Showing papers by "Veterans Health Administration published in 2000"

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

Abstract: Background: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. Objective: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. Design: Prospective, observational study. Setting: HIV clinics in a Veterans Affairs medical center and a university medical center. Patients: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). Measurements: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). Results: During the study period, 45 397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P 5 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P 5 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P 5 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. Conclusions: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Factors Considered Important at the End of Life by Patients, Family, Physicians, and Other Care Providers

Abstract: ContextA clear understanding of what patients, families, and health care practitioners view as important at the end of life is integral to the success of improving care of dying patients. Empirical evidence defining such factors, however, is lacking.ObjectiveTo determine the factors considered important at the end of life by patients, their families, physicians, and other care providers.Design and SettingCross-sectional, stratified random national survey conducted in March-August 1999.ParticipantsSeriously ill patients (n = 340), recently bereaved family (n = 332), physicians (n = 361), and other care providers (nurses, social workers, chaplains, and hospice volunteers; n = 429).Main Outcome MeasuresImportance of 44 attributes of quality at the end of life (5-point scale) and rankings of 9 major attributes, compared in the 4 groups.ResultsTwenty-six items consistently were rated as being important (>70% responding that item is important) across all 4 groups, including pain and symptom management, preparation for death, achieving a sense of completion, decisions about treatment preferences, and being treated as a "whole person." Eight items received strong importance ratings from patients but less from physicians (P<.001), including being mentally aware, having funeral arrangements planned, not being a burden, helping others, and coming to peace with God. Ten items had broad variation within as well as among the 4 groups, including decisions about life-sustaining treatments, dying at home, and talking about the meaning of death. Participants ranked freedom from pain most important and dying at home least important among 9 major attributes.ConclusionsAlthough pain and symptom management, communication with one's physician, preparation for death, and the opportunity to achieve a sense of completion are important to most, other factors important to quality at the end of life differ by role and by individual. Efforts to evaluate and improve patients' and families' experiences at the end of life must account for diverse perceptions of quality.

Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway

Abstract: The stress-inducible protein heme oxygenase-1 provides protection against oxidative stress. The anti-inflammatory properties of heme oxygenase-1 may serve as a basis for this cytoprotection. We demonstrate here that carbon monoxide, a by-product of heme catabolism by heme oxygenase, mediates potent anti-inflammatory effects. Both in vivo and in vitro, carbon monoxide at low concentrations differentially and selectively inhibited the expression of lipopolysaccharide-induced pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-1β and increased the lipopolysaccharide-induced expression of the anti-inflammatory cytokine interleukin-10. Carbon monoxide mediated these anti-inflammatory effects not through a guanylyl cyclase–cGMP or nitric oxide pathway, but instead through a pathway involving the mitogen-activated protein kinases. These data indicate the possibility that carbon monoxide may have an important protective function in inflammatory disease states and thus has potential therapeutic uses.

Use of Colonoscopy to Screen Asymptomatic Adults for Colorectal Cancer

Abstract: Background and Methods The role of colonoscopy in screening for colorectal cancer is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine the prevalence and location of advanced colonic neoplasms and the risk of advanced proximal neoplasia in asymptomatic patients (age range, 50 to 75 years) with or without distal neoplasia. Advanced colonic neoplasia was defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. In patients with more than one neoplastic lesion, classification was based on the most advanced lesion. Results Of 17,732 patients screened for enrollment, 3196 were enrolled; 3121 of the enrolled patients (97.7 percent) underwent complete examination of the colon. The mean age of the patients was 62.9 years, and 96.8 percent were men. Colonoscopic examination showed one or more neoplastic lesions in 37.5 percent of the patients, an adenoma with a diameter of at least 10 mm or a villous...

Role of CD47 as a marker of self on red blood cells.

Abstract: The immune system recognizes invaders as foreign because they express determinants that are absent on host cells or because they lack "markers of self" that are normally present. Here we show that CD47 (integrin-associated protein) functions as a marker of self on murine red blood cells. Red blood cells that lacked CD47 were rapidly cleared from the bloodstream by splenic red pulp macrophages. CD47 on normal red blood cells prevented this elimination by binding to the inhibitory receptor signal regulatory protein alpha (SIRPalpha). Thus, macrophages may use a number of nonspecific activating receptors and rely on the presence or absence of CD47 to distinguish self from foreign. CD47-SIRPalpha may represent a potential pathway for the control of hemolytic anemia.

