Biomedical subjects

Therese A Stukel

Publications and source records attributed to Therese A Stukel.

At least 19 recordsLinked to original sources

PubMed2026

Adult outcomes of clinically relevant genomic disorders: A systematic review and meta-analysis.

PURPOSE: Genomic disorders comprise a major source of human disease with survival into adulthood for most individuals, but data on adult outcomes are limited. METHODS: We conducted a formal search to identify studies of 14 clinically relevant, molecularly confirmed deletion syndromes with ≥5 adults reporting on prevalence of cardiovascular risk and other outcomes. Outcomes were pooled across deletion syndromes and by syndrome, using random-effects models. RESULTS: Of 1352 studies screened, 53 reported on nonoverlapping samples of 13 deletion syndromes. Estimated pooled prevalences, at age <30-40 for most, included 47% (95% CI 33-57%; n = 2076) for obesity, and for 10 deletion syndromes: diabetes 24% (95% CI 17-33%; n = 1739), hypertension 36% (95% CI 28-33%; n = 1314), and dyslipidemia 29% (95% CI 22-36%; n = 1127). High heterogeneity for each outcome was partly explained by a significant subgroup effect of individual syndrome. The few available mortality studies indicated premature mortality. CONCLUSION: Pooled results suggest that, although there may be elevated prevalence of adult cardiovascular risk conditions, high heterogeneity indicates caution when considering rare deletion syndromes collectively. The paucity of data extending into later adulthood and using age-matched control comparisons supports the need for prospective studies of large, well-phenotyped cohorts to inform adult penetrance of treatable medical diseases in this emerging group of young adults.

Humans↗

PubMed2007

Measures of cumulative exposure from a standardized sun exposure history questionnaire: a comparison with histologic assessment of solar skin damage.

Ultraviolet radiation exposure is the dominant environmental determinant of all major forms of skin cancer; however, the nature of the association is incompletely understood. Existing instruments to capture sun exposure history tend to yield reproducible results, but the validity of these responses is unknown. To address this question, the authors examined the relation between responses to a standardized sun exposure instrument and histologic evidence of actinic damage in a population-based study of keratinocyte cancers from New Hampshire diagnosed from July 1, 1997, through March 31, 2000. A single study dermatopathologist histologically reviewed the adjacent skin of 925 skin cancer biopsies for the presence of solar keratoses and the extent of solar elastosis. The authors compared these measures with responses to a personal interview on history of sunburns, sunbathing, and time spent outdoors. Focusing on site-specific exposure, they found variables that estimated cumulative exposure related to histologic evidence of actinic damage. In contrast, measures of acute/intermittent exposure were generally unrelated to solar damage histologically. Findings suggest that cumulative, but not intermittent, measures of sun exposure derived from a personal interview appear to reflect a person's exposure history based on histologic evidence.

Aged↗

PubMed2006

Regional differences in process of care and outcomes for older acute myocardial infarction patients in the United States and Ontario, Canada.

BACKGROUND: Previous comparisons of acute myocardial infarction (AMI) treatment between the United States and Canada are limited because they compared selected patients from randomized trials, used administrative data that lacked clinical detail, or did not consider regional differences in AMI treatment. METHODS AND RESULTS: We compared medication use, invasive cardiac procedure use, and 30-day risk-standardized mortality rates of 38,886 fee-for-service Medicare beneficiaries hospitalized with AMI in the United States and 5634 similarly aged patients in Ontario, Canada, from 1998 and 2001. Baseline characteristics and illness severity across the US regions and Ontario were not substantially different. Cardiac catheterization use in AMI patients was significantly higher in the United States compared with Ontario (38.7% versus 16.8%, P<0.001), but significant regional variations existed, in which the northeastern United States had significantly lower utilization rates (25.6%) compared with other US regions. Beta-blocker use among ideal candidates was highest in the northeastern United States (77.6% versus 69.7% in the United States as a whole, P<0.001) and angiotensin-converting enzyme inhibitor use was highest in Ontario (69.1% versus 58.2% in the United States, P<0.001). Risk-standardized mortality rates at 30 days were not substantially different across the regions. CONCLUSIONS: Previous studies have suggested a clear divergence in invasive cardiac therapy for AMI patients between the United States and Canada on the basis of health care financing and structural differences. Our findings of similar treatment patterns in the northeastern United States and Ontario suggest that regional practices may have a greater impact on treatment patterns than the respective health care delivery systems.

