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Biomedical subjects

H Feldman

Publications and source records attributed to H Feldman.

At least 37 records · Page 2Linked to original sources

The diagnosis of "mixed" dementia in the Consortium for the Investigation of Vascular Impairment of Cognition (CIVIC).

If vascular risk factors are risk for Alzheimer's disease (AD), and if "pure" vascular dementia (VaD) is less common than has been thought, what do we make of the diagnosis of mixed dementia? We report characteristics of those with mixed dementia in a prospective, seven center, clinic-based Canadian study. Of 1,008 patients, 372 were diagnosed with AD, 149 with vascular cognitive impairment (VCI) including 76 with mixed AD/VaD, and 82 with other types of dementia. The mean age of patients with mixed AD/VaD was 78.0 +/- 7.6 years; 49% were female. These proportions differed significantly between dementia diagnosis subgroup (p < 0.001) showing a trend which is evident in all comparisons--AD/VaD patients fall in between AD and VaD. Vascular risk factors were present significantly more often in mixed AD/VaD than in AD (p < 0.001). More mixed AD/VaD (20%) than AD patients (4%) had focal signs, compared with 38% of those with vascular dementia and 12% with other types of dementia. Between the initial clinical diagnosis and the final diagnosis (which utilized neuroimaging and neuropsychological data) AD/VaD was the least stable diagnosis. Neuroimaging of ischemic lesions was the most common reason for reassignment from AD to the mixed AD/VaD diagnosis (17 cases). These data suggest that an operational definition of mixed AD/VaD can be proposed on presentation and clinical/radiographic findings, but indifferent to vascular risk factors. The concept of mixed dementia should be extended to include vascular dementia in combination with dementias, other than Alzheimer's disease.

Aged↗

The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia.

OBJECTIVE: To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians toward the recognition, assessment and management of dementing disorders and to disseminate and evaluate the impact of these statements and guidelines built on these statements. OPTIONS: Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral, management of complications (especially behavioural problems and depression) and use of cognitive enhancing agents. POTENTIAL OUTCOMES: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations; neuroimaging and referrals; and appropriate use of cognitive enhancing agents. EVIDENCE: Authors of each background paper were entrusted to perform a literature search, discover additional relevant material, including references cited in retrieved articles, consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based on this evidence, consensus statements were developed by a group of experts, guided by a steering committee of 8 individuals, from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems. VALUES: Recommendations have been developed with particular attention to the context of primary care, and are intended to support family physicians in their ongoing assessment and care of patients with dementia. BENEFITS HARM AND COSTS: Potential for improved clinical care of people with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. RECOMMENDATIONS: Forty-eight recommendations are offered that address the following aspects of dementia care: early recognition; importance of careful history and examination in making a positive diagnosis; essential laboratory tests; rules for neuroimaging and referral; disclosure of diagnosis; importance of monitoring and providing support to caregivers; cultural aspects; detection and treatment of depression; observation and management of behavioural disturbances; detection and reporting of unsafe motor vehicle driving; genetic factors and opportunities for preventing dementia; pharmacological treatment with particular emphasis on cognitive enhancing agents. VALIDATION: Four other sets of consensus statement or guidelines have been published recently. These recommendations are generally congruent with our own consensus statements. The consensus statements have been endorsed by relevant bodies in Canada.

Automobile Driving↗

Seizure control and mortality in epilepsy.

Mortality rates are increased among people with epilepsy, and may be highest in those with uncontrolled seizures. Because epilepsy surgery eliminates seizures in some people, we used an epilepsy surgery population to examine how seizure control influences mortality. We tested the hypothesis that patients with complete seizure relief after surgery would have a lower mortality rate than those who had persistent seizures. Three hundred ninety-three patients who had epilepsy surgery between January 1986 and January 1996 were followed after surgery to assess long-term survival; 347 had focal resection or transection, and 46 had anterior or complete corpus callosotomy. A multivariate survival analysis was performed, contrasting survival in those who had seizure recurrence with survival of those who remained seizure free. Standardized mortality ratios and 95% confidence intervals were calculated. Overall, seizure-free patients had a lower mortality rate than those with persistent seizures. This was true for the subset of patients with localized resection or multiple subpial transection. No patients died among 199 with no seizure recurrence, whereas of 194 patients with seizure recurrence, 11 died. Six of the deaths were sudden and unexplained. Most patients who died had a substantial reduction in postoperative seizure frequency. The standardized mortality ratio for patients with recurrent seizures was 4.69, and the risk of death in these patients was 1.37 in 100 person-years, whereas among patients who became seizure free, there was no difference in mortality rate compared with the age- and sex-matched population of the United States. Elimination of seizures after surgery reduces mortality rates in people with epilepsy to a level indistinguishable from that of the general population, whereas patients with recurrent seizures continue to suffer from high mortality rates. This suggests that uncontrolled seizures are a major risk factor for excess mortality in epilepsy. Achieving complete seizure control with epilepsy surgery in refractory patients reduces the risk of death, so the long-term risk of continuing medical treatment appears to be higher than the risk of epilepsy surgery in suitable candidates.