The effect of fecal occult-blood screening on the incidence of colorectal cancer.

Abstract: Background Both annual testing for fecal occult blood and biennial testing significantly reduce mortality from colorectal cancer. However, the effect of screening on the incidence of colorectal cancer remains uncertain, despite the diagnosis and removal of precancerous lesions in many persons who undergo screening. Methods We have followed the participants in the Minnesota Colon Cancer Control Study for 18 years. A total of 46,551 people, most of whom were 50 to 80 years old, were enrolled between 1975 and 1978 and randomly assigned to annual screening, biennial screening, or usual care (the control group). Those assigned to the screening groups were asked to prepare and submit two samples from each of three consecutive stools for guaiac-based testing. Those with at least one positive slide in the set of six were offered a diagnostic examination that included colonoscopy. Screening was conducted between 1976 and 1982 and again between 1986 and 1992. Study participants have been followed with respect to ne...

Zygomycetes in Human Disease

Abstract: The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk factors. The Entomophthorales are closely related to the Mucorales on the basis of sexual growth by production of zygospores and by the production of coenocytic hyphae. Despite these similarities, the Entomophthorales and Mucorales have dramatically different gross morphologies, asexual reproductive characteristics, and disease manifestations. In comparison to the floccose aerial mycelium of the Mucorales, the Entomophthorales produce a compact, glabrous mycelium. The asexually produced spores of the Entomophthorales may be passively released or actively expelled into the environment. Human disease with these organisms occurs predominantly in tropical regions, with transmission occurring by implantation of spores via minor trauma such as insect bites or by inhalation of spores into the sinuses. Conidiobolus typically infects mucocutaneous sites to produce sinusitis disease, while Basidiobolus infections occur as subcutaneous mycosis of the trunk and extremities. The Entomophthorales are true pathogens, infecting primarily immunocompetent hosts. They generally do not invade blood vessels and rarely disseminate. Occasional cases of disseminated and angioinvasive disease have recently been described, primarily in immunocompromised patients, suggesting a possible emerging role for this organism as an opportunist.

Effects of Controlled-Release Metoprolol on Total Mortality, Hospitalizations, and Well-being in Patients With Heart Failure: The Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)

Abstract: For editorial comment see p 1335. Context Results from recent studies on the effects of b1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of b1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. Objective To examine the effects of the b1-blocker controlled-release/extendedrelease metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure.

In search of a good death: observations of patients, families, and providers.

Abstract: Despite a recent increase in the attention given to improving end-of-life care, our understanding of what constitutes a good death is surprisingly lacking. The purpose of this study was to gather descriptions of the components of a good death from patients, families, and providers through focus group discussions and in-depth interviews. Seventy-five participants-including physicians, nurses, social workers, chaplains, hospice volunteers, patients, and recently bereaved family members-were recruited from a university medical center, a Veterans Affairs medical center, and a community hospice. Participants identified six major components of a good death: pain and symptom management, clear decision making, preparation for death, completion, contributing to others, and affirmation of the whole person. The six themes are process-oriented attributes of a good death, and each has biomedical, psychological, social, and spiritual components. Physicians' discussions of a good death differed greatly from those of other groups. Physicians offered the most biomedical perspective, and patients, families, and other health care professionals defined a broad range of attributes integral to the quality of dying. Although there is no "right" way to die, these six themes may be used as a framework for understanding what participants tend to value at the end of life. Biomedical care is critical, but it is only a point of departure toward total end-of-life care. For patients and families, psychosocial and spiritual issues are as important as physiologic concerns.

Impact of disseminating quality improvement programs for depression in managed primary care: A randomized controlled trial.