Aged↗

PubMed2006

Guillain-Barré syndrome after influenza vaccination in adults: a population-based study.

BACKGROUND: Whether influenza vaccination is associated with Guillain-Barré syndrome (GBS) remains uncertain. METHODS: We conducted 2 studies using population-based health care data from the province of Ontario, Canada. In the first study, we used the self-matched case-series method to explore the temporal association between probable influenza vaccination (adults vaccinated during October and November) and subsequent hospitalization because of GBS. In the second study, we used time-series analysis to determine whether the institution of a universal influenza immunization program in October 2000 was associated with a subsequent increase in hospital admissions because of GBS at the population level. RESULTS: From April 1, 1992, to March 31, 2004, we identified 1601 incident hospital admissions because of GBS in Ontario. In 269 patients, GBS was diagnosed within 43 weeks of vaccination against influenza. The estimated relative incidence of GBS during the primary risk interval (weeks 2 through 7) compared with the control interval (weeks 20 through 43) was 1.45 (95% confidence interval, 1.05-1.99; P = .02). This association persisted in several sensitivity analyses using risk and control intervals of different durations. However, a separate time-series analysis demonstrated no evidence of seasonality and revealed no statistically significant increase in hospital admissions because of GBS after the introduction of the universal influenza immunization program. CONCLUSION: Influenza vaccination is associated with a small but significantly increased risk for hospitalization because of GBS.

Adult↗

PubMed2006

Effect of NSAIDs on the recurrence of nonmelanoma skin cancer.

Experimental studies have consistently shown a protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) against nonmelanoma skin cancers (NMSC). However, little human epidemiological research has been done in this regard. We used data from the Skin Cancer Chemoprevention Study to explore the association of NSAID use and with the risk of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). 1,805 subjects with a recent history of NMSC were randomized to placebo or 50 mg of daily beta-carotene. Participants were asked about their use of over-the-counter and prescription medications at baseline and every 4 months during the trial. Skin follow-up examinations were scheduled annually with a study dermatologist; confirmed lesions were the endpoints in the study. We used a risk set approach to the analysis of grouped times survival data and unconditional logistic regression to compute odds ratios [ORs] for various exposures to NSAIDs. The use of NSAIDs was reported in over 50% of questionnaires. For BCC, NSAIDs exhibited a weak protective effect in crude analyses, which attenuated markedly after adjustment. For SCC, the use of NSAIDs in the year previous to diagnosis reduced the odds by almost 30% (adjusted OR=0.71, 95% CI 0.48-1.04). When we accounted for frequency of use, results for BCC were not striking, and there were inconsistent suggestions of an inverse association with SCC. There were some indications of a modest, nonsignificant reduction on the number of BCCs and SCCs with NSAID use. Our data suggest a weak and inconsistent chemopreventive effect of NSAIDs on BCC and SCC.

Aged↗

PubMed2006

Surge capacity associated with restrictions on nonurgent hospital utilization and expected admissions during an influenza pandemic: lessons from the Toronto severe acute respiratory syndrome outbreak.

