Prevalence of Intracranial Atherosclerotic Disease in Patients with Low-Risk Transient or Persistent Neurologic Events.

BACKGROUND AND PURPOSE: There are limited data on the prevalence and outcome of intracranial atherosclerotic disease in patients with low-risk transient or persistent minor neurologic events. We sought to determine the prevalence and risk factors associated with intracranial atherosclerotic disease in patients with low-risk transient or persistent neurologic events. MATERIALS AND METHODS: Participants with available intracranial vascular imaging from the Diagnosis of Uncertain-Origin Benign Transient Neurologic Symptoms (DOUBT) study, a large prospective multicenter cohort study, were included in this post hoc analysis. The prevalence of intracranial atherosclerotic disease of ≥50% was determined, and the association with baseline characteristics and DWI lesions was evaluated using logistic regression. RESULTS: We included 661 patients with a median age of 62 years (interquartile range, 53-70 years), of whom 53% were women. Intracranial atherosclerotic disease was found in 81 (12.3%) patients; asymptomatic intracranial atherosclerotic disease alone, in 65 (9.8%); and symptomatic intracranial atherosclerotic disease, in 16 (2.4%). The most frequent location was in the posterior cerebral artery (29%). Age was the only factor associated with any intracranial atherosclerotic disease (adjusted OR, 1.9 for 10 years increase; 95% CI, 1.6-2.5). Multivariable logistic regression showed a strong association between intracranial atherosclerotic disease and the presence of acute infarct on MR imaging (adjusted OR, 3.47; 95% CI, 1.91-6.25). CONCLUSIONS: Intracranial atherosclerotic disease is not rare in patients with transient or persistent minor neurologic events and is independently associated with the presence of MR imaging-proved ischemia in this context. Evaluation of the intracranial arteries could be valuable in establishing the etiology of such low-risk events.

Utstein recommendation for emergency stroke care.

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. CONCLUSIONS: Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability.

Prediction of Hemorrhage after Successful Recanalization in Patients with Acute Ischemic Stroke: Improved Risk Stratification Using Dual-Energy CT Parenchymal Iodine Concentration Ratio Relative to the Superior Sagittal Sinus.

BACKGROUND AND PURPOSE: Brain parenchymal hyperdensity on postthrombectomy CT in patients with acute stroke can be due to hemorrhage and/or contrast staining. We aimed to determine whether iodine concentration within contrast-stained parenchyma compared with an internal reference in the superior sagittal sinus on dual-energy CT could predict subsequent intracerebral hemorrhage. MATERIALS AND METHODS: Seventy-one patients with small infarct cores (ASPECTS ≥ 7) and good endovascular recanalization (modified TICI 2b or 3) for anterior circulation large-vessel occlusion were included. Brain parenchymal iodine concentration as per dual-energy CT and the percentage of contrast staining relative to the superior sagittal sinus were recorded and correlated with the development of intracerebral hemorrhage using Mann-Whitney U and Fisher exact tests. RESULTS: Forty-three of 71 patients had parenchymal hyperdensity on initial dual-energy CT. The median relative iodine concentration compared with the superior sagittal sinus was significantly higher in those with subsequent intracerebral hemorrhage (137.9% versus 109.2%, P = .007). By means of receiver operating characteristic analysis, a cutoff value of 100% (iodine concentration relative to the superior sagittal sinus) enabled identification of patients going on to develop intracerebral hemorrhage with 94.75% sensitivity, 43.4% specificity, and a likelihood ratio of 1.71. CONCLUSIONS: Within our cohort of patients, the relative percentage of iodine concentration at dual-energy CT compared with the superior sagittal sinus was a reliable predictor of intracerebral hemorrhage development and may be a useful imaging biomarker for risk stratification after endovascular treatment.

Clot Burden Score and Early Ischemia Predict Intracranial Hemorrhage following Endovascular Therapy.