Abstract: ContextCare of patients with depression in managed primary care settings often fails to meet guideline standards, but the long-term impact of quality improvement (QI) programs for depression care in such settings is unknown.ObjectiveTo determine if QI programs in managed care practices for depressed primary care patients improve quality of care, health outcomes, and employment.DesignRandomized controlled trial initiated from June 1996 to March 1997.SettingForty-six primary care clinics in 6 US managed care organizations.ParticipantsOf 27,332 consecutively screened patients, 1356 with current depressive symptoms and either 12-month, lifetime, or no depressive disorder were enrolled.InterventionsMatched clinics were randomized to usual care (mailing of practice guidelines) or to 1 of 2 QI programs that involved institutional commitment to QI, training local experts and nurse specialists to provide clinician and patient education, identification of a pool of potentially depressed patients, and either nurses for medication follow-up or access to trained psychotherapists.Main Outcome MeasuresProcess of care (use of antidepressant medication, mental health specialty counseling visits, medical visits for mental health problems, any medical visits), health outcomes (probable depression and health-related quality of life [HRQOL]), and employment at baseline and at 6- and 12-month follow-up.ResultsPatients in QI (n = 913) and control (n = 443) clinics did not differ significantly at baseline in service use, HRQOL, or employment after nonresponse weighting. At 6 months, 50.9% of QI patients and 39.7% of controls had counseling or used antidepressant medication at an appropriate dosage (P<.001), with a similar pattern at 12 months (59.2% vs 50.1%; P = .006). There were no differences in probability of having any medical visit at any point (each P≥.21). At 6 months, 47.5% of QI patients and 36.6% of controls had a medical visit for mental health problems (P = .001), and QI patients were more likely to see a mental health specialist at 6 months (39.8% vs 27.2%; P<.001) and at 12 months (29.1% vs 22.7%; P = .03). At 6 months, 39.9% of QI patients and 49.9% of controls still met criteria for probable depressive disorder (P = .001), with a similar pattern at 12 months (41.6% vs 51.2%; P = .005). Initially employed QI patients were more likely to be working at 12 months relative to controls (P = .05).ConclusionsWhen these managed primary care practices implemented QI programs that improve opportunities for depression treatment without mandating it, quality of care, mental health outcomes, and retention of employment of depressed patients improved over a year, while medical visits did not increase overall.

Functional and clinical significance of skeletal muscle architecture.

Abstract: Skeletal muscle architecture is the structural property of whole muscles that dominates their function. This review describes the basic architectural properties of human upper and lower extremity muscles. The designs of various muscle groups in humans and other species are analyzed from the point of view of optimizing function. Muscle fiber arrangement and motor unit arrangement is discussed in terms of the control of movement. Finally, the ability of muscles to change their architecture in response to immobilization, eccentric exercise, and surgical tendon transfer is reviewed. Future integrative physiological studies will provide insights into the mechanisms by which such adaptations occur. It is likely that muscle fibers transduce both stress and strain and respond by modifying sarcomere number in a way more suited to the new biomechanical environment.

Criteria for cure of acromegaly: a consensus statement.

Abstract: In February 1999, a workshop was held in Cortina, Italy to develop a consensus defining the criteria for cure of acromegaly. The workshop was sponsored by the University of Brescia and hosted by the Italian Society of Endocrinology. Invited international participants included endocrinologists, neurosurgeons, and radiotherapists skilled in the management of acromegaly. This statement summarizes the consensus achieved in these discussions.

Fracture Risk Reduction with Alendronate in Women with Osteoporosis: The Fracture Intervention Trial

Abstract: We examined the effect of alendronate treatment for 3-4 yr on risk of new fracture among 3658 women with osteoporosis enrolled in the Fracture Intervention Trial. This cohort included women with existing vertebral fracture and those with osteoporosis as defined by T score of less than -2.5 at the femoral neck but without vertebral fracture. All analyses were prespecified in the data analysis plan. The magnitudes of reduction of fracture incidence with alendronate were similar in both groups. The two groups were, therefore, pooled to obtain a more precise estimate of the effect of alendronate on relative risk of fracture (relative risk, 95% confidence interval): hip (0.47, 0.26-0.79), radiographic vertebral (0.52, 0.42-0.66), clinical vertebral (0.55, 0.36-0.82), and all clinical fractures (0.70, 0.59-0.82). Reductions in risk of clinical fracture were statistically significant by 12 months into the trial. We conclude that reductions in fracture risk during treatment with alendronate are consistent in women with existing vertebral fractures and those without such fractures but with bone mineral density in the osteoporotic range. Furthermore, reduction in risk is evident early in the course of treatment. This pooled analysis provides a more precise estimate of the antifracture efficacy of alendronate in women with osteoporosis than that in prior reports.