BACKGROUND: Current influenza pandemic models predict a surge in influenza-related hospitalizations in affected jurisdictions. One proposed strategy to increase hospital surge capacity is to restrict elective hospitalizations, yet the degree to which this measure would meet the anticipated is unknown. OBJECTIVES: To compare the reduction in hospitalizations resulting from widespread nonurgent hospital admission restrictions during the Toronto severe acute respiratory syndrome (SARS) outbreak with the expected increase in admissions resulting from an influenza pandemic in Toronto. METHODS: The authors compared the expected influenza-related hospitalizations in the first eight weeks of a mild, moderate, or severe pandemic with the actual reduction in the number of hospital admissions in Toronto, Ontario, during the first eight weeks of the SARS-related restrictions. RESULTS: Influenza modeling for Toronto predicts that there will be 4,819, 8,032, or 11,245 influenza-related admissions in the first eight weeks of a mild, moderate, or severe pandemic, respectively. In the first eight weeks of SARS-related hospital admission restrictions, there were 3,654 fewer hospitalizations than expected in Toronto, representing a modest 12% decrease in the overall admission rate (a reduction of 1.40 admissions per 1,000 population). Therefore, influenza-related admissions could exceed the reduction in admissions resulting from restricted hospital utilization by 1,165 to 7,591 patient admissions, depending on pandemic severity, which corresponds to an excess of 0.44 to 2.91 influenza-related admissions per 1,000 population per eight weeks, and an increase of 4% to 25% in the overall number of admissions, when compared with nonpandemic conditions. CONCLUSIONS: Pandemic modeling for Toronto suggests that influenza-related admissions would exceed the reduction in hospitalizations seen during SARS-related nonurgent hospital admission restrictions, even in a mild pandemic. Sufficient surge capacity in a pandemic will likely require the implementation of other measures, including possibly stricter implementation of hospital utilization restrictions.

Bed Occupancy↗

PubMed2006

The risk of missed diagnosis of acute myocardial infarction associated with emergency department volume.

STUDY OBJECTIVE: Missed diagnosis of acute myocardial infarction is associated with adverse clinical outcomes and more dollars recovered in malpractice suits than any other condition. The rate of missed diagnosis varies between emergency departments (EDs); we hypothesized that it is associated with the volume of acute myocardial infarction patients treated in an ED and that the association can be explained by other hospital characteristics. METHODS: We linked the records of all acute myocardial infarction patients admitted to an Ontario hospital in 2002 to 2003 to their ED visit records in the 7 days preceding admission. Acute myocardial infarctions were defined as missed if the diagnosis on the previous visit matched a list of cardiac symptoms and illnesses. We assessed whether annual volume of admitted acute myocardial infarction patients treated in the ED (grouped as 0 to 49; 50 to 99; 100 to 199; 200 to 299; and > or = 300) was associated with missed acute myocardial infarction, adjusting for age, sex, teaching hospital status, and acute myocardial infarction severity. In a secondary analysis, we used data from a survey of Ontario EDs to assess whether hospital characteristics (triage practices, use of diagnostic tests, and consultant availability) explained the volume association. RESULTS: Of 19,663 acute myocardial infarction patients, mean age (68.3 years), sex (63% men), and predicted 1-year mortality (mean 0.21; SD 0.18) were similar across volume groups. The rate of missed acute myocardial infarction was 2.1% (95% confidence interval [CI] 1.9% to 2.3%) and varied from 0% to 29% across EDs. Compared with very high-volume EDs, the adjusted odds ratio of missed acute myocardial infarction was 2.0 in very low- (95% CI 1.5 to 2.7) and 1.6 in low- (95% CI 1.1 to 2.3) volume EDs. Consultant availability partially explained the volume effect. CONCLUSION: Lower-volume EDs have up to 2-fold higher odds of missed acute myocardial infarctions compared with highest-volume ones after controlling for patient factors. Many current technologies designed to increase diagnostic sensitivity are feasible only in higher-volume centers. Efforts to reduce overall rates of missed acute myocardial infarctions should instead focus on simpler solutions appropriate for lower-volume EDs, such as telemedicine to improve access to consultant expertise.

Adult↗

PubMed2006

Volume and process of care in high-risk cancer surgery.