BACKGROUND AND PURPOSE: Intracranial hemorrhage is a known complication following endovascular thrombectomy. The radiologic characteristics of a CT scan may assist with hemorrhage risk stratification. We assessed the radiologic predictors of intracranial hemorrhage following endovascular therapy using data from the INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) study. MATERIALS AND METHODS: Patients undergoing endovascular therapy underwent baseline imaging, postprocedural angiography, and 24-hour follow-up imaging. The primary outcome was any intracranial hemorrhage observed on follow-up imaging. The secondary outcome was symptomatic hemorrhage. We assessed the relationship between hemorrhage occurrence and baseline patient characteristics, clinical course, and imaging factors: baseline ASPECTS, thrombus location, residual flow grade, collateralization, and clot burden score. Multivariable logistic regression with backward selection was used to adjust for relevant covariates. RESULTS: Of the 199 enrolled patients who met the inclusion criteria, 46 (23%) had an intracranial hemorrhage at 24 hours. On multivariable analysis, postprocedural hemorrhage was associated with pretreatment ASPECTS (OR, 1.56 per point lost; 95% CI, 1.12-2.15), clot burden score (OR, 1.19 per point lost; 95% CI, 1.03-1.38), and ICA thrombus location (OR, 3.10; 95% CI, 1.07-8.91). In post hoc analysis, clot burden scores of ≤3 (sensitivity, 41%; specificity, 82%; OR, 3.12; 95% CI, 1.36-7.15) and pretreatment ASPECTS ≤ 7 (sensitivity, 48%; specificity, 82%; OR, 3.17; 95% CI, 1.35-7.45) robustly predicted hemorrhage. Residual flow grade and collateralization were not associated with hemorrhage occurrence. Symptomatic hemorrhage was observed in 4 patients. CONCLUSIONS: Radiologic factors, early ischemia on CT, and increased CTA clot burden are associated with an increased risk of intracranial hemorrhage in patients undergoing endovascular therapy.

Health literacy and pap testing in insured women.

Several studies have found a link between health literacy and participation in cancer screening. Most, however, have relied on self-report to determine screening status. Further, until now, health literacy measures have assessed print literacy only. The purpose of this study was to examine the relationship between participation in cervical cancer screening (Papanicolaou [Pap] testing) and two forms of health literacy-reading and listening. A demographically diverse sample was recruited from a pool of insured women in Georgia, Massachusetts, Hawaii, and Colorado between June 2009 and April 2010. Health literacy was assessed using the Cancer Message Literacy Test-Listening and the Cancer Message Literacy Test-Reading. Adherence to cervical cancer screening was ascertained through electronic administrative data on Pap test utilization. The relationship between health literacy and adherence to evidence-based recommendations for Pap testing was examined using multivariate logistic regression models. Data from 527 women aged 40 to 65 were analyzed and are reported here. Of these 527 women, 397 (75 %) were up to date with Pap testing. Higher health literacy scores for listening but not reading predicted being up to date. The fact that health literacy listening was associated with screening behavior even in this insured population suggests that it has independent effects beyond those of access to care. Patients who have difficulty understanding spoken recommendations about cancer screening may be at risk for underutilizing screening as a result.

Trends in hospital admission for stroke in Calgary.

