Effects of coinfection with HIV and hepatitis C virus on the nervous system.

We evaluated a cohort of persons with late-stage HIV infection currently enrolled in a longitudinal tracking study to determine whether coinfection with hepatitis C virus (HCV) is associated with a greater prevalence and/or severity of HIV-associated cognitive-motor complex and distal predominantly sensory peripheral polyneuropathy compared with persons with HIV infection alone. Of 159 subjects, 31 tested positive for HCV, and this group was compared with 31 randomly selected subjects with HIV infection alone. All subjects underwent a structured neurological examination and a formal neuropsychological testing battery. Blood and cerebrospinal fluid samples were analyzed for cryoglobulins and glutamine levels, respectively. HIV/HCV-coinfected subjects showed a greater, statistically significant cognitive-motor impairment compared with those not coinfected. Despite the well-recognized neurological manifestations of both HIV infections and more recently hepatitis C, it is still uncertain whether the effects of HIV and HCV augment one another or are partially additive in their deleterious effects on the nervous system.

Longitudinally preserved psychomotor performance in long-term asymptomatic HIV-infected individuals.

BACKGROUND: Recent case reports have suggested that some asymptomatic HIV-infected individuals can develop CNS disturbances despite intact immunologic functioning and long-term suppression of plasma HIV concentrations to undetectable levels. This possibility has not yet been systematically studied longitudinally. METHODS: Using longitudinal data from the Multicenter AIDS Cohort Study, we investigated neuropsychological performance in long-term asymptomatic HIV-infected men who have sex with men. Performance over a 5-year period on the Symbol Digit Modalities test and the Trail Making Tests were compared in three HIV-positive asymptomatic groups [defined as 1) highly active antiretroviral therapy (HAART) treated with undetectable viral loads (n = 83), 2) AIDS-free for more than 15 years without HAART (n = 29), and 3) absence of clinical AIDS or CD4(+) lymphocyte count below 200 cells/muL at the beginning and end of the study period (n = 233)] and in HIV-negative controls (n = 237). Data were analyzed using linear mixed models and proportional odds logistic regression modeling with generalized estimating equations. RESULTS: There was no evidence of performance differences or performance declines over the 5-year period of study in any of the three long-term asymptomatic groups as compared with the HIV-negative group in the Symbol Digit Modalities test or the Trail Making Tests. Performance decrements were, however, observed with increasing age in each of the tests administered, demonstrating that performance declines could be detected by these methods. CONCLUSIONS: Regardless of how long-term asymptomatic status was defined immunologically or virologically, neuropsychological test performances remained stable. These findings suggest that psychomotor speed is preserved over many years in HIV-infected individuals with controlled HIV viremia.

Stability of human immunodeficiency virus type 1 RNA in cerebrospinal fluid determined with the AMPLICOR HIV-1 MONITOR test, version 1.5 (ultrasensitive).

We evaluated the effects of time, temperature, freezing, and thawing on the cerebrospinal fluid viral load by using the Roche AMPLICOR HIV-1 MONITOR test, version 1.5 (ultrasensitive). While a statistically significant decrease from the baseline was observed at 24 h, but not at 6 or 12 h, and with one freeze-thaw cycle, all changes were within the range of intra-assay variability.

Predictors of length of stay after coronary stenting.

BACKGROUND: Postprocedure length of stay (LOS) remains an important determinant of medical costs after coronary stenting. Variables that predict LOS in this setting have not been well characterized. METHODS: We evaluated 359 consecutive patients who underwent coronary stenting with antiplatelet therapy. Sequential multiple linear regression (MLR) models were constructed with use of 4 types of variables to predict log-transformed LOS: preprocedure, intraprocedure, and postprocedure factors and adverse outcomes. RESULTS: Preprocedure factors alone explained more than one third of the variability in postprocedure LOS (adjusted R(2) = 0.37). The addition of procedural variables added little to the model (adjusted R(2) = 0.39). Entering nonoutcome postprocedure variables significantly enhanced the predictive capacity of the model, explaining more than half the variability in postprocedure LOS (adjusted R(2) = 0.54). In the final model, addition of outcome variables increased its predictive capacity only slightly (adjusted R(2) = 0.61). In this model, significant preprocedure factors included: myocardial infarction (MI) within 24 hours, MI within 1 to 30 days, women with peripheral vascular disease, intravenous heparin, and chronic atrial fibrillation. High-risk intervention was the only significant intraprocedure variable. Significant postprocedure factors included periprocedure ischemia; cerebrovascular accident or transient ischemic attack; treatment with intravenous heparin or nitroglycerin or intra-aortic balloon pump; and need for blood transfusion. Significant adverse outcomes included contrast nephropathy, gastrointestinal bleeding, arrhythmia, vascular complication, and repeat angiography. CONCLUSION: This prediction model identifies a number of potentially reversible factors responsible for prolonging LOS and may enable the development of more accurate risk-adjusted methods with which to improve or compare care.

Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study.

BACKGROUND: Lipid-lowering agents are known to reduce long-term mortality in patients with stable coronary disease or significant risk factors. However, the effect of lipid-lowering therapy on short-term mortality immediately after an acute coronary syndrome has not been determined. We did an observational study using data from two randomised trials to investigate this issue. METHODS: We used data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among patients with acute coronary syndromes who were discharged on lipid-lowering agents (n=3653) with those who were not (n=17,156). A propensity analysis was done to adjust for presumed selection biases in the prescription of lipid-lowering agents. FINDINGS: Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days (17 [0.5%] vs 179 [1.0%], hazard ratio 0.44 [95% CI 0.27-0.73], p=0.001) and at 6 months (63 [1.7%] vs 605 [3.5%], 0.48 [0.37-0.63], p<0.0001). After adjustment for the propensity to be prescribed lipid-lowering agents and other potential confounders, prescription of a lipid-lowering agent at discharge remained associated with a reduced risk of death at 6 months (0.67 [0.48-0.95], p=0.023). INTERPRETATION: Prescription of a lipid-lowering drug at hospital discharge was independently associated with reduced short-term mortality among patients after an acute coronary syndrome.

A randomized controlled trial of exercise to improve outcomes of acute hospitalization in older adults.

OBJECTIVE: Older adults hospitalized for nondisabling diagnoses can lose functional ability. Lack of exercise or physical activity during the acute illness and recovery may be contributory. This study evaluated whether increased exercise in hospital and afterward would shorten length of stay and improve physical function at 1 month. DESIGN: A randomized controlled trial. SETTING: A 700-bed community-based hospital with academic and teaching programs. PARTICIPANTS: Three hundred patients (mean age 78.2 years +/- 5.6) with nondisabling medical and surgical diagnoses who were admitted to an acute care hospital between December 1990 and April 1992. All patients had an expected length of stay 5 or more days, were ambulatory before admission, and were not expected to die within 12 months. INTERVENTION: A hospital-based general exercise program was administered to intervention patients along with encouragement to continue the program, self-administered, at home. MEASUREMENTS: The primary outcome was hospital length of stay. Secondary outcomes at 1 month post-discharge included measures of physical function and other general health indicators. RESULTS: There was no significant difference in length of stay between treatment and control groups controlling for baseline characteristics and diagnoses. The intervention was associated with better function in instrumental activities of daily living (beta = .433 (95% CI, 0.044-0.842)) at 1 month but no change in perceived general health status and other measures of physical function. CONCLUSIONS: An exercise program started during hospitalization and continued for 1 month did not shorten length of stay but did improve functional outcome at 1 month.

Effectiveness of preventive in-home geriatric assessment in well functioning, community-dwelling older people: secondary analysis of a randomized trial.

OBJECTIVES: To determine whether preventive in-home comprehensive geriatric assessment (CGA) prevents functional decline in community-dwelling older persons with different baseline functional status: (1) without any basic activities of daily living (BADL) dependency at baseline; and (2) without any instrumental ADL (IADL) and basic ADL dependency at baseline. DESIGN: Subgroup analyses of a 3-year randomized controlled trial. SETTING: The city of Santa Monica, California. PARTICIPANTS: Participants came from the original population (n = 414) of community-living older persons aged 75 years and older who participated in a trial testing the effectiveness of annual preventive in-home CGA. For the first subgroup analysis, we excluded subjects (n = 27) who were dependent in one or more BADL before randomization (final sample size, n = 387); for the second subgroup analysis, we excluded 93 additional subjects who were dependent in one or more IADL before randomization (final sample size, n = 294). INTERVENTION: Annual preventive in-home CGA, with quarterly home visits by gerontologic nurse practitioners, for 3 years. MEASUREMENTS: Functional status data were collected through yearly in-home interviews by independent observers. Subjects were classified as (1) independent in both BADL and IADL, (2) dependent in IADL but independent in BADL, or (3) dependent in both IADL and BADL. RESULTS: In both subgroup analyses, there was no difference in survival between intervention and control subjects. In the subgroup with no BADL impairment at baseline, intervention subjects spent significantly fewer days dependent in both BADL and IADL during each year of the study (5 days vs 14 days, P = .022; 13 vs 33, P = .016; and 19 vs 44, P = .014 for years 1, 2, and 3, respectively) and over all 3 years combined (36 days vs 92 days, P = .016) in bivariate analyses. In multivariate analyses, the intervention reduced time spent in complete (BADL and IADL) dependency (P = .028). In the subgroup of subjects without any IADL or BADL impairment at baseline, no significant differences were apparent in the number of days spent in complete independence and days spent in complete dependency. Intervention group subjects spent more days in partial dependency during Year 1 (24 days vs 9 days, P = .021), but the difference was not significant during Year 2 (47 vs 29, P = .088), Year 3 (49 vs 41, P = .370), and over all 3 years combined (120 vs 79, P = .123) as well as in multivariate analysis (P = .062). CONCLUSION: These findings support the hypothesis that in-home preventive visits delay the onset of disability in people without initial BADL impairment. Further studies in larger samples are needed to determine optimal intervention strategies and effectiveness among well functioning older people.

Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging.

PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.

Cerebral toxoplasmosis and lymphoma in AIDS: perfusion MR imaging experience in 13 patients.

PURPOSE: To evaluate the perfusion magnetic resonance (MR) imaging characteristics of cerebral toxoplasmosis and lymphoma in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Perfusion MR imaging was performed prospectively in 13 patients with AIDS who had contrast material-enhancing focal brain lesions (six with active lymphoma, five with toxoplasmosis, one with treated lymphoma in remission, and one with toxoplasmosis plus lymphomatoid granulomatosis). Regional cerebral blood volume (rCBV) was determined by using dynamic echo-planar MR imaging during bolus injection of a gadolinium chelate. RESULTS: The rCBV was decreased (44% +/- 24 [standard deviation] of rCBV in the contralateral regions) throughout the toxoplasmosis lesions and in the surrounding edema of both lesion types, whereas all active lymphomas displayed areas of increased rCBV (258% +/- 99). These differences were significant (P < .005). CONCLUSION: Reduced rCBV i toxoplasmosis lesions is probably due to a lack of vasculature within the abscess; increased rCBV in lymphomas is probably due to hypervascularity in foci of active tumor growth; and decreased rCBV in the edema is probably due to vasoconstriction associated with increased interstitial pressure. Perfusion MR imaging is a rapid, noninvasive tool that may allow differentiation between cerebral lymphoma and toxoplasmosis in patients with AIDS.

The association between chronic illness and functional change among participants in a comprehensive geriatric assessment program.

OBJECTIVE: To examine the association between chronic illness and functional status change during a 3-year period in older people enrolled in an in-home comprehensive geriatric assessment (CGA) and preventive care program. DESIGN: Secondary analysis of data from a longitudinal cohort study. SETTING: Santa Monica, California. PARTICIPANTS: Two hundred two community-dwelling older persons (mean age at baseline was 81 years, 70% were women, and 72% reported good health) randomized to the intervention group in a trial of in-home comprehensive geriatric assessment and preventive care. MEASUREMENTS: We studied 13 common chronic illnesses/conditions determined clinically from an annual comprehensive evaluation by gerontologic nurse practitioners (GNPs) in consultation with study geriatricians. These target conditions included hypertension, osteoarthritis, coronary artery disease, obesity, undernutrition, urinary incontinence, sleep disorders, falls, gait/balance disorders, hearing and vision deficits, depression, and unsafe home environment. The dependent variable was functional change as measured by instrumental activities of daily living (IADL) and basic activities of daily living (BADL) assessed at baseline and annually for 3 years by independent research personnel. Potential confounding variables, including comorbid conditions and other subject characteristics, were controlled for in the analyses. RESULTS: Although functional status was similar at baseline, the presence of certain target conditions in this sample was associated significantly with functional decline in IADL and BADL during the 3-year period. Four conditions (gait/balance disorders, depression, unsafe home environment, and coronary artery disease) were associated with significant declines in IADL, and four conditions (gait/balance disorders, depression, hypertension, and urinary incontinence) were associated with significant declines in BADL. Conversely, subjects with obesity had no significant change in IADL or BADL throughout the study period and had less decline in IADL compared with nonobese subjects. CONCLUSIONS: Certain chronic conditions, particularly gait/balance disorders and depression, are associated with significant decline in functional status in older persons who receive CGA. These findings may help identify older persons at risk for greatest functional decline despite participation in CGA and may also suggest the need for more effective intervention strategies in these individuals.

