application and behavior of exposure propensity scores (EPS) in small studies. In a cohort of 103,133 elderly Medicaid beneficiaries in New Jersey, the effect of nonsteroidal antiinflammatory drug use on 1-year all-cause mortality was assessed (1995-1997) based on the assumption that there is no protective effect and that the preponderance of any observed effect would be confounded. To study the comparative behavior of EPS, disease risk scores, and "conventional" disease models, the authors randomly resampled 1,000 subcohorts of 10,000, 1,000, and 500 persons. The number of variables was limited in disease models, but not EPS and disease risk scores. Estimated EPS were used to adjust for confounding by matching, inverse probability of treatment weighting, stratification, and modeling. The crude rate ratio of death was 0.68 for users of nonsteroidal antiinflammatory drugs. "Conventional" adjustment resulted in a rate ratio of 0.80 (95% confidence interval: 0.77, 0.84). The rate ratio closest to 1 (0.85) was achieved by inverse probability of treatment weighting (95% confidence interval: 0.82, 0.88). With decreasing study size, estimates remained further from the null value, which was most pronounced for inverse probability of treatment weighting (n = 500: rate ratio = 0.72, 95% confidence interval: 0.26, 1.68). In this setting, analytic strategies using EPS or disease risk scores were not generally superior to "conventional" models. Various ways to use EPS and disease risk scores behaved differently with smaller study size.

Aged↗
PubMed2005

Sudden uncontrollable somnolence and medication use in Parkinson disease.

BACKGROUND: Episodes of sudden uncontrollable somnolence have been reported in patients with Parkinson disease (PD) receiving dopamine agonists, including pramipexole and ropinirole, but controversy persists concerning their nature, severity, and frequency. OBJECTIVES: To quantify the risk of sudden uncontrollable somnolence in patients taking specific PD medications and to define its predictors. METHODS: We contacted 929 patients with PD and administered a 45- to 60-minute interview addressing medication use, adverse events, and the patient's clinical status in the preceding 6 months. Their physicians completed record reviews detailing their clinical histories and drug regimens. The outcome of interest in this case-control study was an episode of somnolence that was uncontrollable, severe, and inappropriate, such as while driving or engaged in social activity. For multiple events, the first was chosen as the index event. For each case, we sampled control time from all respondents who had no event as of the index time for that case. Multiple logistic regression was used to adjust for potential confounders. RESULTS: Episodes of uncontrollable somnolence were reported by 22% of all respondents. After controlling for age, sex, PD duration and severity, frailty, and other medication use, we found that patients receiving a dopamine agonist (pramipexole, ropinirole, or pergolide) were nearly 3-fold as likely to have episodes of sudden uncontrollable somnolence (odds ratio, 2.8; 95% confidence interval, 1.8-4.2) compared with all other PD medication users. Similar risks were seen for the 3 agents, pramipexole, ropinirole, and pergolide, each compared with levodopa alone (odds ratio, 2.2, 1.8, and 2.1, respectively), with a clear dose-response relationship for each. No increase in risk was seen with any other drugs studied. CONCLUSIONS: Dopamine agonists widely used for the management of PD significantly increase the risk of sudden uncontrollable somnolence in a dose-related manner. Greater attention to this potentially serious adverse effect will be necessary to improve the safety of use of this important category of PD drugs.

Adult↗
PubMed2005

Bone mineral density in subjects using central nervous system-active medications.

PURPOSE: Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample. SUBJECTS AND METHODS: We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index. RESULTS: In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs--benzodiazepines or antidepressants--were not associated with significantly reduced bone mineral density. CONCLUSION: In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.

Adolescent↗
PubMed2005

A Medicare database review found that physician preferences increasingly outweighed patient characteristics as determinants of first-time prescriptions for COX-2 inhibitors.

OBJECTIVE: Although innovative drugs may be underprescribed by some physicians, it is possible that rapid adoption after market introduction may lead to prescribing such drugs to patients without a clear indication. We sought to quantify the relative contributions of patient vs. physician factors to the decision to prescribe selective cyclooxygenase-2 (COX-2) inhibitors during the first 2 years of their availability. METHODS: A cohort of 37,957 Medicare beneficiaries who were enrolled in the Pharmaceutical Assistance Contract for the Elderly in Pennsylvania was identified. All patients had started using nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors between January 1, 1999, and December 31, 2000, and had no prior NSAID use. All had full prescription drug coverage, including NSAIDs and selective COX-2 inhibitors. Subsequent prescriptions were not considered. We quantified the amount of variation in first-time COX-2 prescribing that could be explained by predictors of gastrointestinal (GI) toxicity, other patient characteristics, or physician preferences. Explained variation was calculated as the R(2) (standardized to range from 0 to 1) from unconditional logistic regression and random intercept mixed effects logistic regression, fitted separately in each of eight consecutive 3-month periods. RESULTS: COX-2 inhibitors were adopted as the preferred NSAID by 55% of physicians within 180 days after they were marketed. In new NSAID users, COX-2 prescribing was twice as dependent on physician prescribing preferences (R(2)=60%) as on the combined predictors of GI toxicity (R(2)=3%) and other patient factors (R(2)=30%). The ratio of COX-2 prescribing explained by physician preferences over the contribution of patient factors increased from 2 to more than 10 over a 24-month period. CONCLUSIONS: First-time COX-2 inhibitor prescribing was somewhat dependent on patient factors in the first quarter of marketing, but the proportional influence of physician preferences increased substantially over the following 2 years, raising the question of why physician factors and not patient risk factors influence COX-2 inhibitor prescribing.