BACKGROUND: Stroke incidence has fallen since 1950. Recent trends suggest that stroke incidence may be stabilizing or increasing. We investigated time trends in stroke occurrence and in-hospital morbidity and mortality in the Calgary Health Region. METHODS: All patients admitted to hospitals in the Calgary Health Region between 1994 and 2002 with a primary discharge diagnosis code (ICD-9 or ICD-10) of stroke were included. In-hospital strokes were also included. Stroke type, date of admission, age, gender, discharge disposition (died, discharged) and in-hospital complications (pneumonia, pulmonary embolism, deep venous thrombosis) were recorded. Poisson and simple linear regression was used to model time trends of occurrence by stroke type and age-group and to extrapolate future time trends. RESULTS: From 1994 to 2002, 11642 stroke events were observed. Of these, 9879 patients (84.8%) were discharged from hospital, 1763 (15.1%) died in hospital, and 591 (5.1%) developed in-hospital complications from pneumonia, pulmonary embolism or deep venous thrombosis. Both in-hospital mortality and complication rates were highest for hemorrhages. Over the period of study, the rate of stroke admission has remained stable. However, total numbers of stroke admission to hospital have faced a significant increase (p=0.012) due to the combination of increases in intracerebral hemorrhage (p=0.021) and ischemic stroke admissions (p=0.011). Sub-arachnoid hemorrhage rates have declined. In-hospital stroke mortality has experienced an overall decline due to a decrease in deaths from ischemic stroke, intracerebral hemorrhage and sub-arachnoid hemorrhage. CONCLUSIONS: Although age-adjusted stroke occurrence rates were stable from 1994 to 2002, this is associated with both a sharp increase in the absolute number of stroke admissions and decline in proportional in-hospital mortality. Further research is needed into changes in stroke severity over time to understand the causes of declining in-hospital stroke mortality rates.

Risk factors for adverse drug events among nursing home residents.

BACKGROUND: In a prospective study of nursing home residents, we found adverse drug events (ADEs) to be common, serious, and often preventable. To direct prevention efforts at high-risk residents, information is needed on resident-level risk factors. METHODS: Case-control study nested within a prospective study of ADEs among residents in 18 nursing homes. For each ADE, we randomly selected a control from the same home. Data were abstracted from medical records on functional status, medical conditions, and medication use. RESULTS: Adverse drug events were identified in 410 nursing home residents. Independent risk factors included being a new resident (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.5-5.2) and taking anti-infective medications (OR, 4.0; CI, 2.5-6.2), antipsychotics (OR, 3.2; CI, 2.1-4.9), or antidepressants (OR, 1.5; CI, 1.1-2.3). The number of regularly scheduled medications was associated with increased risk of ADEs; the OR associated with taking 5 to 6 medications was 2.0 (CI, 1.2-3.2); 7 to 8 medications, 2.8 (CI, 1.7-4.7); and 9 or more, 3.3 (CI, 1.9-5.6). Taking supplements or nutrients was associated with lower risk (OR, 0.42; CI, 0.27-0.63). Preventable ADEs occurred in 226 residents. Independent risk factors included taking opioid medications (OR, 6.6; CI, 2.3-19.3), antipsychotics (OR, 4.0; CI, 2.2-7.3), anti-infectives (OR, 3.0; CI, 1.6-5.8), antiepileptics (OR, 2.2; CI, 1.1-4.5), or antidepressants (OR, 2.0; CI, 1.1-3.5). Scores of 5 or higher on the Charlson Comorbidity Index were associated with increased risk of ADEs (OR, 2.6; CI, 1.1-6.0). The number of regularly scheduled medications was also a risk factor: the OR for 7 to 8 medications was 3.2 (CI, 1.4-6.9) and for 9 or more, 2.9 (CI, 1.3-6.8). Residents taking nutrients or supplements were at lower risk (OR, 0.27; CI, 0.14-0.50). CONCLUSIONS: It is possible to identify nursing home residents at high risk of having an ADE. Particular attention should be directed at new residents, those with multiple medical conditions, those taking multiple medications, and those taking psychoactive medications, opioids, or anti-infective drugs.

Extraesophageal manifestations of gastroesophageal reflux.