Ibuprofen Suppresses Plaque Pathology and Inflammation in a Mouse Model for Alzheimer's Disease

Abstract: The brain in Alzheimer9s disease (AD) shows a chronic inflammatory response characterized by activated glial cells and increased expression of cytokines and complement factors surrounding amyloid deposits. Several epidemiological studies have demonstrated a reduced risk for AD in patients using nonsteroidal anti-inflammatory drugs (NSAIDs), prompting further inquiries about how NSAIDs might influence the development of AD pathology and inflammation in the CNS. We tested the impact of chronic orally administered ibuprofen, the most commonly used NSAID, in a transgenic model of AD displaying widespread microglial activation, age-related amyloid deposits, and dystrophic neurites. These mice were created by overexpressing a variant of the amyloid precursor protein found in familial AD. Transgene-positive (Tg+) and negative (Tg−) mice began receiving chow containing 375 ppm ibuprofen at 10 months of age, when amyloid plaques first appear, and were fed continuously for 6 months. This treatment produced significant reductions in final interleukin-1β and glial fibrillary acidic protein levels, as well as a significant diminution in the ultimate number and total area of β-amyloid deposits. Reductions in amyloid deposition were supported by ELISA measurements showing significantly decreased SDS-insoluble Aβ. Ibuprofen also decreased the numbers of ubiquitin-labeled dystrophic neurites and the percentage area per plaque of anti-phosphotyrosine-labeled microglia. Thus, the anti-inflammatory drug ibuprofen, which has been associated with reduced AD risk in human epidemiological studies, can significantly delay some forms of AD pathology, including amyloid deposition, when administered early in the disease course of a transgenic mouse model of AD.

Lack of Effect of a Low-Fat, High-Fiber Diet on the Recurrence of Colorectal Adenomas

Abstract: Background We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. Methods We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. Results A total of 1905 of the randomized subjects (91....

Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men

Abstract: Testosterone (T) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency, including improvement of sexual function, increase in muscle mass and strength, and decrease in fat mass, with minimal adverse effects. We have shown that administration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to the normal adult male range. We now report the effects of 180 days of treatment with this 1% T gel preparation (50 or 100 mg/day, contained in 5 or 10 g gel, respectively) compared to those of a permeation-enhanced T patch (5 mg/day) on defined efficacy parameters in 227 hypogonadal men. In the T gel groups, the T dose was adjusted up or down to 75 mg/day (contained in 7.5 g gel) on day 90 if serum T concentrations were below or above the normal male range. No dose adjustment was made with the T patch group. Sexual function and mood changes were monitored by questionnaire, body composition was determined by dual energy x-ray absorptiometry, and muscle strength was measured by the one repetitive maximum technique on bench and leg press exercises. Sexual function and mood improved maximally on day 30 of treatment, without differences across groups, and showed no further improvement with continuation of treatment. Mean muscle strength in the leg press exercise increased by 11 to 13 kg in all treatment groups by 90 days and did not improve further at 180 days of treatment. Moderate increases were also observed in arm/chest muscle strength. At 90 days of treatment, lean body mass increased more in the 100 mg/day T gel group (2.74 6 0.28 kg; P 5 0.0002) than in the 50 mg/day T gel (1.28 6 0.32 kg) and T patch groups (1.20 6 0.26 kg). Fat mass and percent fat were not significantly decreased in the T patch group, but showed decreases in the T gel groups (50 mg/day, 20.90 6 0.32 kg; 100 mg/day, 21.05 6 0.22 kg). The increase in lean mass and the decrease in fat mass were correlated with the changes in average serum T levels attained after transdermal T replacement. These beneficial effects of T replacement were accompanied by the anticipated increases in hematocrit and hemoglobin but without significant changes in the lipid profile. The increase in mean serum prostate-specific antigen levels (within the normal range) was correlated with serum levels of T. The greatest increases were noted in the 100 mg/day T gel group. Skin irritation was reported in 5.5% of subjects treated with T gel and in 66% of subjects in the permeationenhanced T patch group. We conclude that T gel replacement improved sexual function and mood, increased lean mass and muscle strength (principally in the legs), and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch. (J Clin Endocrinol Metab 85: 2839 ‐2853, 2000)

