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Title: Warfarin Therapy for an Octogenarian Who has Atrial Fibrillation.
Publication: Annals of Internal Medicine 2001;134(6):465-74.
Authors: Gage BF et al.
Grant No.: HS10133.
Principal Investigator: Brian Gage.
Project Officer: Daniel Stryer.
Abstract: In North America, atrial fibrillation is associated with at least 75,000 ischemic strokes each year. Most of these strokes occur in patients older than 75 years of age. The high incidence of stroke in very elderly persons reflects the increasing prevalence of atrial fibrillation that occurs with advanced age, the high incidence of stroke in elderly patients, and the failure of physicians to prescribe antithrombotic therapy in most of these patients. This failure is related to the increased risk for major hemorrhage with advanced age, obfuscating the decision to institute stroke prophylaxis with antithrombotic therapy. This case-based review describes the risk and benefits of prescribing antithrombotic therapy for a hypothetical 80-year-old man who has atrial fibrillation and hypertension, and it offers practical advice on managing warfarin therapy. After concluding that the benefits of warfarin outweigh its risks in this patient, we describe how to initiate warfarin therapy cautiously and how to monitor and dose the drug. We then review five recent randomized, controlled trials that document the increased risk for stroke when an international normalized ratio (INR) of less than 2.0 is targeted among patients with atrial fibrillation. Next, we make the case that cardioversion is not needed for this asymptomatic patient with chronic atrial fibrillation. Instead, we choose to leave the patient in atrial fibrillation and to control his ventricular rate with atenolol. Later, when the INR increases to 4.9, we advocate withholding one dose of warfarin and repeating the INR test. Finally, when the patient develops dental pain, we review the analgesic agents that are safe to take with warfarin and explain why warfarin therapy does not have to be interrupted during a subsequent dental extraction.
Title: Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.
Publication: Journal of American Medical Association 2001 Jun 13;285(22):2864-70.
Authors: Gage BF et al.
Grant No.: HS10133.
Principal Investigator: Brian Gage.
Project Officer: Daniel Stryer.
Abstract: CONTEXT: Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. OBJECTIVE: To assess the predictive value of classification schemes that estimate stroke risk in patients with AF. DESIGN, SETTING, AND PATIENTS: Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all three classification schemes were validated. The CHADS(2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1,733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge. MAIN OUTCOME MEASURE: Hospitalization for ischemic stroke, determined by Medicare claims data. RESULTS: During 2,121 patient-years of followup, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the two existing classification schemes predicted stroke better than chance: c of 0.68 (95 percent confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95 percent CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95 percent CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95 percent CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95 percent CI, 1.2-3.0) for a score of 0; 2.8 (95 percent CI, 2.0-3.8) for 1; 4.0 (95 percent CI, 3.1-5.1) for 2; 5.9 (95 percent CI, 4.6-7.3) for 3; 8.5 (95 percent CI, 6.3-11.1) for 4; 12.5 (95 percent CI, 8.2-17.5) for 5; and 18.2 (95 percent CI, 10.5-27.4) for 6. CONCLUSION: The two existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.
Title: Preoperative correlates of the cost of coronary artery bypass graft surgery: comparison of results from three hospitals.
Publication: American Journal of Medical Quality 2001 May-Jun;16(3):87-92.
Authors: Subramanian S et al.
Grant No.: HS09559.
Principal Investigator: Chuan-Fen Liu.
Project Officer: Daniel Stryer.
Abstract: This article furthers our understanding of the cost of coronary artery bypass graft (CABG) surgery by analyzing the extent to which preoperative correlates of cost differ among hospitals. A total of 2,828 patients who underwent bypass surgery at three hospitals (two teaching and one nonteaching) were analyzed. The preoperative correlates of direct variable cost (marginal cost) were determined by ordinary least squares regression. Age, urgent/emergent surgical priority, previous CABG, and chronic obstructive pulmonary disease (COPD) were significant contributors (P < .05) to cost in all hospitals, but overall, there were many differences. The major contributor to cost was non-white race (31.3 percent) at teaching hospital A, previous CABG (30.5 percent) at teaching hospital B, and preop insertion of intra-aortic balloon pump (IABP) (35.9 percent) at the nonteaching hospital. The number of significant risk factors also differed. Preoperative characteristics that contribute to cost can be quite different among hospitals and therefore results from one hospital cannot be broadly generalized to others.