BACKGROUND: Although relations between procedure volume and operative mortality are well established for high-risk cancer operations, differences in clinical practice between high-volume and low-volume centers are not well understood. The current study was conducted to examine relations between hospital volume, process of care, and operative mortality in cancer surgery. METHODS: Using the Medicare claims database (2000-2002), we identified all patients undergoing major resections for lung, esophageal, gastric, liver, or pancreatic cancer (n=71,558). Preoperative, intraoperative, and postoperative processes of care potentially related to operative mortality were identified from inpatient, outpatient, and physician claims files using appropriate International Classification of Diseases--Clinical Modification (ICD-9) and Current Procedural Terminology (CPT) codes. We then assessed variation in the use of each process according to hospital volume, adjusting for patient characteristics and procedure type. Study Participants were US Medicare patients. The main outcome measure was specific processes of care. RESULTS: Relative to those at low-volume centers (lowest 20th by volume), patients at high-volume hospitals (highest 20th) were significantly more likely to undergo stress tests (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.21-1.87), but not other preoperative imaging tests. They were more likely to see medical or radiation oncologists (OR: 1.37, 95% CI: 1.16-1.62), but not other specialists, preoperatively. Although blood transfusions and use of epidural pain management did not vary significantly by volume, patients at high-volume hospitals had significantly longer operations and were more likely to receive perioperative invasive monitoring (OR: 2.56, 95% CI: 1.82-3.60). Differences in measurable processes of care did not explain volume-related differences in operative mortality to any significant degree. CONCLUSIONS: Although high-volume and low-volume hospitals differ with regard to many aspects of perioperative care, mechanisms underlying volume-outcome relations in high-risk cancer surgery remain to be identified.

Aged↗

PubMed2006

Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin.

BACKGROUND: Although infection with human papillomaviruses (HPVs) is a major risk factor for several epithelial cancers, an etiologic relationship between HPV and keratinocyte cancers, such as squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), remains unclear. METHODS: In a population-based case-control study of 252 SCC case patients, 525 BCC case patients, and 461 control subjects, we used multiplex serology to detect antibodies in plasma samples against 16 HPV types from phylogenetic genera alpha, beta, and mu. Multiplex serology is a new method that is based on fluorescent bead technology and allows simultaneous detection of antibodies against up to 100 different in situ affinity-purified recombinant HPV proteins. Data on sun sensitivity, outdoor exposure, and other risk factors for keratinocyte cancers were collected through personal interviews. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated via unconditional logistic regression models. RESULTS: Overall, we detected HPV antibodies more frequently in SCC patients than in control subjects (OR = 1.6, 95% CI = 1.2 to 2.3), but we found no difference in HPV seropositivity between BCC case patients and control subjects (OR = 0.8, 95% CI = 0.6 to 1.1). Among HPV types, seropositivity to HPV types in genus beta (OR = 1.5, 95% CI = 1.0 to 2.1), particularly HPV 5 (OR = 1.8, 95% CI = 1.0 to 3.1), was associated with SCC risk. Individuals with tumors on chronically sun exposed sites were more likely to be seropositive for beta HPV types than individuals with SCC at other anatomic sites. The highest SCC risk was associated with positivity for multiple HPV types and, among individuals seropositive for HPV beta, a tendency to sunburn; however, the associations had limited statistical precision. CONCLUSIONS: Our findings support a role for HPV types from the genus beta in the pathogenesis of SCC.

Adult↗

PubMed2006

Outpatient gatifloxacin therapy and dysglycemia in older adults.

BACKGROUND: Gatifloxacin has been associated with both hypoglycemia and hyperglycemia. We examined dysglycemia-related health outcomes associated with various antibiotics in a population of approximately 1.4 million Ontario, Canada, residents 66 years of age or older. METHODS: We conducted two population-based, nested case-control studies. In the first, case patients were persons treated in the hospital for hypoglycemia after outpatient treatment with a macrolide, a second-generation cephalosporin, or a respiratory fluoroquinolone (gatifloxacin, levofloxacin, moxifloxacin, or ciprofloxacin). In the second, case patients were persons who received hospital care for hyperglycemia. For each case patient, we identified up to five controls matched according to age, sex, the presence or absence of diabetes, and the timing of antibiotic therapy. RESULTS: Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes. CONCLUSIONS: As compared with the use of other broad-spectrum oral antibiotics, including other fluoroquinolones, the use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for both hypoglycemia and hyperglycemia.

