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Biomedical subjects

H Fillit

Publications and source records attributed to H Fillit.

At least 19 recordsLinked to original sources
PubMed2006

Apolipoprotein E-derived peptides reduce CNS inflammation: implications for therapy of neurological disease.

The apolipoprotein E4 isoform (apoE4) was initially identified as a susceptibility gene for the development of Alzheimer's disease, and has also recently been associated with poor outcome after acute traumatic and ischemic brain injury. One mechanism by which apoE may influence outcome in acute and chronic neurological disease is by downregulating glial activation and the neuroinflammatory response. Because it does not readily cross the blood-brain barrier (BBB), the apoE holoprotein has limited therapeutic potential. However, smaller peptides derived from the receptor binding region of apoE have been developed that mimic the functional anti-inflammatory and neuroprotective effects of the intact apoE protein. These apoE-derived therapeutic peptides cross the BBB and have been demonstrated to improve functional and histological outcomes in murine models of brain injury. Thus, the development of apoE-derived peptides represent a novel therapeutic strategy for the treatment of acute and chronic neurological disease.

Apolipoprotein E4↗
PubMed2002

Alzheimer's disease and related dementias increase costs of comorbidities in managed Medicare.

OBJECTIVES: To analyze the relationship between comorbid conditions and costs for patients with AD and related dementias (ADRD) in a Medicare managed care organization (MCO). To derive implications for improving management of patients with ADRD. METHODS: Retrospective analysis was carried out on administrative data for 3,934 patients with ADRD and 19,300 age/sex-matched control subjects enrolled in a large Medicare MCO. Patients with ADRD were identified from diagnoses on medical claims and encounter data for a 2-year period. Control subjects were selected from health plan members without dementia. Comorbid conditions were based on the diagnostic classifications from the Charlson comorbidity index. Health care costs and utilization for MCO-covered services for cases were compared with those of control subjects. RESULTS: Prevalence of ADRD was 4.4%, substantially higher than reported in previous studies of Medicare managed care and similar to population-based estimates. After controlling for comorbid conditions, age, and sex, annual costs were $4,134 higher for ADRD patients, resulting in excess costs of $16 million to the MCO. For the 10 most prevalent comorbidities in ADRD patients, adjusted costs were higher for ADRD patients compared with control subjects with the same condition. Higher costs were attributable to higher inpatient and skilled nursing facility utilization. CONCLUSIONS: In this study, prevalence rates for ADRD mirrored population estimates. Costs for patients with ADRD in this Medicare MCO varied considerably by comorbid condition and were substantially higher for patients with both AD and comorbid diseases commonly targeted for disease management, indicating that AD increases costs through effects on the management of comorbid illnesses. These findings indicate that better treatment and care management of AD could reduce the costs of comorbid illnesses commonly experienced by the frail elderly.

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PubMed2001

The effect of a fitness program on health status and health care consumption in Medicare MCOs.

This study examined the effect of a fitness program for Medicare MCOs on health status and health care utilization of participants. An evaluation compared outcome measures between high-level and low-level participants of the program. High-level participants scored higher on the Health Outcomes Survey and also had fewer doctor visits during the program period compared with low-level participants. The authors conclude that elderly individuals who participated at the high-level rate in a targeted fitness program maintained or improved health status and had fewer outpatient visits compared with the low-level participants. Medicare MCOs may improve health and manage costs for members by employing similar interventions focusing on functional health through exercise.

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PubMed2000

Practice guidelines for the diagnosis and treatment of Alzheimer's disease in a managed care setting: Part II--Pharmacologic therapy. Alzheimer's Disease (AD) Managed Care Advisory Council.

The progressive loss of social and physical functioning associated with Alzheimer's disease (AD) results in extensive social and economic costs to society. The early diagnosis and treatment of AD may reduce cognitive and behavioral symptoms of this disease and may slow disease progression, thereby alleviating some of these social and economic costs. The Alzheimer's Disease Managed Care Advisory Council, a panel of experts from managed care, academic medicine, and the Los Angeles chapter of the Alzheimer's Association was convened to synthesize current evidence-based recommendations for AD diagnostic and treatment guidelines and to integrate these guidelines for use in MCOs. This paper presents conclusions from this panel and provides an algorithm for the treatment of AD specifically for managed care settings. When combined with other necessary efforts to educate providers, these guidelines should improve the cost-effectiveness and quality of care for individuals with dementia in managed care.

Algorithms↗
PubMed1999

Donepezil use in managed Medicare: effect on health care costs and utilization.