Title: Impact of global bundled payments on hospital costs of coronary artery bypass grafting.
Publication: Journal Health Care Finance 2001 Summer;27(4):39-54.
Authors: Liu CF et al.
Grant No.: HS09559.
Principal Investigator: Chuan-Fen Liu.
Project Officer: Daniel Stryer.
Abstract: The Health Care Financing Administration began the Medicare Participating Heart Bypass Center Demonstration in 1991, in which hospitals and physicians are paid a single negotiated global price for all inpatient care for heart bypass patients. This article analyzed the changes in total and departmental direct variable costs during the 1991-93 period using micro-cost data. The results indicate that all participating hospitals had significant reductions in total direct variable costs, after controlling for preoperative risk factors and postoperative outcomes. However, the patterns in cost reductions across major departments were different across hospitals. The cost reductions primarily came from nursing intensive care unit, routine nursing, pharmacy, and catheter lab.
Title: Cost reduction and implantable cardioverter defibrillator implantation.
Publication: Journal of Cardiovascular Electrophysiology 2001 Feb;12(2):167-8.
Authors: McDonald KM et al.
Grant No.: HS08362.
Principal Investigator: Mark Hlatky.
Project Officer: Daniel Stryer.
Title: Using observational data to estimate prognosis: an example using a coronary artery disease registry.
Publication: Stat Med 2001 Aug 30;20(16):2505-32.
Authors: DeLong ER et al.
Grant No.: HS06503 HS08805.
Principal Investigator: Elizabeth Delong.
Project Officer: Heddy Hubbard Steven Fox.
Abstract: With the proliferation of clinical data registries and the rising expense of clinical trials, observational data sources are increasingly providing evidence for clinical decision making. These data are viewed as complementary to randomized clinical trials (RCT). While not as rigorous a methodological design, observational studies yield important information about effectiveness of treatment, as compared with the efficacy results of RCTs. In addition, these studies often have the advantage of providing longer-term followup, beyond that of clinical trials. Hence, they are useful for assessing and comparing patients' long-term prognosis under different treatment strategies. For patients with coronary artery disease, many observational comparisons have focused on medical therapy versus interventional procedures. In addition to the well-studied problem of treatment selection bias (which is not the focus of the present study), three significant methodological problems must be addressed in the analysis of these data: (i) designation of the therapeutic arms in the presence of early deaths, withdrawals, and treatment cross-overs; (ii) identification of an equitable starting point for attributing
survival time; (iii) site to site variability in short-term mortality. This paper discusses these issues and suggests strategies to deal with them. A proposed methodology is developed, applied and evaluated on a large observational database that has long-term followup on nearly 10,000 patients.
Title: Impact of underuse, overuse, and discretionary use on geographic variation in the use of coronary angiography after acute myocardial infarction.
Publication: Medical Care 2001 May;39(5):446-58.
Authors: Guadagnoli E et al.
Grant No.: HS08071.
Principal Investigator: Barbara McNeil.
Project Officer: Mary Cummings.
