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Biomedical subjects

E B Larson

Publications and source records attributed to E B Larson.

At least 19 recordsLinked to original sources
PubMed1992

Disease, level of impact, and quality of research methods. Three dimensions of clinical efficacy assessment applied to magnetic resonance imaging.

Assessment of the clinical efficacy of diagnostic imaging technologies frequently involves reviews of published research. Reports may be classified in three dimensions; by disease, by type of assessment, and by the quality of research methods. The disease dimension describes the condition or conditions shown by an imaging technique. The assessment dimension spans five levels: technical capacity, diagnostic accuracy, diagnostic impacts, therapeutic impacts, and patient outcome impacts. The methods quality dimension can be expressed as four levels: excellent, good, fair or poor. An important interaction exists: the level of efficacy addressed by a research project dictates which methodologic procedures are important. For example, randomization is important only when a research report addresses the levels of therapeutic and patient outcome impacts. The authors suggest that classification of studies according to the three preceding dimensions maps the breadth (across diseases), depth (across levels of clinical efficacy), and quality of the assessment of complex imaging technologies. Such a map should help participants in technology assessment define the progress they have made. The classification strategy as applied to the clinical efficacy assessment of magnetic resonance imaging (MRI) for neuroradiology is illustrated.

Humans↗
PubMed1992

Trends in the utilization of mammography in Washington state and British Columbia: relation to stage of diagnosis and mortality.

To compare the utilization of an imaging technology in the United States and Canada and its effect on clinical outcomes, trends in the utilization of mammography among women aged 50 to 75 years from 1984 through 1988 in Washington State and British Columbia were examined. Also compared were trends in the stage at time of diagnosis of invasive breast cancer and mortality due to breast cancer in the two regions. Annual mammography use increased in both regions, but the proportion of women examined was consistently two to three times higher in Washington than in British Columbia (43% vs 16% in 1988). Although there was no difference in mortality trends, the proportion of women diagnosed with localized disease in Washington increased each year (from 52% to 64%, P less than .001), while in British Columbia it remained unchanged at approximately 56%. Results of this study suggest that differences in utilization were influenced by clinical policies, the degree to which these policies were promoted, reimbursement, and the organization of radiology services.

Aged↗
PubMed1992

The cost of institutional care in Alzheimer's disease: nursing home and hospital use in a prospective cohort.

OBJECTIVE: To assess the nursing home and hospital use of patients with Alzheimer's Type Dementia. DESIGN: A prospective cohort study of 126 patients entered into an Alzheimer's disease registry after diagnosis at a university hospital clinic between 1980 and 1982. Only four patients were in nursing homes at enrollment. MEASUREMENTS AND MAIN RESULTS: Data regarding nursing home use came from the registry and the individual nursing homes themselves. Hospital-use data were obtained using Medicare claims files. Follow-up was obtained on 123 patients (98%). Eighty-five (69%) had died by July 1, 1989. Three-quarters of the cohort (92) eventually resided in nursing homes. The median nursing home length of stay was 2.75 years (mean 2.95, 95% CI = 2.5, 3.4), over 10 times the national median length of stay for all diagnoses. Based on prevailing rates in the region, nursing home charges for the cohort were estimated to be between $4.3 and $6.4 million ($35,000-$52,000 per patient). During the 5-year period 1983-1988, 69 patients filed Part A (hospital) claims to Medicare for 76 admissions and 616 inpatient days. Part A Medicare reimbursement for the cohort totaled $460,000 over 5 years ($3,700 per patient), an expenditure comparable to what a random Medicare cohort might incur. CONCLUSIONS: The combination of a high rate of nursing home entry and lengthy stays makes long-term care the largest determinant of the cost of care in Alzheimer's disease. While Alzheimer's Type Dementia undoubtedly has profound indirect costs, this study demonstrates that the direct institutional costs alone are considerable.

Aged↗
PubMed1992

Cognitive impairment: dementia and Alzheimer's disease.