Donepezil is one of the first effective and well-tolerated medications approved for the treatment of Alzheimer's disease (AD). This study examined the impact of donepezil on the costs of AD in a multisite managed care organization between January 1, 1996, and March 31, 1998. A pretreatment/posttreatment study was conducted using retrospective medical and prescription claims data for 70 individuals with AD and related dementias who were prescribed donepezil. The outcomes of interest were costs during the pretreatment and posttreatment phases, which were categorized as medical, prescription, and combined costs. Per diem costs were adjusted for differences in the duration of follow-up. We found that median per diem medical costs were $1.22 lower in the posttreatment phase than in the pretreatment phase (P = 0.02). Moreover, posttreatment costs were reduced in 6 of 7 service settings, with median per diem savings of $0.77 in outpatient care (P = 0.002) and $0.65 in office visits (P < 0.001). In the posttreatment phase, the median per diem costs for prescriptions and all claims combined were higher by $2.59 (P < 0.001) and $2.11 (P = 0.04), respectively. Donepezil treatment was associated with a decrease in medical costs, particularly in the outpatient components of health care. However, overall costs were increased due to the higher costs of medication. Further pharmacoeconomic studies are needed to determine the exact impact of acetylcholinesterase-inhibitor therapy on the overall costs of care for individuals with dementia.

Aged↗
PubMed1999

Regulation of the heparan sulfate proteoglycan, perlecan, by injury and interleukin-1alpha.

Perlecan is a specific proteoglycan that binds to amyloid precursor protein and beta-amyloid peptide, is present within amyloid deposits, and has been implicated in plaque formation. Because plaque formation is associated with local inflammation, we hypothesized that the mechanisms involved in brain inflammatory responses could influence perlecan biosynthesis. To test this hypothesis, we first studied perlecan regulation in mice after inflammation induced by a brain stab wound. Perlecan mRNA and immunoreactivity were both increased 3 days after injury. Interleukin-1alpha (IL-1alpha) is a cytokine induced after injury and plays an important role in inflammation. As such, IL-1alpha may be one of the factors participating in regulating perlecan synthesis. We thus studied perlecan regulation by IL-1alpha, in vivo. Regulation of perlecan mRNA by this cytokine was area-specific, showing up-regulation in hippocampus, whereas in striatum, perlecan mRNA was unchanged. To support this differential regulation of perlecan mRNA by IL-1alpha, basic fibroblast growth factor (bFGF), a growth factor also present in plaques, was studied in parallel. bFGF mRNA did not show any regional difference, being up-regulated in both hippocampus and striatum in vivo. In vitro, both astrocyte and microglia were immunoreactive for perlecan. Moreover, perlecan mRNA was increased in hippocampal glial cultures after IL-1alpha but not in striatal glia. These results show an increase in perlecan biosynthesis after injury and suggest a specific regulation of perlecan mRNA by IL-1alpha, which depends on brain area. Such regulation may have important implications in the understanding of regional brain variations in amyloid plaque formation.

Alzheimer Disease↗
PubMed1999

Cost of Alzheimer's disease and related dementia in managed-medicare.

BACKGROUND: Managed care organizations (MCOs) will have increased responsibility for the care of large numbers of persons with dementia. There are, however, few studies that inform about decisions of healthcare utilization and expenditures for individuals with dementia in managed care. OBJECTIVES: To examine in a large MCO whether people diagnosed with dementia have higher healthcare utilization and costs than enrollees without dementia. DESIGN: A retrospective study of medical and prescription claims. SETTING: An MCO covering more than 80,000 Medicare enrollees in four geographical locales between January 1, 1996, and March 31, 1998. SUBJECTS: There were 677 paired cases with and without dementia. Controls were selected randomly and matched to cases on age, gender, and region. MEASUREMENTS: Summed total costs and number of claims accrued during the study period, as well as a breakdown of costs and claims with respect to place of service, were annualized and adjusted for age, gender, and comorbid conditions. Costs and claims were broken down by place of service. RESULTS: Dementia prevalence was 0.83%. Mean total costs were 1.5 times higher for patients with dementia relative to controls ($13,487 vs $9,276, P < .001) when annualized and adjusted for level of comorbidity. Almost 75% of the higher costs among cases were linked to inpatient expenses. CONCLUSIONS: Higher costs for individuals with dementia and disproportionate inpatient costs in this MCO parallel patterns among Medicare enrollees in fee-for-service. The high prevalence of dementia among the oldest old coupled with the high costs of dementia care create very significant clinical and financial incentives for managed care plans to improve the care of members suffering from dementia.

Age Distribution↗
PubMed1999

Opportunities for improving managed care for individuals with dementia: Part 1--The issues.