Abstract: BACKGROUND: Geographic variation in the use of medical procedures has been well documented. However, it is not known whether this variation is due to differences in use when procedures are indicated, discretionary, or contraindicated. OBJECTIVES: To examine whether use of coronary angiography after acute myocardial infarction (AMI) according to appropriateness criteria varied across geographic regions and whether underuse, overuse, or discretionary use accounted for variation in overall use. DESIGN: Retrospective cohort study using data from the Cooperative Cardiovascular Project. SETTING: Ninety-five hospital referral regions. PATIENTS: There were 44,294 Medicare patients hospitalized with AMI during 1994 or 1995, classified according to appropriateness for angiography. MAIN OUTCOME MEASURE: Variation in use of angiography, as measured by the difference between high and low rates of use across regions. RESULTS: Across regions, variation in the use of angiography was similar for indications judged necessary; appropriate, but not necessary; or uncertain. Variation was lowest for indications judged unsuitable (difference between high rate and low rate across regions = 16.3 percent; 95 percent CI = 12.6 percent; 20.6 percent). The primary cause of variation in the overall rate of angiography was due to use for indications judged appropriate, but not necessary or uncertain. When variation associated with these indications was accounted for, the difference between the resulting high and low overall rates was 10.8 percent (9.4 percent, 12.4 percent). In contrast, variation in the overall rate remained high when underuse in necessary situations or overuse in unsuitable situations was accounted for. CONCLUSIONS: Across regions, practice was more similar for patients categorized unsuitable for angiography than for patients with other indications. Variation in overall use of angiography appeared to be driven by utilization for discretionary indications rather than by underuse or overuse. If equivalent rates across geographic areas are judged desirable, then greater effort must be directed toward defining care for patients with discretionary indications.
Title: Validating recommendations for coronary angiography following acute myocardial infarction in the elderly; a matched analysis using propensity scores.
Publication: Journal of Clinical Epidemiology 2001 Apr;54(4):387-98.
Authors: Normand ST el al.
Grant No.: HS08071.
Principal Investigator: Barbara McNeil.
Project Officer: Mary Cummings.
Abstract: We determined whether adherence to recommendations for coronary angiography more than 12 hours after symptom onset but prior to hospital discharge after acute myocardial infarction (AMI) resulted in better survival. Using propensity scores, we created a matched retrospective sample of 19,568 Medicare patients hospitalized with AMI during 1994-1995 in the United States. Twenty-nine percent, 36 percent, and 34 percent of patients were judged necessary, appropriate, or uncertain, respectively, for angiography while 60 percent of those judged necessary received the procedure during the hospitalization. The 3-year survival benefit was largest for patients rated necessary [mean survival difference (95 percent CI): 17.6 percent (15.1, 20.1)] and smallest for those rated uncertain [8.8 percent (6.8, 10.7)]. Angiography recommendations appear to select patients who are likely to benefit from the procedure and the consequent interventions. Because of the magnitude of the benefit and of the number of patients involved, steps should be taken to replicate these findings.
Title: Quality of care for coronary heart disease in two countries.
Publication: Health Affairs 2001 May/Jun; 20(3):55-67.
Authors: Ayanian JZ et al.
Grant No.: HS08071.
Principal Investigator: Barbara McNeil.
Project Officer: Mary Cummings.
Abstract: Coronary heart disease is the leading cause of death in the United States and England, and each country devotes substantial resources to its prevention and treatment. We review recent strategies for improving quality of care for coronary heart disease in each country, including clinical guidelines; national standards; performance reports; benchmarking, feedback, and professional leadership; and market-oriented approaches. These strategies highlight the importance of information systems, organizational culture, and incentives to improve the quality of care in both the decentralized health care system of the United States and England's more centralized system.
Title: Quality of Ambulatory Care after Myocardial Infarction among Medicare Patients by Type of Insurance and Region.
Publication: American Journal of Medicine 2001 Jul;111(1):24-32.
Authors: Seddon ME et al.
Grant No.: HS06503/HS08071.
Principal Investigator: Barbara McNeil.
Project Officer: Mary Cummings.