The importance of dementia, a syndrome of global cognitive impairment, has gained widespread recognition in the past two decades. The most common cause, Alzheimer's disease, may be the single greatest source of dysfunction among persons over age 85. The disease, distinct from normal aging, is progressive, has a highly variable course, and can have tremendous impact on families. Duration of symptoms averages eight to ten years from onset, four to five years from diagnosis. Diagnosis is often delayed, because of the insidious nature of the illness. Prevalence and incidence rates may vary severalfold between different studies. One consistent finding is the dramatic increase with age; prevalence rates are 25-48% for persons over age 85. The two most consistent risk factors for AD are age and positive family history. Another likely risk factor is head trauma. Alzheimer's disease is almost certainly due to heterogeneous causes. Biologic understanding of AD is primarily based on study of distinctive pathologic changes in the brain. Increasingly well-characterized pathologic changes precede the clinical manifestation of disease. Ultimately, the pathologic cause of AD is loss of neurons and neuronal connections in the brain, especially in the frontal and parietal association neocortex. Many systems are involved, but the most affected system is the cholinergic system, followed by the noradrenergic and serotonergic neurotransmitter systems. Drug treatment and other intervention strategies to prevent or delay progression of the disease have been limited, primarily because so little is known about the cause or risk factors for the disease. Current palliative treatments are attempts to minimize the morbidity of abnormal behaviors and medical complications associated with dementia. Ideally, treatment would either involve replacement therapy or drugs, which prevent or delay the pathologic changes that occur in AD. Two of the more promising experimental therapeutic attempts involve interruption of the pathogenetic events involving beta-amyloid and its precursor proteins and administration of NGF. Public health attempts at risk factor reduction are clearly premature. The next decade or two will likely witness improved understanding of the pathogenesis of Alzheimer's disease. Epidemiologic study will contribute to our knowledge of pathogenesis and may reveal heretofore unrecognized and, hopefully, modifiable risk factors. Social and clinical strategies to deal with a disease of such immense importance also needs development and evaluation. The public's interest in this disease is intense, and it looks to the scientific community for progress in understanding and managing this often tragic illness.

Aged↗
PubMed1992

Effects of physical activity on health status in older adults. II. Intervention studies.

This review has focused on a specific part of the relationship of exercise to health. The overall evidence supporting the health benefits of exercise is substantial and has been critically reviewed recently (18, 94). Thus, the United States Preventive Services Task Force recommends that all adults exercise regularly (94). The conclusions summarized below regarding older adults do not affect this basic recommendation. There is solid evidence that exercise can improve measures of fitness in older adults, particularly strength and aerobic capacity. These exercise effects occur in chronically ill adults, as well as in healthy adults. Because physical fitness is a determinant of functional status, it is logical to ask whether exercise can prevent or improve impairments in functional status in older adults. The evidence that exercise improves functional status is promising, but inconclusive. Problems with existing studies include a lack of randomized controlled trials, a lack of evidence that effects of exercise can be sustained over long periods of time, inadequate statistical power, and failure to target physically unfit individuals. Existing studies suggest that exercise may produce improvements in gait and balance. Arthritis patients may experience long-term functional status benefits from exercise, including improved mobility and decreased pain symptoms. Nonrandomized trials suggest exercise promotes bone mineral density and thereby decreases fracture risk. Recent studies have generally concluded that short-term exercise does not improve cognitive function. Yet the limited statistical power of these studies does not preclude what may be a modest, but functionally meaningful, effect of exercise on cognition. Future research, beyond correcting methodologic deficiencies in existing studies, should systematically study how functional status effects of exercise vary with the type, intensity, and duration of exercise. It should address issues in recruiting functionally impaired older adults into exercise studies, issues in promoting long-term adherence to exercise, and whether the currently low rate of exercise-related injuries in supervised classes can be sustained in more cost-effective interventions that require less supervision.

Activities of Daily Living↗
PubMed1992

Increased platelet membrane fluidity as a diagnostic marker for Alzheimer's disease: a test in population-based cases and controls.

To test whether increased platelet membrane fluidity as measured by decreased steady state fluorescence anisotropy (rs) of diphenylhexatriene is a biologic/diagnostic marker for Alzheimer's disease (AD), we enrolled 95 clinically diagnosed, probable AD cases from our Alzheimer's Disease Patient Registry and 133 control subjects of similar age and sex randomly selected from the same population base as the cases. We measured rs in platelet membranes following published assay procedures. Laboratory personnel and investigators were blind to the identity of the samples; cases and controls were assayed in random order. Our analyses showed that the distributions of rs values were unimodal and similar for cases and controls. The overall mean differences (control mean-case mean) for the two established assay methods tested were 0.0011 and 0.0003. A nonparametric Wilcoxon rank sum test also showed no difference between cases and controls. Multivariate analysis adjusted for the significant effects of the processing date and analysis platelet recovery led to a final model with the adjusted mean difference of 0.0007 for the principal method. Increased platelet membrane fluidity is not an antemortem diagnostic or biologic marker for AD in our population.