The public release of performance data: what do we expect to gain? A review of the evidence.

Abstract: ContextInformation about the performance of hospitals, health professionals, and health care organizations has been made public in the United States for more than a decade. The expected gains of public disclosure have not been made clear, and both the benefits and potential risks have received minimal empirical investigation.ObjectiveTo summarize the empirical evidence concerning public disclosure of performance data, relate the results to the potential gains, and identify areas requiring further research.Data SourcesA literature search was conducted on MEDLINE and EMBASE databases for articles published between January 1986 and October 1999 in peer-reviewed journals. Review of citations, public documents, and expert advice was conducted to identify studies not found in the electronic databases.Study SelectionDescriptive, observational, or experimental evaluations of US reporting systems were selected for inclusion.Data ExtractionIncluded studies were organized based on use of public data by consumers, purchasers, physicians, and hospitals; impact on quality of care outcomes; and costs.Data SynthesisSeven US reporting systems have been the subject of published empirical evaluations. Descriptive and observational methods predominate. Consumers and purchasers rarely search out the information and do not understand or trust it; it has a small, although increasing, impact on their decision making. Physicians are skeptical about such data and only a small proportion makes use of it. Hospitals appear to be most responsive to the data. In a limited number of studies, the publication of performance data has been associated with an improvement in health outcomes.ConclusionsThere are several potential gains from the public disclosure of performance data, but use of the information by provider organizations for quality improvement may be the most productive area for further research.

Protein kinase C isozymes and the regulation of diverse cell responses

Abstract: Individual protein kinase C (PKC) isozymes have been implicated in many cellular responses important in lung health and disease, including permeability, contraction, migration, hypertrophy, proliferation, apoptosis, and secretion. New ideas on mechanisms that regulate PKC activity, including the identification of a novel PKC kinase, 3-phosphoinositide-dependent kinase-1 (PDK-1), that regulates phosphorylation of PKC, have been advanced. The importance of targeted translocation of PKC and isozyme-specific binding proteins (like receptors for activated C-kinase and caveolins) is well established. Phosphorylation state and localization are now thought to be key determinants of isozyme activity and specificity. New concepts on the role of individual PKC isozymes in proliferation and apoptosis are emerging. Opposing roles for selected isozymes in the same cell system have been defined. Coupling to the Wnt signaling pathway has been described. Phenotypes for PKC knockout mice have recently been reported. More specific approaches for studying PKC isozymes and their role in cell responses have been developed. Strengths and weaknesses of different experimental strategies are reviewed. Future directions for investigation are identified.

Impaired Recognition Memory in Rats after Damage to the Hippocampus

Abstract: Rats with radio-frequency or ibotenic acid lesions of the hippocampus and rats with radio-frequency lesions of the fornix were tested on the visual paired comparison task (VPC), a test of recognition memory. Memory was assessed at five different delay intervals ranging from 10 sec to 24 hr. All operated groups performed normally at the shorter delays (10 sec and 1 min). Across longer delays, the two groups with hippocampal damage were impaired. Rats with fornix lesions performed well on the VPC task but were impaired on a spatial task (spontaneous alternation). The results show that the hippocampus is essential for normal recognition memory. Moreover, fornix lesions need not mimic the effects of direct damage to hippocampal tissue. The findings are discussed in the context of the contribution of the hippocampus to recognition memory.