Abstract: PURPOSE: To evaluate use of effective cardiac medications and rehabilitation after myocardial infarction in the ambulatory setting in health maintenance organizations (HMOs) and fee-for-service care, and by region. SUBJECTS AND METHODS: We surveyed elderly Medicare patients during 1996 and 1997 in California (n = 516), Florida (n = 304), and the Northeast (n = 220; Massachusetts, New York, and Pennsylvania) approximately 18 months after myocardial infarction. We assessed use of cardiac medications and rehabilitation for HMO (n = 520) and fee-for-service (n = 520) patients matched by age, sex, month of infarct, and region. RESULTS: Across all regions, similar proportions of HMO and fee-for-service patients were using aspirin (72 percent, n = 374 vs. 74 percent, n = 387), beta-blockers (38 percent, n = 195 vs. 32 percent, n =168), angiotensin-converting enzyme inhibitors (31 percent, n = 159 vs. 29 percent, n = 148), cholesterol-lowering agents (28 percent, n = 146 vs. 30 percent, n = 157), and calcium channel blockers (31 percent, n = 162 vs. 31 percent, n = 159; all P >0.07), except in California where more HMO patients received beta-blockers (36 percent, n = 93 vs. 26 percent, n = 66, P = 0.01). In adjusted analyses, use of these drugs did not differ significantly between HMO and fee-for-service patients. Substantial regional differences were evident in the use of beta-blockers (Northeast 46 percent, n = 102; Florida 34 percent, n = 102; California 31 percent, n = 159) and cholesterol-lowering agents (California 35 percent, n =182; Florida 24 percent, n = 73; Northeast 22 percent, n = 48; each P <0.001). Fee-for-service patients were more likely than HMO patients to receive cardiac rehabilitation in unadjusted (32 percent, n =167, vs. 22 percent, n = 141, P = 0.001) and adjusted analyses. CONCLUSIONS: Both HMO and fee-for-service patients would likely benefit from greater use of beta-blockers and cholesterol-lowering agents. Professional fees for cardiac rehabilitation may promote increased use among fee-for-service patients. Future studies should assess the quality of ambulatory cardiac care in different types of HMOs and the reasons for geographic variations in cardiac drug use.
Title: Usefulness of transthoracic echocardiography as a tool for risk stratification of patients undergoing major non-cardiac surgery.
Publication: American Journal of Cardiology 2001 Mar 1;87(5):505-9.
Authors: Rohde LE et al.
Grant No.: HS06573.
Principal Investigator: Lee Goldman.
Project Officer: Joanne Book.
Abstract: Transthoracic echocardiography (TTE) is frequently ordered before noncardiac surgery, although its ability to predict perioperative cardiac complications is uncertain. To evaluate the incremental information provided by TTE after consideration of clinical data for prediction of cardiac complications after noncardiac surgery, 570 patients who underwent TTE before major noncardiac surgery at a university hospital were studied. Preoperative clinical data and clinical outcomes were collected prospectively according to a structured protocol. TTE data included left ventricular (LV) function, hypertrophy indexes, and Doppler-derived measurements. In univariate analyses, preoperative systolic dysfunction was associated with postoperative myocardial infarction (odds ratio [OR] 2.8, 95 percent confidence interval [CI] 1.1 to 7.0), cardiogenic pulmonary edema (OR 3.2, 95 percent CI 1.4 to 7.0), and major cardiac complications (OR 2.4, 95 percent Cl 1.3 to 4.5). Moderate to severe LV hypertrophy, moderate to severe mitral regurgitation, and increased aortic valve gradient were also associated with major cardiac events (OR 2.3, 95 percent CI 1.2 to 4.6; OR 2.2, 95 percent CI 1.1 to 4.3; OR 2.1, 95 percent CI 1.0 to 4.5, respectively). In logistic regression analysis, models with echocardiographic variables predicted major cardiac complications significantly better than those that included only clinical variables c statistic 0.73 vs 0.68; p <0.05). Echocardiographic data added significant information for patients at increased risk for cardiac complications by clinical criteria, but not in otherwise low-risk patients. In conclusion, preoperative TTE before noncardiac surgery can provide independent information about the risk of postoperative cardiac complications in selected patients.
Title: Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery.
Publication: Annals of Internal Medicine 2001 Apr;134(8):637-43.
Authors: Polanczyk CA et al.
Grant No.: HS06573.
Principal Investigator: Lee Goldman.
Project Officer: Joanne Book.