BACKGROUND: Associations have been reported between gastroesophageal reflux and a variety of upper and lower respiratory tract conditions. Respiratory conditions and GER are common and would be expected to coexist in many patients. Whether there is a relationship between GER and these conditions and its nature remain controversial. The purpose of this paper is to review the relationship between GER and these conditions. METHODS: Searches of the 1966 to 2000 MEDLINE database were undertaken to identify appropriate studies. The terms gastroesophageal reflux, medical antireflux therapy, and antireflux surgery were combined with rhinitis, sinusitis, laryngitis, laryngeal stricture, croup, apnea, dental caries, aspiration pneumonia, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, COPD, chronic bronchitis, bronchiectasis and cough. RESULTS: Papers were identified that related any of the above respiratory conditions to gastroesophageal reflux or to antireflux therapy. Most suggested a causative relationship between GER and these conditions but only a few of the studies were controlled. Controlled studies demonstrate a strong association between GER and asthma and cystic fibrosis. CONCLUSIONS: A strong association between GER and some respiratory conditions has been demonstrated in controlled trials. It is uncertain whether the association is due to GER causing respiratory disease or vice versa. It is clear that further properly powered, controlled, randomized trials of the relationship between GER and antireflux therapy and respiratory disease need to be conducted.

The diffusion of a novel therapy into clinical practice: the case of sildenafil.

BACKGROUND: Erectile dysfunction is a common condition, yet in the past most affected men did not seek medical treatment. OBJECTIVE: To examine how sildenafil (Viagra), a new medication for the treatment of erectile dysfunction, has been incorporated into general medical practice. SUBJECTS AND METHODS: The study population consisted of all male members of a group-model Massachusetts health maintenance organization (HMO) whose first prescription for sildenafil was dispensed during the first 24 weeks of its availability through the HMO as a plan benefit (April 24, 1998, through October 8, 1998). Data collected on each member in the study population included age, specialty of the prescribing physician, initial dose, use of prior treatments for erectile dysfunction, receipt of medications known to predispose to impotence, filling of a second prescription for sildenafil, and concomitant medical conditions (including hypertension, ischemic heart disease, hyperlipidemia, diabetes mellitus, and history of radical prostatectomy). Cross tabulations and logistic regression models were constructed to evaluate the potential associations between filling a second prescription for sildenafil and other characteristics of sildenafil users. RESULTS: We identified 899 members who filled a first-time sildenafil prescription in the 24-week period of interest. The majority of sildenafil prescriptions that were filled for the first time (85%) occurred in the first 12 weeks of its availability. Most sildenafil users (84%) were between 45 and 74 years of age (average age, 61 years; age range, 23 to 90 years), and approximately 40% had documentation of prior treatment for erectile dysfunction. Use was highest among those aged 55 to 64 years, with almost 5% of all male HMO members in that age group having received at least 1 sildenafil prescription. Our cohort of sildenafil users was significantly more likely to have hypertension (P<.01), hyperlipidemia (P<.01), and diabetes mellitus (P<.01) than persons who participated in a widely publicized clinical trial of the medication. Prescribing physicians were predominantly primary care physicians (78% were internists, and 11% were family practitioners). More than 60% of sildenafil users filled a second prescription within 3 months of the first prescription; in multivariate analyses, factors associated with filling a second prescription included younger age and prior treatment for erectile dysfunction. CONCLUSIONS: Sildenafil was rapidly adopted into the clinical practice of primary care physicians for the treatment of erectile dysfunction in the managed care setting. The patients for whom the drug was prescribed in the general practice setting differed across many medical characteristics from study subjects who participated in clinical trials of the drug. Arch Intern Med. 2000;160:3401-3405.

Six-year effect of depressive symptoms on the course of physical disability in community-living older adults.