Molecular and pathologic characterization of an AIDS-related body cavity-based lymphoma, including ultrastructural demonstration of human herpesvirus-8: a case report.

Body cavity-based lymphoma, also known as primary effusion lymphoma, is a newly recognized acquired immunodeficiency syndrome (AIDS)-related lymphoma that has been linked to the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). To date, direct visualization of the virus in a clinical sample has not been demonstrated. We have performed an extensive clinical, histologic, immunophenotypic, ultrastructural, and molecular genetic correlative study on multiple tissue samples obtained premortem and at autopsy from an patient with AIDS with Kaposi's sarcoma and body cavity-based lymphomas. We demonstrate the presence of human herpesvirus-8 in a primary clinical sample at the ultrastructural and molecular level, as well as document multiple lymphomatous tumor masses at autopsy.

The process of care in preventive in-home comprehensive geriatric assessment.

OBJECTIVES: To describe the process of care of a program of in-home comprehensive geriatric assessment (CGA) and to determine: (1) if there are major findings in all domains of CGA (medical, functional, mental health, and social/ environmental), (2) if there is a continued clinical yield when CGA is repeated annually, and (3) factors that affect patient adherence with recommendations from CGA. DESIGN: Descriptive prospective study of subjects allocated to the intervention group of a 3-year randomized trial of preventive in-home CGA. SETTING: Homes of participants living in an urban setting. PARTICIPANTS: Persons aged 75 years or older and living at home who received the intervention (N = 202 subjects, mean age 80.8 years, 70% female, 95% white, 64% living alone). INTERVENTION: Annual in-home CGA and quarterly home visits by gerontologic nurse practitioners for 3 years. MEASUREMENTS: Detailed data were collected prospectively on clinical problems detected by CGA, and specific recommendations were made for these problems using an instrument developed explicitly for this project to study the CGA process. Subject adherence with these recommendations was also recorded. RESULTS: Major problems were identified in all domains of CGA; the most common problems were medical. In the first year, 76.7% of subjects had at least one major problem identified that was either previously unknown or suboptimally treated. One-third of subjects had additional major problems identified during the second and third years. A constant number of therapeutic and preventive recommendations was made each year (11.5 per subject annually). Subject adherence varied by type of recommendation (ANOVA, F = 108.4, P < .001); adherence was better for referrals to a physician than for referrals to a non-physician professional or community service or for recommendations involving self-care activities (Scheffe's test, P < .001). CONCLUSION: In these community-dwelling older people, there was a continued yield of problems identified and recommendations made when CGA was repeated annually for 3 years, supporting the practice of repeat CGA in older people in the community. Subject adherence with recommendations from CGA varied by type of recommendation, but further work is needed to determine additional factors that affect this adherence and to determine the association between the yield of CGA (i.e., problems identified, recommendations given and adherence with these recommendations) and important clinical outcomes.

Metabolite abnormalities in progressive multifocal leukoencephalopathy by proton magnetic resonance spectroscopy.

OBJECTIVE: To evaluate progressive multifocal leukoencephalopathy (PML) lesions using proton magnetic resonance spectroscopy (1H MRS). DESIGN: CSF polymerase chain reaction (PCR) detection for JC viral (JCV) DNA; MRI and localized 1H MRS in the PML lesions, normal-appearing contralateral brain regions (CONTRA), and in matched brain regions of normal subjects. SETTING: University-affiliated medical center. PATIENTS OR PARTICIPANTS: 20 AIDS patients with clinical diagnosis of PML, 16 had tissue and/or CSF evidence of JCV infection; 20 age-matched normal subjects. MAIN OUTCOME MEASURES: Metabolites from 1H MRS: N-acetyl aspartate (NA), creatine (CR), choline-containing compounds (CHO), myoinositol (MI), glutamine/glutamate (GLX), lactate, and lipids. RESULTS: CSF PCR for JCV DNA showed 86% sensitivity. MRI showed characteristic demyelinating lesions; commonest locations were frontal lobe and cerebellum. 1H MRS in the lesions showed decreased NA (-35%; p < 0.0001) and CR (-18%; p = 0.003), increased CHO (+28%; p = 0.0005), occasional increased MI, and excess lactate (15/20 lesions) and lipids (18/20). In the CONTRA, MRS showed trends for increased CR (+15%), CHO (+15%), MI (+13%), and lower GLX (-9%; p = 0.02). Six patients, studied longitudinally (4-18 months), showed progressive spectroscopic changes; two patients with longest survival showed the highest MI. CONCLUSIONS: These MRS findings are consistent with neuropathologic observations of neuronal loss, cell membrane and myelin breakdown, and increased glial activity in PML lesions. The CONTRA abnormalities may be due to remote effects of PML or direct HIV-1 infection. 1H MRS may be useful for characterization and follow-up evaluation of PML lesions.