Abstract: BACKGROUND: Major surgical procedures are performed with increasing frequency in elderly persons, but the impact of age on resource use and outcomes is uncertain. OBJECTIVE: To evaluate the influence of age on perioperative cardiac and noncardiac complications and length of stay in patients undergoing noncardiac surgery. DESIGN: Prospective cohort study. SETTING: Urban academic medical center. PATIENTS: Consecutive sample of 4,315 patients 50 years of age or older who underwent nonemergent major noncardiac procedures. MEASUREMENTS: Major perioperative complications (cardiac and noncardiac), in-hospital mortality, and length of stay. RESULTS: Major perioperative complications occurred in 4.3 percent (44 of 1,015) of patients 59 years of age or younger, 5.7 percent (93 of 1,646) of patients 60 to 69 years of age, 9.6 percent (129 of 1,341) of patients 70 to 79 years of age, and 12.5 percent (39 of 313) of patients 80 years of age or older (P < 0.001). In-hospital mortality was significantly higher in patients 80 years of age or older than in those younger than 80 years of age (0.7 percent vs. 2.6 percent, respectively). Multivariate analyses indicated an increased odds ratio for perioperative complications or in-hospital mortality in patients 70 to 79 years of age (1.8 [95 percent CI, 1.2 to 2.7]) and those 80 years of age or older (OR, 2.1 [CI, 1.2 to 3.6]) compared with patients 50 to 59 years of age. Patients 80 years of age or older stayed an average of 1 day more in the hospital, after adjustment for other clinical data (P = 0.001). CONCLUSIONS: Elderly patients had a higher rate of major perioperative complications and mortality after noncardiac surgery and a longer length of stay, but even in patients 80 years of age or older, mortality was low.
Title: Right heart catheterization and cardiac complications in patients undergoing noncardiac surgery: an observational study.
Publication: Journal of American Medical Association 2001 Jul 18;286(3):309-14.
Authors: Polanczyk CA et al.
Grant No.: HS06573.
Principal Investigator: Lee Goldman.
Project Officer: Joanne Book.
Abstract: CONTEXT: Right heart catheterization (RHC) is commonly performed before high-risk noncardiac surgery, but the benefit of this strategy remains unproven. OBJECTIVE: To evaluate the relationship between use of perioperative RHC and postoperative cardiac complication rates in patients undergoing major noncardiac surgery. DESIGN: Prospective, observational cohort study. SETTING: Tertiary care teaching hospital in the United States. PATIENTS: Patients (n = 4,059 aged >/=50 years)who underwent major elective noncardiac procedures with an expected length of stay of 2 or more days between July 18, 1989, and February 28, 1994. Two hundred twenty-one patients had RHC and 3,838 did not. MAIN OUTCOME MEASURE: Combined end point of major postoperative cardiac events, including myocardial infarction, unstable angina, cardiogenic pulmonary edema, ventricular fibrillation, documented ventricular tachycardia or primary cardiac arrest, and sustained complete heart block, classified by a reviewer blinded to preoperative data. RESULTS: Major cardiac events occurred in 171 patients (4.2 percent). Patients who underwent perioperative RHC had a 3-fold increase in incidence of major postoperative cardiac events (34 [15.4 percent] vs 137 [3.6 percent]; P<.001). In multivariate analyses, the adjusted odds ratios (ORs) for postoperative major cardiac and noncardiac events in patients undergoing RHC were 2.0 (95 percent confidence interval [CI], 1.3-3.2) and 2.1 (95 percent CI, 1.2-3.5), respectively. In a case-control analysis of a subset of 215 matched pairs of patients who did and did not undergo RHC, adjusted for propensity of RHC and type of procedure, patients who underwent perioperative RHC also had increased risk of postoperative congestive heart failure (OR, 2.9; 95 percent CI, 1.4-6.2) and major noncardiac events (OR, 2.2; 95 percent CI, 1.4-4.9). CONCLUSIONS: No evidence was found of reduction in complication rates associated with use of perioperative RHC in this population. Because of the morbidity and the high costs associated with RHC, the impact of this intervention in perioperative care should be evaluated in randomized trials.
Title: Adverse intraoperative medical events and their association with anesthesia management strategies in cataract surgery.
Publication: Ophthalmology 2001 Oct;108(10): 1721-6.