Adolescent↗

A playroom observation procedure to assess children with mental retardation and ADHD.

Forty-two children (ages 6 to 12 years old) with moderate mental retardation to borderline intellectual functioning were studied in a laboratory playroom setting to determine whether children identified as ADHD (attention deficit hyperactivity disorder) or controls differed on activity and attentional measures. Children with ADHD were further divided into ADHD + conduct problems (ADHD + CD) and ADHD-only subgroups (with an ADHD-combined group comprising children of both subgroups). An interval recording system was used to code observations of independent play and a restricted academic task. Results indicated that the ADHD-combined group was significantly more vocal and engaged in a significantly greater number of toy changes than controls during independent play. Significant group differences were also noted during the restricted academic task, with the ADHD-combined and ADHD + CD groups more off-task and engaging in a greater number of toy touches than controls. Discriminant analyses found independent play measures to predict group membership in 70 percent of cases (ADHD-combined vs. controls), but in only 64 percent of cases using measures from the restricted academic task. No significant findings resulted when the ADHD subjects were further divided into two subgroups. Despite some inconsistent findings, such laboratory-based observations may be of value in the diagnosis of ADHD in children with moderate mental retardation to borderline intellectual functioning.

Attention Deficit Disorder with Hyperactivity↗

Predictors of overweight and overfatness in a multiethnic pediatric population. Child and Adolescent Trial for Cardiovascular Health Collaborative Research Group.

The goal of the study was to determine whether overweight or overfatness were predicted from sex, race or ethnicity, school site, and intervention or control status for children who were 9 y old at the outset of the Child and Adolescent Trial for Cardiovascular Health (CATCH). In this ethnically and geographically diverse group of 5106 students, height, weight, and triceps skinfold thickness were measured at 9 (baseline) and 11 y (follow-up) of age. The strongest predictors of status at follow-up were baseline overweight (odds ratio: 69.0; 95% CI: 54.9, 96.3) and overfatness (odds ratio: 27.4; 95% CI: 22.4, 33.4); site, African American race or ethnicity, and male sex were also significant independent associations. Children in the overweight (> 85th percentile for body mass index) group had significantly higher adjusted means for total blood cholesterol, higher apolipoprotein B concentrations, lower mean HDL-cholesterol concentrations, and lower performance on the 9-min run than those in other groups (< 15th, 15-49th, or 50-85th body mass index percentiles). Similar results were found for these factors for those subjects with greater triceps skinfold-thickness measurements. Groups of children who were overweight and overfat at baseline were more likely to be overweight and overfat at follow-up and to have more cardiovascular risk factors than their peers.

Apolipoproteins B↗

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.

Aged↗

Protein kinase C activity and protein levels in Alzheimer's disease.

Patients with Alzheimer's disease (AD) have been reported to have abnormalities in the levels and activities of protein kinase C (PKC) in brain and other tissues. We have measured Ca2+-activated, phospholipid-dependent PKC activities and levels in cerebral cortex from frontal, motor, temporal and parietal regions, as well as in leukocytes and platelets from AD patients and controls. No significant differences in PKC histone H1 phosphotransferase activity were seen in frontal, motor, temporal or parietal cortex, or in leukocytes and platelets from AD patients and controls. Elevated PKC protein was present in cytosolic fractions from frontal cortex, but not in other brain regions, or in leukocytes and platelets. These data suggest that abnormalities of PKC phosphorylating activity are absent in AD.

Aged↗

Physician characteristics: do they influence the evaluation and treatment of breast cancer in older women?