Consequences of Driving Cessation Decreased Out-of-Home Activity Levels

Abstract: OBJECTIVES: Increasing age, socioeconomic factors, and declining function and health have been linked to driving cessation, but little is known about the consequences of stopping driving. This study was designed to test the hypothesis that driving cessation leads to a decline in out-of-home activity levels. METHODS: In 1989 a survey of driving practices was administered to surviving noninstitutionalized members of the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE) cohort. Of 1,316 respondents, 502 were active drivers as of 1988, 92 had stopped driving between 1982 and 1987, and 722 never drove or stopped before 1982. Information on sociodemographic and health-related variables came from in-home EPESE interviews in 1982, 1985, and 1988, and from yearly phone interviews. Activity was measured at all three in-home interviews, and an activity measure was created based on self-reported participation in nine out-of-home activities. A repeated measures random-effects model was used to test the effect of driving cessation on activity while controlling for potential confounders. RESULTS: Driving cessation was strongly associated with decreased out-of-home activity levels (coefficient-1.081, standard error 0.264, p Language: en

The Aneurysm Detection and Management Study Screening Program Validation Cohort and Final Results

Abstract: Background We previously reported the prevalence and associations of abdominal aortic aneurysm (AAA) in 73,451 veterans aged 50 to 79 years who underwent ultrasound screening. Objective To understand the prevalence of and principal positive and negative risk factors for AAA, and to assess reproducibility of our previous findings. Methods In the new cohort of veterans undergoing screening, 52,745 subjects aged 50 to 79 without history of AAA underwent successful ultrasound screening for AAA, after completing a questionnaire on demographics and potential risk factors. Results We detected AAA of 4.0 cm or larger in 613 participants (1.2%; compared with 1.4% in the earlier cohort). The direction and magnitude of the important associations reported in the first cohort were confirmed. Respective odds ratios for the major associations with AAA for the second and for the combined cohorts were as follows: 1.81 and 1.71 for age (per 7 years), 0.12 and 0.18 for female sex, 0.59 and 0.53 for black race, 1.94 and 1.94 for family history of AAA, 4.45 and 5.07 for smoking, 0.50 and 0.52 for diabetes, and 1.60 and 1.66 for atherosclerotic diseases. The excess prevalence associated with smoking accounted for 75% of all AAAs of 4.0 cm or larger in the total population of 126,196. Associations for AAA of 3.0 to 3.9 cm were similar but tended to be somewhat weaker. Conclusions Our findings confirm our previous cohort findings. Age, smoking, family history of AAA, and atherosclerotic diseases remained the principal positive associations with AAA, and female sex, diabetes, and black race remained the principal negative associations.

Delineation of a CpG Phosphorothioate Oligodeoxynucleotide for Activating Primate Immune Responses In Vitro and In Vivo

Abstract: Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides within specific sequence contexts (CpG motifs) are detected, like bacterial or viral DNA, as a danger signal by the vertebrate immune system. CpG ODN synthesized with a nuclease-resistant phosphorothioate backbone have been shown to be potent Th1-directed adjuvants in mice, but these motifs have been relatively inactive on primate leukocytes in vitro. Moreover, in vitro assays that predict in vivo adjuvant activity for primates have not been reported. In the present study we tested a panel of CpG ODN for their in vitro and in vivo immune effects in mice and identified in vitro activation of B and NK cells as excellent predictors of in vivo adjuvant activity. Therefore, we tested >250 phosphorothioate ODN for their capacity to stimulate proliferation and CD86 expression of human B cells and to induce lytic activity and CD69 expression of human NK cells. These studies revealed that the sequence, number, and spacing of individual CpG motifs contribute to the immunostimulatory activity of a CpG phosphorothioate ODN. An ODN with a TpC dinucleotide at the 5' end followed by three 6 mer CpG motifs (5'-GTCGTT-3') separated by TpT dinucleotides consistently showed the highest activity for human, chimpanzee, and rhesus monkey leukocytes. Chimpanzees or monkeys vaccinated once against hepatitis B with this CpG ODN adjuvant developed 15 times higher anti-hepatitis B Ab titers than those receiving vaccine alone. In conclusion, we report an optimal human CpG motif for phosphorothioate ODN that is a candidate human vaccine adjuvant.