Aged↗
PubMed2005

A review of uses of health care utilization databases for epidemiologic research on therapeutics.

OBJECTIVE: Large health care utilization databases are frequently used in variety of settings to study the use and outcomes of therapeutics. Their size allows the study of infrequent events, their representativeness of routine clinical care makes it possible to study real-world effectiveness and utilization patterns, and their availability at relatively low cost without long delays makes them accessible to many researchers. However, concerns about database studies include data validity, lack of detailed clinical information, and a limited ability to control confounding. STUDY DESIGN AND SETTING: We consider the strengths, limitations, and appropriate applications of health care utilization databases in epidemiology and health services research, with particular reference to the study of medications. CONCLUSION: Progress has been made on many methodologic issues related to the use of health care utilization databases in recent years, but important areas persist and merit scrutiny.

Bias↗
PubMed2005

Identification of individuals with CKD from Medicare claims data: a validation study.

BACKGROUND: Medicare claims data might provide an efficient source for outcomes research in patients with chronic kidney disease (CKD). However, in the absence of laboratory data, one would need to identify patients with CKD from diagnosis codes associated with health care claims. The validity of this approach to identify patients with CKD has not been sufficiently studied. METHODS: From chart abstraction, we obtained the first serum creatinine measurement of 1,852 elderly Medicare beneficiaries upon hospitalization for myocardial infarction and estimated each patient's glomerular filtration rate. We then searched all Medicare claims of the preceding year for the presence of a diagnosis code for diabetic nephropathy, hypertensive nephropathy, chronic renal insufficiency, acute renal failure, and miscellaneous other renal diseases. Using the gold standard of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 (<1.00 mL/s/1.73 m2) for definition of CKD, we calculated the sensitivity, specificity, and positive and negative predictive values for each of these diagnoses and combinations of these diagnoses. RESULTS: The sensitivity of individual diagnosis algorithms ranged from 2.7% for diabetic nephropathy to 17.5% for miscellaneous. However, miscellaneous had a lower specificity (95.5%) than all other individual diagnosis algorithms (all > or =99%). Using combinations of these algorithms improved sensitivity up to 26.6%, but at the cost of lower specificity. Positive predictive values generally were high (85.7% to 97.5%), but negative predictive values were low (32.4% to 37.4%). CONCLUSION: High positive predictive values indicate that Medicare claims data can be used to accurately identify patients with CKD for study. However, the utility of such databases for comparison of patients with CKD versus lesser degrees of CKD is limited.

Aged↗
PubMed2005

Underuse of ACE inhibitors and angiotensin II receptor blockers in elderly patients with diabetes.

BACKGROUND: National guidelines recommend angiotensin-converting enzyme (ACE)-inhibitor or angiotensin receptor blocker (ARB) therapy in patients with diabetes who also have hypertension and/or proteinuria to retard the progression of renal damage. However, little is known about the adequacy of adherence to these guidelines in elderly patients with diabetes and predictors of such appropriate ACE-inhibitor or ARB use. METHODS: Using linked medical claims from Medicare and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly program, we studied a cohort of patients older than 65 years with diabetes. Baseline variables ascertained included age, sex, race, income, and several specific comorbid conditions. The outcome measure was at least 1 filled prescription for any ACE inhibitor or ARB during the quarter after the baseline year. We used multivariate logistic regression to measure predictors of use of the agents studied. RESULTS: Of 30,750 patients with diabetes studied, 21,138 patients (68.7%) also had hypertension and/or proteinuria. Of these, only 50.7% (95% confidence interval, 50.0 to 51.4) were administered an ACE inhibitor or ARB in the quarter studied. In multivariate analyses, failure to be administered either agent was associated significantly with older age, male sex, chronic lung disease, depression, dementia, and other mental illness. Greater rates of ACE-inhibitor or ARB use were found in patients with coronary artery disease or congestive heart failure. CONCLUSION: Only half the elderly patients with diabetes studied received recommended treatment with ACE inhibitors or ARBs. This shortfall could provide an opportunity for quality-improvement interventions that could result in important benefits in clinical outcomes for these high-risk patients.

Aged↗