Aged↗
PubMed1992

Diagnosis of lumbar spinal stenosis in adults: a metaanalysis of the accuracy of CT, MR, and myelography.

We undertook a literature synthesis of CT, MR, and myelographic studies to evaluate what is known about the diagnostic accuracy of these imaging tests for the diagnosis of lumbar spinal stenosis in adults without prior surgery. From 116 possibly relevant studies, we reviewed 14 articles that included cases of spinal stenosis with a reference standard other than the imaging tests of interest. Of the studies we reviewed, two involved only MR, nine only CT, and three used both; six studies included myelography. Rating categories of A, B, C, or D were assigned for the quality of research methods used to estimate diagnostic accuracy. All studies received either a C or D rating. Common methodologic problems were failure to assemble a representative cohort for study, small sample size, and failure to maintain independence between image readings and reference standards. Sensitivity ranged from 0.81 to 0.97 for MR, from 0.70 to 1.0 for CT, and from 0.67 to 0.78 myelography. Studies varied greatly in case selection, definition of test and disease categories, and geographic locale, so no pooled estimates could be derived. In asymptomatic patients, abnormal findings appeared on CT or MR in 4-28% of cases and were more common in the elderly. Published studies of the value of CT and MR for the diagnosis of lumbar stenosis lack methodologic rigor and do not permit strong conclusions about the relative diagnostic accuracies of these procedures. For the present, the choice between MR or CT depends on issues such as costs, reimbursements, access to equipment, skill of radiologists, and patient safety. Better studies will be needed to document claims for improvements in imaging accuracy as MR technologies evolve. These studies should emphasize larger sample sizes, more attention to research designs that avoid methodologic biases, and the contribution of imaging diagnoses to ultimate clinical outcome.

Evaluation Studies as Topic↗
PubMed1992

The effectiveness of cerebral imaging in the diagnosis of chronic headache.

OBJECTIVE: The increasing availability of high-resolution cerebral imaging scanners has fueled enthusiasm for their use to "rule out" brain tumor and other serious neurologic conditions in patients with headache. The effectiveness of this practice, however, has not been tested since the advent of newer scanning equipment. Our objective was to measure the usefulness of cerebral imaging in patients with chronic isolated headache. DESIGN: A retrospective study with a 15- to 27-month follow-up period. SETTING: A group-model health maintenance organization. PATIENTS: Adult patients, 100,800, in a health maintenance organization and an enriched sample of 63 patients with neurosurgical conditions from other health maintenance organization hospitals. RESULTS: During 1990, 1083 cerebral computed tomographic scans were performed on 863 adults (0.9% of health maintenance organization adults). Eighty-nine patients were scanned for chronic isolated headache; none of the scans provided important new information (95% confidence interval, 0%, 3%). Long-term patient follow-up confirmed that this low yield could not be attributed to diagnostic work-up bias. Further attempts to support a policy of imaging patients with isolated headache were also unsuccessful. Review of an enriched sample of patients with malignant brain tumor and patients requiring craniotomy for other reasons (n = 40) demonstrated that no patient had headache alone at the time of diagnosis (95% confidence interval, 0%, 8%) and that only 5% (95% confidence interval, 0%, 12%) of these patients sought medical attention for headache alone. Sampling a second enriched sample of patients who were referred from other hospitals (n = 63) because of conditions requiring neurosurgical procedures demonstrated that only 6% of patients presented with chronic isolated headache alone (95% confidence interval, 0%, 12%). Uncertainty regarding the appropriateness of imaging patients with headache was illustrated by the extreme interphysician variability of this practice. CONCLUSION: Our study demonstrates the large potential cost and low (although not zero) yield associated with nonselectively imaging patients with chronic isolated headache.

Adult↗
PubMed1992

Benefits of exercise for older adults. A review of existing evidence and current recommendations for the general population.

