Showing papers by "Veterans Health Administration published in 2003"

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis.

Abstract: A review of 2,647 studies of posttraumatic stress disorder (PTSD) yielded 476 potential candidates for a meta-analysis of predictors of PTSD or of its symptoms. From these, 68 studies met criteria for inclusion in a meta-analysis of 7 predictors: (a) prior trauma, (b) prior psychological adjustment, (c) family history of psychopathology, (d) perceived life threat during the trauma, (e) posttrauma social support, (f) peritraumatic emotional responses, and (g) peritraumatic dissociation. All yielded significant effect sizes, with family history, prior trauma, and prior adjustment the smallest (weighted r = .17) and peritraumatic dissociation the largest (weighted r = .35). The results suggest that peritraumatic psychological processes, not prior characteristics, are the strongest predictors of PTSD.

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Abstract: Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

A randomized trial of aspirin to prevent colorectal adenomas

Abstract: Background Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel. Methods We performed a randomized, double-blind trial of aspirin as a chemopreventive agent against colorectal adenomas. We randomly assigned 1121 patients with a recent history of histologically documented adenomas to receive placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients) daily. According to the protocol, follow-up colonoscopy was to be performed approximately three years after the qualifying endoscopy. We compared the groups with respect to the risk of one or more neoplasms (adenomas or colorectal cancer) at least one year after randomization using generalized linear models to compute risk ratios and 95 percent confidence intervals. Results Reported adherence to study medications and avoidance of nonsteroidal antiinflammatory drugs were excellent. Follow-up colonoscopy was performed at least one year after randomization in 1084 patients (97 perc...

Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade Compared With Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Intervention: REPLACE-2 Randomized Trial

Abstract: ContextThe direct thrombin inhibitor bivalirudin has been associated with better efficacy and less bleeding than heparin during coronary balloon angioplasty but has not been widely tested during contemporary percutaneous coronary intervention (PCI).ObjectiveTo determine the efficacy of bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI, compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection from periprocedural ischemic and hemorrhagic complications.Design, Setting, and ParticipantsThe Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)–2 trial, a randomized, double-blind, active-controlled trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002.InterventionsPatients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition (n = 2999), or heparin (65-U/kg bolus) with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n = 3011). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI.Main Outcome MeasuresThe primary composite end point was 30-day incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding; the secondary composite end point was 30-day incidence of death, myocardial infarction, or urgent repeat revascularization.ResultsProvisional Gp IIb/IIIa blockade was administered to 7.2% of patients in the bivalirudin group. By 30 days, the primary composite end point had occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients in the heparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval, 0.77-1.09; P = .32). The secondary composite end point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval 0.90-1.32; P = .40). Prespecified statistical criteria for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end points. In-hospital major bleeding rates were significantly reduced by bivalirudin (2.4% vs 4.1%; P<.001).ConclusionsBivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Gp IIb/IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding.

The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development

Abstract: The cholinergic hypothesis was initially presented over 20 years ago and suggests that a dysfunction of acetylcholine containing neurons in the brain contributes substantially to the cognitive decline observed in those with advanced age and Alzheimer's disease (AD). This premise has since served as the basis for the majority of treatment strategies and drug development approaches for AD to date. Recent studies of the brains of patients who had mild cognitive impairment or early stage AD in which choline acetyltransferase and/or acetylcholinesterase activity was unaffected (or even up-regulated) have, however, led some to challenge the validity of the hypothesis as well as the rationale for using cholinomimetics to treat the disorder, particularly in the earlier stages. These challenges, primarily based on assays of post mortem enzyme activity, should be taken in perspective and evaluated within the wide range of cholinergic abnormalities known to exist in both aging and AD. The results of both post mortem and antemortem studies in aged humans and AD patients, as well as animal experiments suggest that a host of cholinergic abnormalities including alterations in choline transport, acetylcholine release, nicotinic and muscarinic receptor expression, neurotrophin support, and perhaps axonal transport may all contribute to cognitive abnormalities in aging and AD. Cholinergic abnormalities may also contribute to noncognitive behavioral abnormalities as well as the deposition of toxic neuritic plaques in AD. Therefore, cholinergic-based strategies will likely remain valid as one approach to rational drug development for the treatment of AD other forms of dementia.