BACKGROUND: Late-life depression affects physical health and impedes recovery from physical disability. But whether milder symptoms that occur frequently in the general population increase the risk of developing a disability or decrease the likelihood of recovery remains unclear. OBJECTIVE: To examine the effect of mild symptoms of depression, assessed by a reduced version (10 items, ranging from 0-10) of the Center for Epidemiological Studies-Depression Scale, on the course of physical disability, assessed by items from the Katz Activities of Daily Living Scale, the Rosow-Breslau Functional Health Scale, and the Nagi Index. METHODS: A population-based longitudinal study was conducted, with 6 follow-up interviews of 3434 community-dwelling persons aged 65 years and older in East Boston, Mass. RESULTS: The likelihood of becoming disabled increased with each additional symptom of depression (for the Katz measure: odds ratio, 1.16 per symptom; 95% confidence interval, 1.13-1.19; for the Rosow-Breslau measure: odds ratio, 1.14; 95% confidence interval, 1.11-1.16; and for the Nagi measure: odds ratio, 1.17; 95% confidence interval, 1.14-1.19). As the number of depressive symptoms increased, the likelihood of recovering from a physical disability decreased (for the Katz measure: odds ratio, 0.96; 95% confidence interval, 0.93-0.99; for the Rosow-Breslau measure: odds ratio, 0.86; 95% confidence interval, 0.84-0.89; and for the Nagi measure: odds ratio, 0.89; 95% confidence interval, 0.87-0.91). This effect was not accounted for by age, sex, level of educational attainment, body mass index, or chronic health conditions. CONCLUSION: Mild depressive symptoms in older persons (those aged > or =65 years) are associated with an increased likelihood of becoming disabled and a decreased chance of recovery, regardless of age, sex, and other factors that contribute to physical disability.

Incidence and preventability of adverse drug events in nursing homes.

PURPOSE: Adverse drug events, especially those that may have been preventable, are among the most serious concerns about medication use in nursing homes. We studied the incidence and preventability of adverse drug events and potential adverse drug events in nursing homes. METHODS: We performed a cohort study of all long-term care residents of 18 community-based nursing homes in Massachusetts during a 12-month observation period. Potential drug-related incidents were detected by stimulated self-report by nursing home staff and by periodic review of the records of nursing home residents by trained nurse and pharmacist investigators. Each incident was classified by 2 independent physician-reviewers, using a structured implicit review process, by whether or not it constituted an adverse drug event or potential adverse drug event (those that may have caused harm, but did not because of chance or because they were detected), by the severity of the event (significant, serious, life-threatening, or fatal), and by whether it was preventable. Examples of significant events included nonurticarial rashes, falls without associated fracture, hemorrhage not requiring transfusion or hospitalization, and oversedation; examples of serious events included urticaria, falls with fracture, hemorrhage requiring transfusion or hospitalization, and delirium. RESULTS: During 28,839 nursing home resident-months of observation in the 18 participating nursing homes, 546 adverse drug events (1.89 per 100 resident-months) and 188 potential adverse drug events (0.65 per 100 resident-months) were identified. Of the adverse drug events, 1 was fatal, 31 (6%) were life-threatening, 206 (38%) were serious, and 308 (56%) were significant. Overall, 51% of the adverse drug events were judged to be preventable, including 171 (72%) of the 238 fatal, life-threatening, or serious events and 105 (34%) of the 308 significant events (P < 0.001). Errors resulting in preventable adverse drug events occurred most often at the stages of ordering and monitoring; errors in transcription, dispensing, and administration were less commonly identified. Psychoactive medications (antipsychotics, antidepressants, and sedatives/hypnotics) and anticoagulants were the most common medications associated with preventable adverse drug events. Neuropsychiatric events were the most common types of preventable adverse drug events. CONCLUSIONS: Adverse drug events are common and often preventable in nursing homes. More serious adverse drug events are more likely to be preventable. Prevention strategies should target the ordering and monitoring stages of pharmaceutical care.

Knowledge, patterns of care, and outcomes of care for generalists and specialists.