Aged↗

PubMed2006

Proliferation of cardiac technology in Canada: a challenge to the sustainability of Medicare.

BACKGROUND: Critics remain skeptical about the long-term sustainability of Medicare in Canada because of the proliferation of health technology and escalating expenditures. The objective of this study was to examine the temporal trends in the utilization and costs of cardiovascular technologies for the evaluation and/or management of patients with ischemic heart disease in Canada. METHODS AND RESULTS: This repeated cross-sectional population-based study of Ontario residents examined the temporal trends in the utilization and costs associated with echocardiography, stress (imaging and nonimaging) testing, coronary angiography, percutaneous coronary intervention (PCI), and bypass surgery between 1992 and 2001. Annual costs increased by nearly 2-fold over the 10-year study period and cumulatively accounted for more than $2.8 billion (Canadian) in expenditures. The proliferation in use of cardiac testing/interventions over time outstripped both demographic shifts and changes in the prevalence of coronary artery disease. Annual increases were widespread for all procedures (P<0.001) and ranged from 2% per year for nonimaging stress tests to 12% per year for PCI, after adjustment for age and sex. Generally, utilization rates were higher among the elderly, males, and those of low socioeconomic status. With few exceptions, annual increases in the utilization rates of cardiac tests and procedures were disproportionately higher among the elderly and women, but they were similar across socioeconomic subgroups. Increases in utilization appeared to reflect referrals toward higher-risk populations. CONCLUSIONS: Although definitive conclusions about the appropriateness of temporal patterns cannot be ascertained, the proliferation of cardiac testing challenges the sustainability of Medicare in Canada, especially given uncertainty as to whether the accompanying incremental rise in total expenditures translates into significant outcome benefits in the population.

Adult↗

PubMed2006

Pregnancy history and incidence of melanoma in women: a pooled analysis.

There is evidence that pregnancy history including age at first birth and parity may play a role in risk of cutaneous melanoma in women, although, epidemiological findings are inconsistent. We conducted a collaborative analysis of these factors using the original data from ten completed case-control studies (2391 cases and 3199 controls), and assessed the potential confounding effects of socioeconomic, pigmentary, and sun exposure-related factors. We found no overall association with ever having a live birth (pooled odds ratio (pOR) 0.95, 95% confidence interval (CI) 0.67-1.35). However, we detected a reduced risk of melanoma among women with higher parity (> or = 5 versus no live births pOR 0.76, 95% CI 0.49-1.18, each live birth pOR 0.95, 95% CI 0.91-0.99, p trend = 0.05). Women with both earlier age at first birth (e.g., <20 years) and higher parity (e.g., > or = 5 live births) had a particularly lower risk than women with later age at first birth (e.g., > or = 25 years) and lower parity (e.g., <5 live births) (pOR 0.33, 95% CI 0.14-0.75). The results are compatible with an effect of reproductive history-related factors on melanoma risk, but also could reflect differences in other factors, such as sun exposure history.

Adult↗

PubMed2006

Race and surgical mortality in the United States.