Traces of human migrations in Helicobacter pylori populations

Abstract: Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.

Alport's Syndrome, Goodpasture's Syndrome, and Type IV Collagen

Abstract: Defects in type IV collagen, a collagenous protein involved in the formation of basement membranes, have been implicated in hereditary Alport's syndrome and acquired Goodpasture's syndrome. Mutations in genes corresponding to the building blocks of type IV collagen cause Alport's syndrome, whereas autoantibodies against structures that are usually hidden in the recesses of collagen IV cause Goodpasture's syndrome.

A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients.

Abstract: We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials.

Weight Bias among Health Professionals Specializing in Obesity

Abstract: SCHWARTZ, MARLENE B., HEATHER O’NEAL CHAMBLISS, KELLY D. BROWNELL, STEVEN N. BLAIR, AND CHARLES BILLINGTON. Weight bias among health professionals specializing in obesity. Obes Res. 2003;11:1033–1039. Purpose: To determine the level of anti-fat bias in health professionals specializing in obesity and identify personal characteristics that correlate with both implicit and explicit bias. Research Methods and Procedures: The Implicit Associations Test (IAT) and a self-report questionnaire assessing explicit attitudes, personal experiences with obesity, and demographic characteristics was administered to clinicians and researchers attending the opening session of an international obesity conference (N 389). The IAT was used to assess overall implicit weight bias (associating “obese people” and “thin people” with “good” vs. “bad”) and three ranges of stereotypes: lazy-motivated, smart-stupid, and valuable-worthless. The questionnaire assessed explicit bias on the same dimensions, along with personal and professional experiences with obesity. Results: Health professionals exhibited a significant prothin, anti-fat implicit bias on the IAT. In addition, the subjects significantly endorsed the implicit stereotypes of lazy, stupid, and worthless using the IAT. Level of bias was associated with several personal characteristics. Characteristics significantly predictive of lower levels of implicit anti-fat bias include being male, older, having a positive emotional outlook on life, weighing more, having friends who are obese, and indicating an understanding of the experience of obesity. Discussion: Even professionals whose careers emphasize research or the clinical management of obesity show very strong weight bias, indicating pervasive and powerful stigma. Understanding the extent of anti-fat bias and the personal characteristics associated with it will aid in developing intervention strategies to ameliorate these damaging attitudes.

Myelin Oligodendrocyte Glycoprotein–specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis

Abstract: Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.

Depressive symptoms and health-related quality of life: the Heart and Soul Study.

Abstract: ContextLittle is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease.ObjectiveTo compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease.Design, Setting, and ParticipantsCross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002.Main MeasuresMeasurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor.ResultsOf the 1024 participants, 201 (20%) had depressive symptoms (PHQ score ≥10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P = .002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not.ConclusionsAmong patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function—ejection fraction and ischemia—are not. Efforts to improve health status should include assessment and treatment of depressive symptoms.

Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging

Abstract: Mice heterozygous for the Sod2 gene (Sod2+/− mice) have been used to study the phenotype of life-long reduced Mn-superoxide dismutase (MnSOD) activity. The Sod2+/− mice have reduced MnSOD activity ...

Histone Deacetylase Inhibition by Sodium Butyrate Chemotherapy Ameliorates the Neurodegenerative Phenotype in Huntington's Disease Mice

Abstract: The precise cause of neuronal death in Huntington's disease (HD) is unknown. Although no single specific protein-protein interaction of mutant huntingtin has emerged as the pathologic trigger, transcriptional dysfunction may contribute to the neurodegeneration observed in HD. Pharmacological treatment using the histone deacetylase inhibitor sodium butyrate to modulate transcription significantly extended survival in a dose-dependent manner, improved body weight and motor performance, and delayed the neuropathological sequelae in the R6/2 transgenic mouse model of HD. Sodium butyrate also increased histone and Specificity protein-1 acetylation and protected against 3-nitropropionic acid neurotoxicity. Microarray analysis showed increased expression of α- and β-globins and MAP kinase phosphatase-1 in sodium butyrate-treated R6/2 mice, indicative of improved oxidative phosphorylation and transcriptional regulation. These findings strengthen the hypothesis that transcriptional dysfunction plays a role in the pathogenesis of HD and suggest that therapies aimed at modulating transcription may target early pathological events and provide clinical benefits to HD patients.