OBJECTIVE: To critically evaluate the differences between generalist physicians and specialists in terms of knowledge, patterns of care, and clinical outcomes of care. METHODS: English-language articles (January 1981 to January 1998) were identified through a Medline search and examination of bibliographies of identified articles. Systematic evaluation of articles relevant to adult medicine that had a direct comparison between generalist physicians and specialists in terms of knowledge relative to widely accepted standards of care, patterns of care (including use of medications, ancillary services, procedures, and resource utilization), and outcomes of care was performed. MAIN RESULTS: In many survey studies, specialists were reported to be more knowledgeable about conditions encompassed within their specialty. In terms of overall practice patterns, specialists practicing in their area of expertise were more likely to use medications associated with improved survival and to comply with routine health maintenance screening guidelines; they used more resources including diagnostic tests, procedures, and longer hospital stays. In the limited number of studies examining the care of patients with acute myocardial infarction, acute nonhemorrhagic stroke, and asthma, specialists had superior outcomes compared with generalists. CONCLUSIONS: There is evidence in the literature suggesting differences between specialists and generalists in terms of knowledge, patterns of care, and clinical outcomes of care for a broad range of diseases. In published studies, specialists were generally more knowledgeable about their area of expertise and quicker to adopt new and effective treatments than generalists. More research is needed to examine whether these patterns of care translate into superior outcomes for patients. Further work is also needed to delineate the components of care for which generalists and specialists should be responsible, in order to provide the highest quality of care to patients while most effectively utilizing existing physician manpower.

Misclassification and under-reporting of acute myocardial infarction by elderly persons: implications for community-based observational studies and clinical trials.

We investigated the accuracy of self-report of hospitalization for acute myocardial infarction (MI) by elderly persons in a community-based prospective study. Among 3809 persons aged 65 years or older followed up for 6 years, self-reported hospitalization for MI was validated by review of primary records and Medicare diagnoses. Among 147 who self-reported MI and for whom hospital records were available, the diagnosis was confirmed in 79 (54%). Myocardial infarction was not a reason for hospitalization among the remaining 68 participants; misclassification with other cardiovascular diagnoses was common. Medicare diagnosis correlated well with primary hospital records. Using Medicare diagnoses as the standard, the diagnosis of MI was confirmed in 53% of self-reports; the sensitivity and specificity of self-report were 51% and 98%, respectively. False-negative reporting was common because only half of hospitalizations for MI were reported. Self-report of hospitalization for MI by elderly persons in the community may be unreliable for ascertaining trends in cardiovascular diseases.

The renal effects of nonsteroidal anti-inflammatory drugs in older people: findings from the Established Populations for Epidemiologic Studies of the Elderly.

OBJECTIVE: To determine whether older people who use nonsteroidal anti-inflammatory agents (NSAIDs) have increased levels of blood urea nitrogen (BUN), serum creatinine, and BUN:serum creatinine ratio. DESIGN: Cross-sectional, secondary data analysis. SETTING: Older people living in the communities of East Boston, MA, New Haven, CT, and Washington and Iowa Counties, Iowa. PARTICIPANTS: A total of 4099 people aged 70 years or older who were participants in the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly project, had survived to the 6-year follow-up interview and had consented to the blood drawing. MEASUREMENTS: We assessed use of the NSAIDs at the 3- and 6-year interviews through a drug inventory and visual review of medication containers. Markers of renal function assessed through analysis of blood samples drawn at the time of the interview included BUN and creatinine. RESULTS: Fifteen percent of the cohort reported use of NSAIDs during the 2 weeks preceding the 6-year interview. Controlling for age, sex, and a range of potential confounding variables, NSAID users had significant prevalence odds ratios of 1.9 (95% confidence interval (CI), 1.5-2.3) for being in the highest quartile of BUN (>23), 1.3 (CI 1.1-1.7) for the highest quartile of serum creatinine (> or =1.4), and 1.7 (CI 1.4-2.1) for the highest quartile of the BUN:creatinine ratio (> or = 19.4). Chronic NSAID users (those who reported NSAID use at both the 3-year and 6-year interviews) accounted for the increased risk of high serum creatinine levels. CONCLUSION: Community-dwelling older people who use NSAIDs tend to have higher levels of common laboratory markers of renal dysfunction. This hypothesis requires further testing in prospective cohort studies designed a priori to evaluate these issues.

Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease.