Currently available data are of variable rigor and from a variety of sources, yet they do support several conclusions about the potential value of exercise for whole groups of elderly persons. (1) Exercise of moderate intensity may benefit many elderly persons in numerous and complementary ways (e.g., cardiovascular status, fracture risk, functional ability, and mental processing). (2) There are few complications associated with such increases in activity. Indeed, a remarkable aspect of research on exercise in the elderly has been the virtual absence of reports of serious cardiovascular or musculoskeletal complications in any published trials. Cardiac rehabilitation programs, enrolling many persons over 65 years of age with known coronary artery disease, also report few major cardiovascular complications. Thus, exercise should be viewed as safe for most older adults. (3) Exercise in the elderly probably needs to be tailored, and when possible, individualized, with the specific objectives of the person or group in mind. Some benefits are probably related to the intensity of exercise (e.g., cardiovascular disease), others due to the type of exercise (weight-bearing versus nonweight-bearing for osteoporosis, or racket sports for hand-eye coordination), and still others possibly relate to the setting in which exercise occurs (social-psychological benefits). (4) The authors believe the known physiologic effects of exercise on age-related changes and existing clinical research support the general notion that vigorous weight-bearing exercises such as walking are the safest, cheapest, easiest, and most widely beneficial for the average senior. (5) Research has yet to define good ways by which to stimulate large numbers of sedentary elderly persons to exercise regularly. The potential and complementary benefits appear to be great enough to justify widespread efforts at the community and individual level, however.

Activities of Daily Living↗
PubMed1992

A critical appraisal of ticlopidine, a new antiplatelet agent. Effectiveness and clinical indications for prophylaxis of atherosclerotic events.

BACKGROUND: Recommendations are broadening for the prophylaxis of atherosclerotic disorders, but aspirin is the only widely used agent. Ticlopidine hydrochloride, a new antiplatelet medication, has recently been approved for prescription in North America. We reviewed the major clinical trials of ticlopidine and derived guidelines for its use. METHODS: Studies of ticlopidine were sought through MEDLINE for 1980 to 1990 and through bibliographies of retrieved articles. All published, randomized trials of ticlopidine were appraised if they reported major morbidity and mortality as primary end points. All eligible studies were formally reviewed by an expert panel according to published principles for critical appraisal of the medical literature. Both benefits and risks were quantified. RESULTS: Four randomized trials reported major clinical end points. In these, ticlopidine was more effective than placebo for preventing recurrences after completed stroke; was more effective than aspirin for patients with transient ischemic attacks and partial strokes; and reduced vascular death and nonfatal myocardial infarction in an open trial among patients with unstable angina. For patients with intermittent claudication ticlopidine, was not significantly better than placebo for preventing myocardial infarction or stroke. Side effects were more common with ticlopidine than with aspirin or placebo. CONCLUSIONS: Ticlopidine should be prescribed in place of aspirin for stroke prophylaxis or unstable angina if the patient is unable to tolerate aspirin. Ticlopidine may also benefit patients who experience new ischemic events while taking aspirin or, probably, patients with peripheral vascular disease. A complete blood cell count should be performed every 2 weeks during the first 3 months of therapy to check for leukopenia.

Arteriosclerosis↗
PubMed1991

Changes over time in the knowledge base of practicing internists.

OBJECTIVE: To determine factors affecting the knowledge base of practicing internists. DESIGN: An 82-item multiple-choice examination with questions from the 1988 American Board of Internal Medicine (ABIM) certifying examination was used to assess the knowledge base of 289 internists. SETTING AND PARTICIPANTS: Participants were selected from among practicing internists in New York, New Jersey, and Pennsylvania who had received ABIM certification 5 to 15 years previously. RESULTS: significant inverse correlation (r = -.30) was found between examination scores and the number of years elapsed since certification. Knowledge declined sharply within 15 years of certification. In addition, procedure-oriented subspecialists (cardiologists and gastroenterologists) had lower scores than other internists in this examination of general medical knowledge. Multivariate analyses showed that independent variables that predicted test performance were initial ABIM certifying examination score, time elapsed since certification, subspecialty classification, medical school type, and residency type. CONCLUSIONS: These results support the recent decision for time-limited certification of internists and raise questions related to content and standard setting for recertification examinations.

Certification↗
PubMed1991

Are there clinical and epidemiological differences between familial and non-familial Alzheimer's disease?