BACKGROUND: To determine if physician specialty, length of time in practice, and fear of malpractice influence the diagnosis and management of breast cancer in older women. METHODS: We used a fractional factorial design that controlled for patient age (65 or 80 years), race, socioeconomic status, mobility, comorbidity, and assertive behavior through 2 videotaped scenarios (a potential breast cancer [no. 1] and a known stage IIA breast cancer [no. 2]). One hundred twenty-eight white male physicians equally divided by specialty (surgeon versus nonsurgeon) and time in practice (< or = 15 or >15 years) viewed the videotapes and made recommendations. RESULTS: The physician subjects saw 46 patients per week, 59% female, and 47% age > or = 65. Their concern over malpractice was 4.7 (on a 10-point Likert scale with a higher score indicating more concern) and did not differ by specialty or time in practice (P values > 0.7). After viewing scenario no. 1, surgeons were less likely than nonsurgeons to consider breast cancer as the principal diagnosis (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2 to 0.9) and to obtain a tissue diagnosis (OR = 0.3, 95% CI = 0.1 to 0.9). However, in scenario no. 2, surgeons were more likely to offer reconstruction (OR = 3.8, 95% CI = 1.4 to 10.4). Physicians in practice < or = 15 years were more likely than those in practice <15 years to obtain a tissue diagnosis in scenario no. 1 (OR = 6.1, 95% CI = 1.9 to 19.2) and to perform full primary therapy in scenario no. 2 (OR = 2.8, 95% CI = 1.2 to 6.9). Physicians who performed an extensive metastatic evaluation (bone or computer tomography [CT] scan) had greater concern over malpractice than those who did not, as did physicians who performed an axillary node dissection (OR = 2.1, 95% CI 1.3 to 3.4 and OR = 1.8, 95% CI = 1.1 to 3.0). CONCLUSIONS: With the uncertainty of how to diagnose and treat older women with breast cancer, physician specialty, length of time in practice, and concern over malpractice do influence clinical decisions.

Age Factors↗

Regional HmPAO SPECT and CT measurements in the diagnosis of Alzheimer's disease.

BACKGROUND: This study investigated the hypothesis that the combination of regional CT brain atrophy measurements and semiquantitative SPECT regional blood flow ratios could produce a diagnostic test for Alzheimer's disease (AD) with an accuracy comparable to that achieved with the present clinical gold standard of the NINCDS-ADRDA criteria. METHODS: Single proton emission computed tomography (SPECT) and CT head scans were performed on 122 subjects referred an UBC Alzheimer clinic and diagnosed as either 'not demented' (ND-37) or 'possible/probable AD' (AD-85) by the NINCDS-ADRDA criteria. Stepwise discriminant analysis (SDA) was performed on the bilateral SPECT regions of interest and compared to bilateral CT qualitative/quantitative assessment in the frontal, parietal and temporal lobes to determine which were most accurate at ND/AD distinction. Receiver operating curves (ROC) were then constructed for these variables individually and for their combined discriminant function. RESULTS: The left temporal qualitative cortical atrophy score (CT) and left temporal perfusion ratio (SPECT) were selected in the SDA. The combined discriminant function was more specific at AD/ND distinction than either of CT or SPECT alone. The accuracy of AD/ND distinction with the combined discriminant function was below that achieved by clinical diagnosis according to the NINCDS-ADRDA criteria and was not significantly different from that achieved with SPECT or CT alone as defined by ROC curve analysis. CONCLUSION: The measurements of left temporal cortical atrophy and regional cerebral blood flow were most indicative of AD; however they lacked the sensitivity and specificity to recommend their use as a diagnostic test for AD.

Aged↗

A randomized, controlled trial of linopirdine in the treatment of Alzheimer's disease.

OBJECTIVES: We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease. METHODS: A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline. RESULTS: No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01. CONCLUSIONS: This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

Aged↗

Teaching pediatric residents about early intervention and special education.

We compared two educational interventions (didactic lecture with handouts vs guidelines placed in patient charts) and assessed their impact on knowledge of early developmental services and identification of children eligible for these services. Forty-nine pediatric residents participated in preintervention and postintervention tests of knowledge of such services. Mean scores for all residents were 54% (pre-test) and 60% (post-test). First-year residents scored significantly lower than 2nd- and 3rd-year residents on pre- (p = .0001) and post-tests (p < .02). From our convenience sample of 1204 patients, ages newborn to 6 years, seen in the resident continuity clinic during the study period, residents identified children eligible for early developmental services. The mean percentage of identifying eligible children was 13% (range, 0-40%). We did not detect a statistically significant impact of either educational strategy. We conclude, therefore, that more comprehensive strategies are needed to change physician knowledge of and behavior toward early developmental services.

