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H Feldman

Publications and source records attributed to H Feldman.

At least 19 recordsLinked to original sources
PubMed2001

A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease.

OBJECTIVE: To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores of 5 to 17; Functional Assessment Staging score < or =6 at baseline). METHODS: Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician's judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+). RESULTS: Patients' mean age was 73.6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean +/- SE sMMSE scores at baseline were 11.7 +/- 0.35 for the donepezil group and 12.0 +/- 0.34 for the placebo group. Patients receiving donepezil showed benefits on the CIBIC+, compared with placebo, at all visits up to week 24 (p < 0.001) and at week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary measures (including sMMSE, Severe Impairment Battery, Disability Assessment for Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) showed significant differences between the groups in favor of donepezil at week 24 LOCF. Eighty-four percent of donepezil- and 86% of placebo-treated patients completed the trial. Adverse events (AE) were experienced by 83% of donepezil- and 80% of placebo-treated patients, the majority of which were rated mild in severity; 8% of donepezil- and 6% of placebo-treated patients discontinued because of AE. Laboratory and vital sign abnormalities were similar between the treatment groups. CONCLUSION: These data suggest that donepezil's benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.

Activities of Daily Living↗
PubMed2001

Progression of impairment in patients with vascular cognitive impairment without dementia.

Little is known about progression, short of dementia, in vascular cognitive impairment. In the Canadian Study of Health and Aging, 149 participants (79.3 +/- 6.7 years; 61% women) were found to have vascular cognitive impairment, no dementia (CIND). After 5 years, 77 participants (52%) had died and 58 (46%) had developed dementia. Women were at greater risk of dementia (OR 2.1, 1.0 to 4.5). Of 32 participants alive without dementia, cognition had deteriorated in seven and improved in four. Half of those with vascular CIND developed dementia within 5 years, suggesting a target for preventive interventions.

Aged↗
PubMed2001

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

OBJECTIVE: i) To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians towards the recognition, assessment and management of dementing disorders; ii) 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 behaviour 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; 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 upon this evidence, consensus statements were developed by a group of experts, guided by a steering committee of eight 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, HARMS AND COSTS: Potential for improved clinical care of individuals with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. RECOMMENDATIONS: See text. VALIDATION: Four other sets of consensus statements and/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.

Aged↗
PubMed2001

Diagnosis, classification and natural history of degenerative dementias.

The release of the first approved medications for the treatment of Alzheimer's disease in Canada has highlighted the renewed need and importance of diagnostic accuracy and understanding of the spectrum of the dementias. The epidemiological scope of the problem of dementia in Canada including risk factors, caregiving patterns and costs of care have been well-characterized through the Canadian Study of Health and Aging (CSHA 1991-1996) with some of the key findings reviewed here. Beyond Alzheimer's disease the phenotypes and genotypes of the other degenerative dementias have been emerging with proposed operational diagnostic criteria that should facilitate their recognition in clinical practice. This paper reviews the clinical phenotypes of the most common causes of dementia with a proposed classification scheme and with discussion of their relevance from a differential treatment standpoint. This paper served as a background document for the working group of the Consensus Conference on Dementia (C3D) in February 1998 and has been revised subsequently for this publication.

Alzheimer Disease↗
PubMed2001

Effect of ethnicity on denial of authorization for emergency department care by managed care gatekeepers.

OBJECTIVE: After a pilot study suggested that African American patients enrolled in managed care organizations (MCOs) were more likely than whites to be denied authorization for emergency department (ED) care through gatekeeping, the authors sought to determine the association between ethnicity and denial of authorization in a second, larger study at another hospital. METHODS: A retrospective cohort design was used, with adjustment for triage score, age, gender, day and time of arrival at the ED, and type of MCO. RESULTS: African Americans were more likely to be denied authorization for ED visits by the gatekeepers representing their MCOs even after adjusting for confounders, with an odds ratio of 1.52 (95% CI = 1.18 to 1.94). CONCLUSIONS: African Americans were more likely than whites to be denied authorization for ED visits. The observational study design raises the possibility that incomplete control of confounding contributed to or accounted for the association between ethnicity and gatekeeping decisions. Nevertheless, the questions that these findings raise about equity of gatekeeping indicate a need for additional research in this area.