To determine whether there are clinical and epidemiological differences between familial and non-familial Alzheimer's disease, we studied 151 patients with the clinical diagnosis of Dementia of the Alzheimer Type (DAT). Eighty-four index patients (56%) had at least one relative with reported DAT-type memory loss; the remaining 67 did not. For comparison, patients with a positive family history were grouped into a suspected familial DAT (FDAT), and those with a negative family history were grouped into a suspected non-familial DAT (NFDAT). There were no significant differences between FDAT and NFDAT patients with respect to age of symptom onset, survival time, rate of cognitive decline, motor function, behavioral signs or symptoms, head trauma, thyroid dysfunction, maternal age, or birth order. There were no significant differences between pedigrees of FDAT and NFDAT patients in respect to the prevalence of Down's syndrome or age of mortality. To examine a more "familial" set of FDAT patients, an FDAT subgroup (F2DAT) consisting of 33 index patients with two or more affected relatives with DAT-type memory loss was compared to the 67 NFDAT patients in a similar analysis. No significant differences were found. However, NFDAT index patients had a higher reported prevalence of head trauma than those patients in the F2DAT subgroup (NFDAT 22%, F2DAT 7%, OR = 4.2, CI = 0.9-20.0, P = 0.08). Thus severe head trauma may be a more important etiological factor in the non-familial form of DAT. To better examine this tendency, future studies should be conducted utilizing a larger number of pedigrees and familial criteria which account for the number of persons at risk and the age at onset of disease.

Aged↗
PubMed1991

Effect of education on the mini-mental state examination as a screening test for dementia.

We studied whether Mini-Mental State Examination (MMSE) norms for detecting dementia in elderly outpatients vary according to educational attainment. Subjects were 109 elderly outpatients with Alzheimer's dementia and 100 non-demented outpatient controls. Receiver operating characteristics (ROC) of the MMSE were examined among three strata of educational attainment: middle school, high school, and college/graduate school. MMSE ROC curve areas were .95-.96 in the three educational strata. Assuming a dementia prevalence of 10%-30%, the most accurate lower limits of normal for MMSE scores and their attendant sensitivities and specificities were 21 for middle school (.82/.94), 23 for high school (.79/.97), and 24 for college/graduate school (.83/1.00) attainment. These norms accurately classified over 90% of subjects in all three educational strata. We conclude that education-specific norms optimize performance of the MMSE as a screening test for Alzheimer's dementia in elderly outpatients.

Aged↗
PubMed1991

APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease.

The amyloid precursor protein (APP) gene codes for the precursor to the beta-protein found in the amyloid deposits of Alzheimer disease (AD). Recently Goate et al. identified in codon 717 of this gene a missense mutation which segregates with AD in a familial AD (FAD) kindred. The same mutation was also found in affected subjects from a second FAD family but not in other FAD families or in normal controls. The following work was undertaken to determine the frequency of the codon 717 mutation in FAD and nonfamilial AD cases and in normal controls. We tested 76 FAD families, 127 "sporadic" AD subjects, 16 Down syndrome cases, and 256 normal controls for this mutation, and none were positive. We also tested for the APP codon 693 mutation associated with hereditary cerebral hemorrhage with amyloidosis-Dutch type, for PRIP gene missense mutations at codons 102, 117, and 200, and for the PRIP insertion mutations which are associated with Creutzfeld-Jakob disease and Gerstmann-Straussler Scheinker syndrome. No examples of these mutations were found in our population. Thus these APP and PRIP mutations are rare in both FAD and nonfamilial AD.

Adult↗
PubMed1991

Acetazolamide or dexamethasone use versus placebo to prevent acute mountain sickness on Mount Rainier.

Eighteen climbers actively ascended Mount Rainier (elevation 4,392 m) twice during a randomized, double-blind, concurrent, placebo-controlled, crossover trial comparing the use of acetazolamide, 250 mg, dexamethasone, 4 mg, and placebo every 8 hours as prophylaxis for acute mountain sickness. Each subject was randomly assigned to receive placebo during one ascent and one of the active medications during the other ascent. Assessment of acute mountain sickness was performed using the Environmental Symptoms Questionnaire and a clinical interview. At the summit or high point attained above base camp, the use of dexamethasone significantly reduced the incidence of acute mountain sickness and the severity of symptoms. Cerebral and respiratory symptom severity scores for subjects receiving dexamethasone (0.26 +/- 0.16 and 0.20 +/- 0.19, respectively) were significantly lower than similar scores for both acetazolamide (0.80 +/- 0.80 and 1.20 +/- 1.05; P = 0.25) and placebo (1.11 +/- 1.02 and 1.45 +/- 1.27; P = .025). Neither the use of dexamethasone nor that of acetazolamide measurably affected other physical or mental aspects. Compared with placebo, dexamethasone appears to be effective for prophylaxis of symptoms associated with acute mountain sickness accompanying rapid ascent. The precise role of dexamethasone for the prophylaxis of acute mountain sickness is not known, but it can be considered for persons without contraindications who are intolerant of acetazolamide, for whom acetazolamide is ineffective, or who must make forced, rapid ascent to high altitude for a short period of time with a guaranteed retreat route.

Acetazolamide↗