Authors: Katz J et al.
Grant No.: HS08331.
Principal Investigator: Oliver Schein.
Project Officer: Heddy Hubbard.
Abstract: OBJECTIVE: To compare adverse medical events by different anesthesia strategies for cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Patients 50 years of age and older undergoing 19,250 cataract surgeries at nine centers in the United States and Canada between June 1995 and June 1997. INTERVENTION: Local anesthesia applied topically or by injection, with or without oral and intravenous sedatives, opioid analgesia, hypnotics, and diphenhydramine (Benadryl). MAIN OUTCOME MEASURES: Intraoperative and postoperative adverse medical events. RESULTS: Twenty-six percent of surgeries were performed with topical anesthesia and the remainder with injection anesthesia. There was no increase in deaths and hospitalizations associated with any specific anesthesia strategy. No statistically significant difference was observed in the prevalence of intraoperative events between topical and injection anesthesia without intravenous sedatives (0.13 percent and 0.78 percent, respectively). The use of intravenous sedatives was associated with a significant increase in adverse events for topical (1.20 percent) and injection anesthesia (1.18 percent), relative to topical anesthesia without intravenous sedation. The use of short-acting hypnotic agents with injection anesthesia was also associated with a significant increase in adverse events when used alone (1.40 percent) or in combination with opiates (1.75 percent), sedatives (2.65 percent), and with the combination of opiates and sedatives (4.04 percent). These differences remained after adjusting for age, gender, duration of surgery, and American Society of Anesthesiologists risk class. CONCLUSIONS: Adjuvant intravenous anesthetic agents used to decrease pain and alleviate anxiety are associated with increases in medical events. However, cataract surgery is a safe procedure with a low absolute risk of medical complications with either topical or injection anesthesia. Clinicians should weigh the risks and benefits of their use for individual patients.
Title: Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study.
Publication: Lancet 2002 Jan;359:118-23.
Authors: Ray WA et al.
Grant No.: HS10384.
Principal Investigator: Wayne Ray.
Project Officer: Lynn Bosco.
Abstract: FINDINGS: during 532 634 person-years of followup, 6362 cases of serious coronary heart disease occurred, or 11·9 per 1000 person/years. Multivariate-adjusted rate ratios for current and former use of NANSAIDs were 1·05 (95percent CI 0·97-1·14) and 1·02 (0·97-1·08), respectively. Rate ratios for naproxen, ibuprofen, and other NANSAIDs were 0·95 (0·82-1·09), 1·15 (1·02-1·28), and 1·03 (0·92-1·16), respectively. There was no protection among long-term NANSAID users with uninterrupted use; the rate ratio among current users with more than 60 days of continuous use was 1·05 (0·91-1·21). When naproxen was directly compared with ibuprofen, the current-use rate ratio was 0·83 (0·69-0·98). INTERPRETATION: Absence of a protective effect of naproxen or other NANSAIDs on risk of coronary heart disease suggests that these drugs should not be used for cardioprotection.
Title: Resolved: Low-dose glucocorticoids are neither safe nor effective for the long-term treatment of rheumatoid arthritis.
Publication: Arthritis Rheum 2001 Oct;45(5):468-71.
Authors: Saag KG.
Grant No.: HS10389.
Principal Investigator: Kenneth Saag.
Project Officer: Lynn Bosco.
Title: Possible Medication Errors in Home Healthcare Patients.
Publication: Journal of American Geriatrics Society 200149:719-24.
Authors: Meredith S, Feldman PH, Frey D, Hall K, Arnold K, Brown NJ, Ray WA.
Grant No.: HS10384.
Principal Investigator: Wayne Ray.
Project Officer: Lynn Bosco.