Silent ischemic cardiomyopathy and left coronary ostial stenosis secondary to radiation therapy.

A 55-year-old woman presented with profound congestive heart failure 23 years following mediastinal radiation. Ejection fraction (EF) was 35%. Symptoms markedly improved and EF increased to > 55% following saphenous vein bypass for > or = 80% ostial left main stenosis. Radiation therapy, a known risk factor for coronary atherosclerosis, may present with reversible severe silent ischemia.

Measuring psychosocial aspects of well-being in older community residents: performance of four short scales.

Given that the assessment of multiple dimensions of health/well-being can create respondent burden, assessment scales that are both effective and brief hold great attraction. In this study, we used Cronbach's alpha and correlational methods, including factor analysis, to evaluate the performance of four short scales measuring psychosocial aspects of well-being (depression, quality of life, sense of coherence, social support) in two samples of community-dwelling persons aged 75 and over (n = 414, n = 50). All four scales exhibited good range, high internal consistency, strong temporal reliability, and reasonable levels of construct validity. We conclude that they are practical contributors to measuring health in community-based older adults.

Brain lesions in patients with AIDS: H-1 MR spectroscopy.

PURPOSE: To evaluate the role of proton (hydrogen-1) magnetic resonance (MR) spectroscopy in the differential diagnosis of focal brain lesions in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Twenty-six men with 35 AIDS-related brain lesions underwent MR imaging and localized H-1 MR spectroscopy. Lesions consisted of 11 toxoplasmic abscesses, 12 progressive multifocal leukoencephalopathic lesions, eight lymphomas, and four cryptococcomas. Metabolite peak areas in the lesions were compared with those in the contralateral hemisphere in each patient. RESULTS: H-1 MR spectroscopic findings showed significantly different biochemical profiles for each diagnostic group (P = .0001) with regard to N-acetyl compounds, total creatine pool, choline-containing compounds, myoinositol, and lactate. H-1 MR spectroscopy alone helped correctly diagnose 94% (84% with jackknifed classification) of the brain lesions, without overlap between toxoplasmosis and lymphoma. CONCLUSION: H-1 MR spectroscopy is a sensitive and potentially specific noninvasive adjunctive method for differential diagnosis of focal brain lesions in AIDS.

A trial of annual in-home comprehensive geriatric assessments for elderly people living in the community.

BACKGROUND AND METHODS: The prevention of disability in elderly people poses a challenge for health care and social services. We conducted a three-year, randomized, controlled trial of the effect of annual in-home comprehensive geriatric assessment and follow-up for people living in the community who were 75 years of age or older. The 215 people in the intervention group were seen at home by gerontologic nurse practitioners who, in collaboration with geriatricians, evaluated problems and risk factors for disability, gave specific recommendations, and provided health education. The 199 people in the control group received their regular medical care. The main outcome measures were the prevention of disability, defined as the need for assistance in performing the basic activities of daily living (bathing, dressing, feeding, grooming, transferring from bed to chair, and moving around inside the house) or the instrumental activities of daily living (e.g., cooking, handling finances and medication, housekeeping, and shopping), and the prevention of nursing home admissions. RESULTS: At three years, 20 people in the intervention group (12 percent of 170 surviving participants) and 32 in the control group (22 percent of 147 surviving participants) required assistance in performing the basic activities of daily living (adjusted odds ratio, 0.4; 95 percent confidence interval, 0.2 to 0.8; P = 0.02). The number of persons who were dependent on assistance in performing the instrumental activities of daily living but not the basic activities did not differ significantly between the two groups. Nine people in the intervention group (4 percent) and 20 in the control group (10 percent) were permanently admitted to nursing homes (P = 0.02). Acute care hospital admissions and short-term nursing home admissions did not differ significantly between the two groups. In the second and third years of the study, there were significantly more visits to physicians among the participants in the intervention group than among those in the control group (mean number of visits per month, 1.41 in year 2 and 1.27 in year 3 in the intervention group, as compared with 1.11 and 0.92 visits, respectively, in the control group; P = 0.007 and P = 0.001, respectively). The cost of the intervention for each year of disability-free life gained was about $46,000. CONCLUSIONS: A program of in-home comprehensive geriatric assessments can delay the development of disability and reduce permanent nursing home stays among elderly people living at home.