Cardiovascular reactivity and development of preclinical and clinical disease states

Abstract: OBJECTIVE The objective of this review is to evaluate the evidence for the hypothesis that cardiovascular reactivity can predict the development of preclinical (elevated blood pressure, ventricular remodeling, carotid atherosclerosis) and/or clinical cardiovascular disease states. METHODS A review of the literature was conducted examining prospective studies. RESULTS Three large epidemiological studies with long-term follow-up periods (20 years or more) have found blood pressure responses to the cold pressor task to be predictive of subsequent essential hypertension in initially normotensive samples. Studies showing less consistent results have tended to use shorter-term follow-up periods. A larger body of literature demonstrates consistent associations between stress-related cardiovascular reactivity and blood pressure elevations in youth over the course of 1 to 6 years; such relationships have not been consistently shown among adult samples. Moderately consistent evidence points to a positive relationship between reactivity and other measures of subclinical disease (increased left ventricular mass and carotid atherosclerosis) among the few prospective studies that have examined these issues to date. A number of additional factors, however, such as baseline levels of disease risk and exposure to psychosocial stress, seem to moderate these relationships. Health status at baseline also seems to moderate the association between reactivity and clinical coronary heart disease in recent reports: two of three existing studies in initially healthy samples show no evidence of a relationship between reactivity and clinical outcomes, whereas three of four studies in samples with preexisting coronary heart disease or essential hypertension show a positive relationship between reactivity and subsequent disease states. CONCLUSIONS There is reasonable evidence to suggest that cardiovascular reactivity can predict the development of some preclinical states (eg, increased left ventricular mass and blood pressure) states and perhaps even new clinical events in some patients with essential hypertension or coronary heart disease. However, much more information is needed concerning moderating and potentially confounding variables before the robustness of the positive relationships can become clinically useful.

Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis—State of the Art: Cystic Fibrosis Foundation Consensus Conference

Abstract: Because of the difficulties of recognizing allergic bronchopulmonary aspergillosis (ABPA) in the context of cystic fibrosis (because of overlapping clinical, radiographic, microbiologic, and immunologic features), advances in our understanding of the pathogenesis of allergic aspergillosis, new possibilities in therapy, and the need for agreed-upon definitions, an international consensus conference was convened. Areas addressed included fungal biology, immunopathogenesis, insights from animal models, diagnostic criteria, epidemiology, the use of new immunologic and genetic techniques in diagnosis, imaging modalities, pharmacology, and treatment approaches. Evidence from the existing literature was graded, and the consensus views were synthesized into this document and recirculated for affirmation. Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified. New information has come from transgenic animals and recombinant fungal and host molecules. Diagnostic criteria that could provide a framework for monitoring were adopted, and helpful imaging features were identified. New possibilities in therapy produced plans for managing diverse clinical presentations.

Effect of the Transformation of the Veterans Affairs Health Care System on the Quality of Care

Abstract: Background In the mid-1990s, the Department of Veterans Affairs (VA) health care system initiated a systemwide reengineering to, among other things, improve its quality of care. We sought to determine the subsequent change in the quality of health care and to compare the quality with that of the Medicare fee-for-service program. Methods Using data from an ongoing performance-evaluation program in the VA, we evaluated the quality of preventive, acute, and chronic care. We assessed the change in quality-of-care indicators from 1994 (before reengineering) through 2000 and compared the quality of care with that afforded by the Medicare fee-for-service system, using the same indicators of quality. Results In fiscal year 2000, throughout the VA system, the percentage of patients receiving appropriate care was 90 percent or greater for 9 of 17 quality-of-care indicators and exceeded 70 percent for 13 of 17 indicators. There were statistically significant improvements in quality from 1994–1995 through 2000 for al...

Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2

Abstract: Stimulation of a mutant angiotensin type 1A receptor (DRY/AAY) with angiotensin II (Ang II) or of a wild-type receptor with an Ang II analog ([sarcosine1,Ile4,Ile8]Ang II) fails to activate classical heterotrimeric G protein signaling but does lead to recruitment of β-arrestin 2-GFP and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (maximum stimulation ≈50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular β-arrestin 2 but is unaffected by the PKC inhibitor Ro-31-8425. In parallel, stimulation of the wild-type angiotensin type 1A receptor with Ang II robustly stimulates ERK1/2 activation with ≈60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular β-arrestin 2 by small interfering RNA (β-arrestin dependent). These findings imply the existence of independent G protein- and β-arrestin 2-mediated pathways leading to ERK1/2 activation and the existence of distinct “active” conformations of a seven-membrane-spanning receptor coupled to each.

Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection.

Abstract: Background Metabolic abnormalities associated with human immunodeficiency virus (HIV) infection, including dysglycemia and hyperlipidemia, are increasingly prevalent, and there is concern about the possibility of an association with accelerated cardiovascular and cerebrovascular disease. Methods We conducted a retrospective study of the risk of cardiovascular and cerebrovascular disease among the 36,766 patients who received care for HIV infection at Veterans Affairs facilities between January 1993 and June 2001. Results For antiretroviral therapy, 70.2 percent of the patients received nucleoside analogues, 41.6 percent received protease inhibitors, and 25.6 percent received nonnucleoside reverse-transcriptase inhibitors for a median of 17 months, 16 months, and 9 months, respectively. Approximately 1000 patients received combination therapy with a protease inhibitor for at least 48 months, and approximately 1000 patients received combination therapy with a nonnucleoside reverse-transcriptase inhibitor fo...

Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis.

Abstract: Positron emission tomography with 18-fluorodeoxyglucose is more accurate than computed tomography for mediastinal staging. However, it is more sensitive but less specific when computed tomography s...

Paved With Good Intentions: Do Public Health and Human Service Providers Contribute to Racial/Ethnic Disparities in Health?

Abstract: There is extensive evidence of racial/ethnic disparities in receipt of health care. The potential contribution of provider behavior to such disparities has remained largely unexplored. Do health and human service providers behave in ways that contribute to systematic inequities in care and outcomes? If so, why does this occur? The authors build on existing evidence to provide an integrated, coherent, and sound approach to research on providers’ contributions to racial/ethnic disparities. They review the evidence regarding provider contributions to disparities in outcomes and describe a causal model representing an integrated set of hypothesized mechanisms through which health care providers’ behaviors may contribute to these disparities.

An Unfolded Map of the Cerebellar Dentate Nucleus and its Projections to the Cerebral Cortex

Abstract: We have used retrograde transneuronal transport of neurotropic viruses to examine the organization of the projections from the dentate nucleus of the cerebellum to “motor” and “nonmotor” areas of the cerebral cortex. To perform this analysis we created an unfolded map of the dentate. Plotting the results from current and prior experiments on this unfolded map revealed important features about the topography of function in the dentate. We found that the projections to the primary motor and premotor areas of the cerebral cortex originated from dorsal portions of the dentate. In contrast, projections to prefrontal and posterior parietal areas of cortex originated from ventral portions of the dentate. Thus the dentate contains anatomically separate and functionally distinct motor and nonmotor domains.

Aging and Genome Maintenance: Lessons from the Mouse?

Abstract: Recent progress in the science of aging is driven largely by the use of model systems, ranging from yeast and nematodes to mice. These models have revealed conservation in genetic pathways that balance energy production and its damaging by-products with pathways that preserve somatic maintenance. Maintaining genome integrity has emerged as a major factor in longevity and cell viability. Here we discuss the use of mouse models with defects in genome maintenance for understanding the molecular basis of aging in humans.

Randomized Clinical Trial of Therapeutic Exercise in Subacute Stroke

Abstract: Background and Purpose— Rehabilitation care after stroke is highly variable and increasingly shorter in duration. The effect of therapeutic exercise on impairments and functional limitations after stroke is not clear. The objective of this study was to determine whether a structured, progressive, physiologically based exercise program for subacute stroke produces gains greater than those attributable to spontaneous recovery and usual care. Methods— This randomized, controlled, single-blind clinical trial was conducted in a metropolitan area and 17 participating healthcare institutions. We included persons with stroke who were living in the community. One hundred patients (mean age, 70 years; mean Orpington score, 3.4) consented and were randomized from a screened sample of 582. Ninety-two subjects completed the trial. Intervention was a structured, progressive, physiologically based, therapist-supervised, in-home program of thirty-six 90-minute sessions over 12 weeks targeting flexibility, strength, balan...

Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone

Abstract: Background Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. Methods We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. Results The double-blind trial was terminated early because buprenorphine and naloxone in combination and ...