OBJECTIVE: This study describes racial differences in postoperative mortality following 8 cardiovascular and cancer procedures and assesses possible explanations for these differences. SUMMARY BACKGROUND DATA: Although racial disparities in the use of surgical procedures are well established, relationships between race and operative mortality have not been assessed systematically. METHODS: We used national Medicare data to identify all patients undergoing one of 8 cardiovascular and cancer procedures between 1994 and 1999. We used multiple logistic regression to assess differences in operative mortality (death within 30 days or before discharge) between black patients and white patients, controlling for patient characteristics. Adding hospital indicators to these models, we then assessed the extent to which racial differences in operative mortality could be accounted for by the hospital in which patients were cared for. RESULTS: Black patients had higher crude mortality rates than white patients for 7 of the 8 operations, including coronary artery bypass, aortic valve replacement, abdominal aortic aneurysm repair, carotid endarterectomy, radical cystectomy, pancreatic resection, and esophagectomy. Among these 7 procedures, odds ratios of mortality (black versus white) ranged from 1.23 (95% confidence interval, 1.18-1.29) for CABG to 1.61 (95% confidence interval, 1.28-2.03) for esophagectomy. Adjusting for patient characteristics had modest or no effect on odds ratios of mortality by race. However, there remained few clinically or statistically significant differences in mortality by race after we accounted for hospital. Hospitals that treated a large proportion of black patients had higher mortality rates for all 8 procedures, for white as well as black patients. CONCLUSIONS: Black patients have higher operative mortality risks across a wide range of surgical procedures, in large part because of higher mortality rates at the hospitals they attend.

Aged↗

PubMed2006

Volume matters: physician practice characteristics and immunization coverage among young children insured through a universal health plan.

OBJECTIVES: We studied the association between immunization coverage for a cohort of 2-year-old children covered by a universal health insurance plan and pediatric provider and other health services characteristics. METHODS: We assembled a cohort of 101,570 infants born in urban areas in Ontario, Canada, between July 1, 1997, and June 31, 1998. Children were considered to have up-to-date (UTD) immunization coverage if they had > or =5 immunizations by 2 years of age, ie, the recommended 3 doses and 1 booster of diphtheria-polio-tetanus-pertussis/Haemophilus influenzae type b vaccine and 1 dose of measles-mumps-rubella vaccine. Provider practice characteristics were derived from outpatient billing records, and 1996 census data were used to derive neighborhood income quintiles. The association between UTD immunization status and provider characteristics was assessed with multilevel regression models, controlling for patient characteristics. RESULTS: Overall, the rate of complete UTD immunization coverage was low (66.3%) despite a large number of primary care visits (median: 19 visits). Children whose usual provider had a low volume of pediatric primary care were less than one half as likely to be UTD. Other factors associated with not being UTD included very low continuity of care, low continuity of care, and usual provider in practice for <5 years. With adjustment for patient and provider characteristics, there was no difference in immunization coverage for general practitioners versus pediatricians. Children from low-income neighborhoods were less likely to be UTD. CONCLUSIONS: Despite universal access to primary care services, rates of complete immunization coverage among 2-year-old children in Ontario are low. Because visit rates are high, primary care reform should include interventions directed at provider immunization practices to reduce missed opportunities.

Child, Preschool↗

PubMed2005

Risk-treatment mismatch in the pharmacotherapy of heart failure.

CONTEXT: Patients with heart failure have a wide spectrum of mortality risks. To maximize the benefit of available pharmacotherapies, patients with high mortality risk should receive high rates of drug therapy. OBJECTIVE: To examine patterns of drug therapy and underlying mortality risk in patients with heart failure. DESIGN, SETTING, AND PATIENTS: In the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) population-based cohort (1999-2001) of 9942 patients with heart failure hospitalized in Ontario, Canada, we evaluated 1418 patients with documented left ventricular ejection fraction of 40% or less and aged 79 years or younger with low-, average-, and high-predicted risk of death within 1 year; all patients survived to hospital discharge. Administration of angiotensin-converting enzyme (ACE) inhibitors, ACE inhibitors or angiotensin II receptor blockers (ARBs), and beta-adrenoreceptor antagonists was evaluated according to predicted risk of death. MAIN OUTCOME MEASURE: Heart failure drug administration rates at time of discharge and 90 days after hospital discharge. RESULTS: At hospital discharge, prescription rates for patients in the low-, average-, and high-risk groups were 81%, 73%, 60%, respectively, for ACE inhibitors; 86%, 80%, 65%, respectively, for ACE inhibitors or ARBs; and 40%, 33%, 24%, respectively, for beta-adrenoreceptor antagonists (all P<.001 for trend). Within 90 days following hospital discharge, the rates were 83%, 76%, and 61% for ACE inhibitors; 89%, 83%, and 67% for ACE inhibitors or ARBs; and 43%, 36%, and 28% for beta-adrenoreceptor antagonists for the 3 risk groups, respectively (all P<.001 for trend). The pattern of lower rates of drug administration in those patients at increasing risk was maintained up to 1 year postdischarge (P<.001). After accounting for varying survival time and potential contraindications to therapy, low-risk patients were more likely to receive ACE inhibitors or ARBs (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.49-1.74) and beta-adrenoreceptor antagonists (HR, 1.80; 95% CI, 1.60-2.01) compared with high-risk patients (both P<.001). CONCLUSIONS: Patients with heart failure at greatest risk of death are least likely to receive ACE inhibitors, ACE inhibitors or ARBs, and beta-adrenoreceptor antagonists. Understanding the reasons underlying this mismatch may facilitate improvements in care and outcomes for patients with heart failure.