In this first part of a two-part article, we review the prevalence of, costs associated with, and treatments for Alzheimer's disease and related dementias, a leading cause of disability in the elderly. New, innovative, and costly drugs to combat dementia are being introduced, causing pharmacy costs to rise. These new drugs, however, may reduce overall medical costs and improve the quality of life of patients with dementia and their caregivers. Issues of cost, excessive service utilization, and quality of life will have significant impact on managed care organizations in the near future as the rapidly aging population experiences significant disability and illness related to dementia. In the second part of this article, we describe the framework for a disease management program for patients with dementia, similar to programs in existence for diabetes and other chronic diseases, that could enable managed care organizations to effectively care for these patients.

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PubMed1999

Opportunities for improving managed care for individuals with dementia: Part 2--A framework for care.

In this second part of a review of dementia, we argue that managed care organizations must develop strategies to identify and manage patients with dementia, whose numbers will increase dramatically in the near future. Improved coding and use of validated self-report instruments that include caregivers as information sources could assist in identifying patients with dementia who could benefit from disease management programs. These programs should include population-based screening efforts; the development of practice guidelines; the use of case managers; education of caregivers, case managers, and physicians in issues such as availability of community services, patient/caregiver self-management techniques, and the latest developments in efficacious treatment; and monitoring of care through quality assurance activities. Dementia is a highly prevalent, devastating, and costly chronic illness of the elderly, but it is also eminently manageable. Managed care has the potential to improve the quality of life and care for these patients, while managing the costs.

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PubMed1998

Heparin oligosaccharides that pass the blood-brain barrier inhibit beta-amyloid precursor protein secretion and heparin binding to beta-amyloid peptide.

We have previously demonstrated that full-length heparin stimulates the synthesis and secretion of beta-amyloid precursor protein (APP) through an amyloidogenic pathway in neuroblastoma cells. In the present study, heparin was chemically depolymerized, and the effect of low-molecular-weight (LMW) heparin on APP secretion was investigated. In contrast to full-length heparin, LMW heparin had no significant effect on APP secretion. However, LMW heparin fragments, especially heparin disaccharides, were able to inhibit efficiently the stimulatory effect of heparin on APP secretion. LMW heparin derivatives also inhibit the binding of heparin to the beta-amyloid peptide (1-28). Using an in vitro model, we further demonstrated the passage of LMW heparin derivatives through the blood-brain barrier. This study suggests that LMW heparin derivatives or analogues may be effective as therapeutic agents to prevent or slow the process of amyloidogenesis in Alzheimer's disease.

Amyloid beta-Protein Precursor↗
PubMed1997

Use of ineffective or unsafe medications among members of a Medicare HMO compared to individuals in a Medicare fee-for-service program.

Adverse drug reactions and inappropriate prescribing practices are an important cause of hospitalization, morbidity, and mortality in the elderly. This study compares prescribing practices within a Medicare risk contract health maintenance organization (HMO) in 1993 and 1994 with prescribing practices for two nationally representative samples of elderly individuals predominantly receiving medical care within the Medicare fee-for-service sector. Information on prescriptions in the fee-for-service sector came from the 1987 National Medical Expenditures Survey (NMES) and the 1992 Medicare Current Beneficiary Survey (MCBS). A total of 20 drugs were studied; these drugs were deemed inappropriate for the elderly because their risk of causing adverse events exceeded their health benefits, according to a consensus panel of experts in geriatrics and pharmacology. One or more of the 20 potentially inappropriate drugs was prescribed to 11.53% of the Medicare HMO members in 1994. These medications were prescribed significantly less often to HMO members in 1994 than to individuals in the fee-for-service sector, based on information from both the 1987 NMES and the 1992 MCBS. Utilization of unsafe or ineffective medications actually decreased with increasing age in the HMO sample, with lowest rates in individuals over the age of 85. However, no relationship between age and medication use was seen in the NMES study, except for individuals over the age of 90 years. The study data support the conclusion that ineffective or unsafe medications were prescribed less often in the Medicare HMO than in national comparison groups. In fact, for the very old, who are most at risk, the use of these medications was much lower in the Medicare HMO than in the Medicare fee-for-service sector. Nevertheless, in 1994, approximately one of every nine members of this Medicare HMO received at least one such medication. Continued efforts and innovative strategies to further reduce the use of unsafe and ineffective drugs among elderly Medicare HMO members are needed.

Aged↗
PubMed1996

Autoimmune MRL mice express high-affinity IgG2b monoclonal autoantibodies to heparin.