Oxidative stress may play a role in neurologic disease. The present study examined the relation between use of vitamin E and vitamin C and incident Alzheimer disease in a prospective study of 633 persons 65 years and older. A stratified random sample was selected from a disease-free population. At baseline, all vitamin supplements taken in the previous 2 weeks were identified by direct inspection. After an average follow-up period of 4.3 years, 91 of the sample participants with vitamin information met accepted criteria for the clinical diagnosis of Alzheimer disease. None of the 27 vitamin E supplement users had Alzheimer disease compared with 3.9 predicted based on the crude observed incidence among nonusers (p = 0.04) and 2.5 predicted based on age, sex, years of education, and length of follow-up interval (p = 0.23). None of the 23 vitamin C supplement users had Alzheimer disease compared with 3.3 predicted based on the crude observed incidence among nonusers (p = 0.10) and 3.2 predicted adjusted for age, sex, education, and follow-up interval (p = 0.04). There was no relation between Alzheimer disease and use of multivitamins. These data suggest that use of the higher-dose vitamin E and vitamin C supplements may lower the risk of Alzheimer disease.

Introducing managed care to the medical school curriculum: effect on student attitudes.

In order to assess the effect of clinical training and didactic instruction on medical student attitudes toward managed care, we conducted a survey of all medical students at the midpoint of their third year clerkships at the University of Massachusetts Medical School. The students were exposed to clinical training in managed care settings and a 2-day required course on the principles underlying managed care. The main outcome measures were student attitudes toward the concepts of managed care, managed care organizations, and future careers in managed care. Students also assessed the attitudes of medical faculty toward managed care. Attitudes of students with previous clinical training in managed care settings did not differ from those of students without such exposure toward the concepts underlying managed care or managed care organizations and were less positive about careers in managed care. Student responses before and after the 2-day course on managed care demonstrated that attitudes moved in a significantly positive direction. Seventy-one percent of students reported that the opinions they had heard from medical faculty about managed care were negative. Preparing medical students to practice medicine effectively in managed care settings will require focused attention on managed care issues in the medical school curriculum and the combined efforts of academic health centers and managed care organizations.

Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons.

OBJECTIVE: To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the epsilon4 allele. DESIGN: Community-based cohort study. SETTING: East Boston, Mass. PARTICIPANTS: A random sample of 578 community residents aged 65 years and older free of AD. MAIN OUTCOME MEASURE: Clinical diagnosis of AD by uniform, structured evaluation. RESULTS: The increased risk of AD associated with the presence of the epsilon4 allele was less than that found in most family and case-control studies. Persons with the epsilon4/epsilon4 or epsilon3/epsilon4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the epsilon3/epsilon3 genotype. The epsilon4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the epsilon4 allele on risk of AD did not appear to vary with age. CONCLUSIONS: The apolipoprotein E epsilon4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.

Aspirin use and cognitive function in the elderly.

Decline in cognitive function in the elderly is common and represents a major clinical and public health concern. Aspirin may reduce the decline in cognitive function by influencing multi-infarct dementia, but data are sparse. The East Boston Senior Health Project is a population-based cohort study that enrolled 3,809 community-dwelling residents aged 65 years and older in 1982-1983 and followed them with home visits every 3 years until 1988-1989. Trained interviewers assessed cognitive function by using the Short Portable Mental Status Questionnaire and assessed medication use, including over-the-counter drugs. Response to the Short Portable Mental Status Questionnaire was scored as high, medium, or low, and decline was defined as transition to a lower category. Participants who used drugs containing aspirin in the 2 weeks prior to the interview were classified as aspirin users. Multiple logistic regression was used to obtain adjusted odds ratios and their 95% confidence intervals for decline of cognitive function. The estimating equation approach was used to adjust the standard errors for repeated measurements. Aspirin users had an odds ratio for cognitive decline of 0.97 (95% confidence interval 0.82-1.15). Low frequency of aspirin use (less than daily) was associated with an odds ratio of 0.87 (95% confidence interval 0.69-1.09). Although no substantial effect was observed, the data are also compatible with a modest benefit of aspirin, especially with intermittent use, on decline of cognitive function. Concern about small residual biases from self-selection or confounding suggests that randomized trials will be necessary to provide definitive data on this question.