Adolescent↗
PubMed2000

Online measures of basic language skills in children with early focal brain lesions.

Twenty children with early focal lesions were compared with 150 age-matched control subjects on 11 online measures of the basic skills underlying language processing, a digit span task, and 6 standardized measures. Although most of the children with brain injury scored within the normal range on the majority of the tasks, they also had a disproportionately high number of outlier scores on the reaction time tests. This evidence for a moderate impairment of the basic skills underlying language processing contrasts with other evidence suggesting that these children acquire normal control of the functional use of language. Furthermore, these children scored within the normal range on a measure of general cognitive ability, suggesting that there is no particular sparing of linguistic functions at the expense of general cognitive functions. Using the MPD procedure (Valdés-Pérez & Pericliev, 1997), we found that the controls and the five clinical groups could be best distinguished with two measures of online processing (word repetition and visual number naming) and one standardized test subcomponent (the CELF Oral Directions subtest). The 12 children with left hemisphere lesions scored significantly lower than the 8 other children on the CELF-RS measure. Within the group of children with cerebral infarct, the nature of the processing disability could be linked fairly well to site of lesion. Otherwise, there was little relation between site or size of lesion and the pattern of deficit. These results support a model in which damage to the complex functional circuits subserving language leads to only minor deficits in process efficiency, because of the plasticity of developmental processes.

Brain Diseases↗
PubMed2000

Causes of Alzheimer's disease.

It is now understood that genetic factors play a crucial role in the risk of developing Alzheimer's disease (AD). Rare mutations in at least 3 genes are responsible for early-onset familial AD. A common polymorphism in the apolipoprotein E gene is the major determinant of risk in families with late-onset AD, as well as in the general population. Advanced age, however, remains the major established risk factor for AD, although environmental variables may also have some role in disease expression. Some pathogenic factors directly associated with aging include oxidative damage and mutations in messenger RNA. Other factors unrelated to the aging process may, in the future, be amenable to therapeutic intervention by way of estrogen replacement therapy for postmenopausal women, anti-inflammatory drug therapy and reducing vascular risk factors. Older theories, such as aluminum playing a role in the pathogenesis of AD, have been mostly discarded as our understanding of pathogenic mechanisms of AD has advanced.

Aged↗
PubMed2000

Age and sex differences in presentation of symptoms among patients with acute coronary disease: the REACT Trial. Rapid Early Action for Coronary Treatment.

BACKGROUND: There are few data on possible age and sex differences in presentation of symptoms for patients with acute coronary disease. OBJECTIVE: To investigate demographic differences in presentation of symptoms at the time of hospital presentation for acute myocardial infarction (AMI) and unstable angina. METHODS: The medical records of patients who presented with chest pain and who also had diagnoses of AMI (n = 889) or unstable angina (n = 893) on discharge from 43 hospitals were reviewed as part of data collection activities of the Rapid Early Action for Coronary Treatment trial based in 10 pair-matched communities throughout the USA. RESULTS: Dyspnea (49%), arm pain (46%), sweating (35%), and nausea (33%) were commonly reported by men and women of all ages in addition to the presenting complaint of chest pain. After we had controlled for various characteristics through regression modeling, older persons with AMI were significantly less likely than were younger persons to complain of arm pain and sweating, and men were significantly less likely to report vomiting than were women. Among persons with unstable angina, arm pain and sweating were reported significantly less often by elderly patients. Nausea and back, neck, and jaw pain were more common complaints of women. CONCLUSIONS: Results of this study suggest that there are differences between symptoms at presentation of men and women, and those in various age groups, hospitalized with acute coronary disease. Clinicians should be aware of these differences when diagnosing and managing patients suspected to have coronary heart disease.

Adult↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