Heparin and heparan sulfate are related glycosaminoglycans which demonstrate high-affinity interactions with a number of proteins, including antithrombin III. The immunogenicity of heparin has been reported previously employing heparin-protein conjugates as immunogens and as antigens in solid-phase assays. Previous studies also demonstrate that anti-heparin antibodies play a role in autoimmune diseases including systemic lupus and anti-phospholipid syndrome and in patients who receive heparin for therapeutic purposes. In the current study, we investigated the expression of monoclonal anti-heparin antibodies in nonimmunized, autoimmune MRL/lpr/lpr++ mice employing a liquid-phase radioimmunoassay. The Kd of monoclonal IgG2b autoantibodies for heparin was approximately 10(-8)M. Anti-heparin antibodies were precipitating, and were not polyreactive. The IgG monoclonal antibodies described in this study represent an immunological instance of a specific, high-affinity heparin-protein interaction.

Animals↗
PubMed1995

Future therapeutic developments of estrogen use.

The potential long-term benefits of estrogen replacement therapy (ERT) in the prevention of osteoporosis and heart disease have been reasonably well established. However, the favorable effects of ERT on cognitive function and prevention of senile dementia in old age now represents a revitalized area of clinical research. A growing body of experimental evidence has recently provided the neurobiologic basis to support the hypothesis that gonadal hormones such as estrogen have psychologic effects on human brain function and behavior. Studies in women who have undergone surgical menopause have demonstrated that the menopause is associated with subclinical cognitive and affective dysfunction, which is improved by ERT. In addition, a growing body of evidence suggests that estrogen may be an effective therapy for senile dementia in some elderly women. Recent epidemiologic studies have indicated that long-term postmenopausal ERT may prevent late-life cognitive dysfunction in older women. Several clinical trials employing oral estrogen therapy have also observed that some aged women with senile dementia have improved cognitive and affective function after estrogen therapy. Estrogen loss resulting in cognitive disorders, including menopausal cognitive dysfunction and senile dementia in late life, may act via several mechanisms. Estrogen may be an important growth factor for estrogen-responsive neurons. Estrogen therapy may also have substantial neurochemical effects, direct effects on the vasculature, and effects on the generation of free radicals, which may be toxic to neurons. At this time, several important clinical questions need to be answered regarding the role of ERT in the cognitive and affective dysfunctions associated with menopause and senile dementia. Should estrogen be used for menopausal women whose sole complaint is cognitive or affective dysfunction? Does long-term ERT prevent cognitive decline in late life if initiated at the time of menopause? Can ERT improve cognition and affective function in postmenopausal women with Alzheimer's disease, and does estrogen therapy prevent the progression of Alzheimer's disease in these patients? Finally, do the vascular effects of estrogen play a role in the treatment or prevention of both Alzheimer's disease and vascular dementia?

Aged↗
PubMed1995

Cytotoxicity to endothelial cells by sera from aged MRL/lpr/lpr mice is associated with autoimmunity to cell surface heparan sulfate.

Vasculitis is an common clinical feature of systemic lupus erythematosus (SLE) in humans and in animal models of this disease. Humoral autoimmunity against endothelial cells has been previously demonstrated in SLE and other autoimmune disorders, but the precise cell surface antigenic targets involved in the initiation and progression of vascular injury are still essentially unknown. In the current studies, we demonstrate the presence of autoantibodies in the sera of MRL/lpr/lpr mice which bind endothelial cell surface antigens by ELISA and also cause complement-dependent cytotoxicity of these cells. These MRL/lpr/lpr sera induced complement-dependent cleavage and release of 35SO4-labeled material containing primarily cell surface heparan sulfate proteoglycans from these cells, and react with heparin (a glycosaminoglycan related to heparan sulfate) by ELISA and liquid-phase competitive inhibition ELISA. These data indicate that antiendothelial cell autoantibodies present in autoimmune MRL/lpr/lpr mice are directed at least in part against cell surface heparan sulfate proteoglycans. Autoantibodies to cell surface heparan sulfate proteoglycan may play a role in vascular endothelial cell injury in these animals through complement-dependent, autoimmune mechanisms.

Animals↗
PubMed1995

House calls: a practical guide to seeing the patient at home.

The physician and/or healthcare team is responsible for the planning, design, implementation, and authorization of home care services. Home visits are appropriate for elderly homebound patients and for those who are having problems at home, such as recent falls or suspected abuse. The home visit can provide valuable information that is not readily accessible in the office setting. At the home, the comprehensive geriatric assessment should include history and physical exam, plus a medication review, environmental evaluation, and assessment of functional status. Discussion with the family is also important, as caregiver burnout can adversely affect the well-being of the frail older patient living at home. Environmental modifications can improve home safety and reduce the risk for falls.

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