Child, Preschool↗

SPECT in AD.

Explore the source record for details and available documents.

Alzheimer Disease↗

Clinical global measures of dementia. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines.

Following is the report of the committee working on clinical global measures for antidementia drug guidelines. The concepts involved in global scales, the distinctions between change and severity scales, advantages and disadvantages of structured interviews, and anchoring of change scores are discussed, and selected existing clinical global scales are described. In addition, the committee assessed the utility of global scales in clinical trials for antidementia drugs. There was a consensus among the members of the working group on the following: (1) Clinical global scales are interview based; in most cases, they include information obtained from caregivers as well as directly from patients, but they can rely on information from the subject only. (2) Clinicians' global ratings are intended to assess clinically meaningful change based on multidimensional clinical assessment and take into account the clinical heterogeneity of dementia by assessing at least cognition, behavior, and functioning. (3) There are two distinct types of clinical global measures: (a) clinicians' interview-based global severity scales, which generally incorporate classification by stage or severity of illness and (b) clinicians' interview-based global change scales, which incorporate global assessment ratings of clinical change. The committee could not reach a consensus on whether global scales should be required in phase II and phase III clinical trials, or whether other specific assessments such as well-designed activities of daily living, cognition, and behavior measures could, when used in appropriate combinations, replace the global as assessments of clinical meaningfulness.

Activities of Daily Living↗

Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study.

OBJECTIVE: To evaluate the risk of gastrointestinal and operative site bleeding associated with the use of parenteral ketorolac tromethamine. DESIGN: Postmarketing surveillance inception cohort study. SETTING: A total of 35 hospitals throughout the Philadelphia, Pa, region, 1991 to 1993. PATIENTS: Patients administered 10,272 courses of parenteral ketorolac therapy were compared with patients administered 10,247 courses of a parenteral opiate who were matched to the ketorolac patients by hospital, admitting service, and date of initiation of study drug. MAIN OUTCOME MEASURES: Medical records were reviewed for demographics, medical history, doses and duration of study drug, various aspects of the hospital course including surgery and concomitant medications, and adverse events. RESULTS: The multivariate adjusted odds ratio (OR) comparing ketorolac with opiates for gastrointestinal bleeding was 1.30 (95% confidence interval [CI], 1.11 to 1.52); for operative site bleeding, the OR was 1.02 (95% CI, 0.95 to 1.10). The OR was elevated further in subjects 75 years of age or older for both gastrointestinal bleeding (OR = 1.66; 95% CI, 1.23 to 2.25) and operative site bleeding (OR = 1.12; 95% CI, 0.94 to 1.35). A dose-response relationship was evident between average daily ketorolac dose and both gastrointestinal bleeding and operative site bleeding (trend test P < .001 for both). When analgesic therapy lasted 5 or fewer days, ketorolac was associated with only a small increased risk of gastrointestinal bleeding (OR = 1.17; 95% CI, 0.99 to 1.30); when therapy was prolonged beyond 5 days, the OR was 2.20 (95% CI, 1.36 to 3.57). The association of ketorolac with operative site bleeding was not affected by duration of therapy. CONCLUSIONS: The overall associations between ketorolac use and both gastrointestinal bleeding and operative site bleeding are small. However, the risk associated with the drug is larger and clinically important when ketorolac is used in higher doses, in older subjects, and for more than 5 days. Improving physicians' prescribing practices by limiting the dose and duration of ketorolac use, especially in the elderly, should enhance its overall risk-benefit balance.

Adolescent↗

Serum levels of the iron binding protein p97 are elevated in Alzheimer's disease.

Alzheimer's disease is a progressive and incurable disease whose prevalence increases dramatically with age. A biochemical marker for monitoring the onset and progression of the disease would be a valuable tool for disease management. In addition, such a marker might be used as an end point in clinical intervention protocols. Here we provide evidence that the soluble form of the iron binding protein p97 is found in elevated amounts in the serum of Alzheimer's patients compared with healthy controls. This biochemical marker has the potential for identifying subjects afflicted with the disease and possibly for monitoring the onset and longitudinal progression of the disease.

Adult↗