Abstract: OBJECTIVE: To determine the frequency of possible medication errors in a population of older home healthcare patients according to expert panel objective criteria. DESIGN: A cross-sectional survey. SETTING: Two of the largest urban home health care agencies in the United States. PARTICIPANTS: Home healthcare patients age 65 and older admitted to selected offices of these agencies between October 1996 and September 1998. MEASUREMENTS: We used two sets of consensus-based expert panel criteria to define possible medication errors. The Home Health Criteria identify patients with patterns of medication use and signs and symptoms that indicate sufficient likelihood of a medication-related problem to warrant reevaluating the patient. The Beers criteria identify medications that experts have deemed generally inappropriate for older patients. RESULTS: The 6,718 study subjects took a median of five drugs; 19 percent were taking nine or more medications. A possible medication error was identified for 19 percent of patients according to Home Health Criteria, 17 percent according to the Beers criteria, and 30 percent according to either. Possible errors increased linearly with number of medications taken. When patients taking one to three medications were compared with those taking nine or more drugs, the percentages with possible errors were, respectively, 10 percent and 32 percent for the Home Health Criteria, 8 percent and 32 percent for the Beers criteria, and 16 percent and 50 percent for both. CONCLUSION: Nearly one-third of the home healthcare patients surveyed had evidence of a potential medication problem or were taking a drug considered inappropriate for older people. More effective methods are needed to improve medication use in this vulnerable population.
Title: Adjustments for Center in Multicenter Studies: An Overview.
Publication: Annals of Internal Medicine 2001 Jul 17;135(2):112-23.
Authors: Localio AR et al.
Grant No.: HS10399.
Principal Investigator: Brian Strom.
Project Officer: Lynn Bosco.
Abstract: Increasingly, investigators rely on multicenter or multigroup studies to demonstrate effectiveness and generalizability. Authors too often overlook the analytic challenges in these study designs: the correlation of outcomes and exposures among patients within centers, confounding of associations by center, and effect modification of treatment or exposure across center. Correlation or clustering, resulting from the similarity of outcomes among patients within a center, requires an adjustment to confidence intervals and P values, especially in observational studies and in randomized multicenter studies in which treatment is allocated by center rather than by individual patient. Multicenter designs also warrant testing and adjustment for the potential bias of confounding by center, and for the presence of effect modification or interaction by center. This paper uses examples from the recent biomedical literature to highlight the issues and analytic options.
Title: Drug-induced QT Prolongation in Women During the Menstrual Cycle.
Publication: Journal of American Medical Association 2001;285(10):1322-26.
Authors: Rodriguez I et al.
Grant No.: HS10385.
Principal Investigator: Raymond Woosley.
Project Officer: Lynn Bosco.
Abstract: CONTEXT: Women have a higher incidence of torsades de pointes than men, but it is not known if the risk of drug-induced torsades de pointes varies during the menstrual cycle. OBJECTIVES: To determine if the degree of QT prolongation in response to ibutilide varies with the menstrual cycle phase and to compare QT prolongation between women and men. DESIGN AND SETTING: Cohort study of men and women who received the same intervention conducted between November 1998 and November 2000 at a general clinical research center of a university hospital. PARTICIPANTS: A volunteer sample of 58 healthy adults (38 men and 20 women) aged 21 to 40 years. INTERVENTION: A low dose of ibutilide (0.003 mg/kg), infused intravenously for 10 minutes. Subjects were monitored for 120 minutes. Women received the intervention on 3 separate occasions to correspond with menstrual cycle phases, which were verified by using hormonal assays. MAIN OUTCOME MEASURE: QT interval, recorded from electrocardiogram at timed intervals during and after ibutilide infusion and standardized for variations in heart rate (QTc). RESULTS: Maximum (mean [SD]) millisecond increase in QTc after ibutilide infusion was greater for women during menses (63 [13]) and the ovulatory phase (59 [17]) compared with women during the luteal phase (53 [14]) and compared with men (46 [16]; P =.002 vs menses and P =.007 vs ovulation). Progesterone (r = -0.40) and progesterone-to-estradiol ratio (r = -0.41), but not estradiol (r = 0.14) or testosterone (r = 0.09), were inversely correlated with ibutilide-induced QT prolongation. CONCLUSIONS: Menstrual cycle and sex differences exist in QTc responses to ibutilide, with the greatest increase in QTc corresponding to the first half of the menstrual cycle.