Adrenergic beta-Antagonists↗

PubMed2005

Atypical antipsychotics and parkinsonism.

BACKGROUND: Atypical antipsychotic agents are thought to be less likely than older typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed atypical relative to typical antipsychotics. METHODS: Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up. RESULTS: All 25,769 older adults prescribed antipsychotics were observed for 11,573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an atypical antipsychotic, those dispensed a typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency typical antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to atypical antipsychotics. Relative to those dispensed a high-dose atypical antipsychotic, those dispensed a typical antipsychotic were at similar risk for parkinsonism (Wald chi(2) = 0.14, P = .7). CONCLUSIONS: The risk of development of parkinsonism associated with the use of high-dose atypical antipsychotics was similar to that associated with the use of typical antipsychotics. Caution should be used when prescribing atypical antipsychotic therapy at high doses.

Aged↗

PubMed2005

The use of the propensity score for estimating treatment effects: administrative versus clinical data.

There is an increasing interest in using administrative data to estimate the treatment effects of interventions. While administrative data are relatively inexpensive to obtain and provide population coverage, they are frequently characterized by lack of clinical detail, often leading to problematic confounding when they are used to conduct observational research. Propensity score methods are increasingly being used to address confounding in estimating the effects of interventions in such studies. Using data on patients discharged from hospital for whom both administrative data and detailed clinical data obtained from chart reviews were available, we examined the degree to which stratifying on the quintiles of propensity scores derived from administrative data was able to balance patient characteristics measured in clinical data. We also determined the extent to which measures of treatment effect obtained using propensity score methods were similar to those obtained using traditional regression methods. As a test case, we examined the treatment effects of ASA and beta-blockers following acute myocardial infarction. We demonstrated that propensity scores developed using administrative data do not necessarily balance patient characteristics contained in clinical data. Furthermore, measures of treatment effectiveness were attenuated when obtained using clinical data compared to when administrative data were used.

Adrenergic beta-Antagonists↗

PubMed2005

Influence analysis for linear mixed-effects models.

In this paper, we extend several regression diagnostic techniques commonly used in linear regression, such as leverage, infinitesimal influence, case deletion diagnostics, Cook's distance, and local influence to the linear mixed-effects model. In each case, the proposed new measure has a direct interpretation in terms of the effects on a parameter of interest, and collapses to the familiar linear regression measure when there are no random effects. The new measures are explicitly defined functions and do not necessitate re-estimation of the model, especially for cluster deletion diagnostics. The basis for both the cluster deletion diagnostics and Cook's distance is a generalization of Miller's simple update formula for case deletion for linear models. Pregibon's infinitesimal case deletion diagnostics is adapted to the linear mixed-effects model. A simple compact matrix formula is derived to assess the local influence of the fixed-effects regression coefficients. Finally, a link between the local influence approach and Cook's distance is established. These influence measures are applied to an analysis of 5-year Medicare reimbursements to colon cancer patients to identify the most influential observations and their effects on the fixed-effects coefficients.

Cluster Analysis↗