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Biomedical subjects

M B Goetz

Publications and source records attributed to M B Goetz.

At least 19 recordsLinked to original sources

Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity.

BACKGROUND: Although the use of highly active antiretroviral therapy in the treatment of HIV infection has led to considerable improvement in morbidity and mortality, unless patients are adherent to their drug regimen (i.e., at least 90 to 95% of doses taken), viral replication may ensue and drug-resistant strains of the virus may emerge. METHODS: The authors studied the extent to which neuropsychological compromise and medication regimen complexity are predictive of poor adherence in a convenience sample of 137 HIV-infected adults. Medication adherence was tracked through the use of electronic monitoring technology (MEMS caps). RESULTS: Two-way analysis of variance revealed that neurocognitive compromise as well as complex medication regimens were associated with significantly lower adherence rates. Cognitively compromised participants on more complex regimens had the greatest difficulty with adherence. Deficits in executive function, memory, and attention were associated with poor adherence. Logistic regression analysis demonstrated that neuropsychological compromise was associated with a 2.3 times greater risk of adherence failure. Older age (>50 years) was also found to be associated with significantly better adherence. CONCLUSIONS: HIV-infected adults with significant neurocognitive compromise are at risk for poor medication adherence, particularly if they have been prescribed a complex dosing regimen. As such, simpler dosing schedules for more cognitively impaired patients might improve adherence.

Adult↗

Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults.

In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with > or = 200 CD4 cells/microl received placebo (PL), 7-valent conjugate, or 23-valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart: conjugate-conjugate, conjugate-polysaccharide, placebo-polysaccharide, placebo-placebo. A total of 67 persons completed the study. Neither significant increases in HIV viral load nor severe adverse reactions occurred in any group. After controlling for confounders, when compared with persons receiving placebo-polysaccharide, persons receiving conjugate-conjugate and conjugate-polysaccharide had higher antibody concentrations (serotypes 4, 6B, 9V and serotype 23F, respectively) and opsonophagocytic titers (functional antibody assay, serotypes 9V, 23F and serotypes 4, 6B, 9V, respectively) after the second dose (P<0.05). The second dose with either conjugate or polysaccharide following the first conjugate dose, however, produced no further increase in immune responses.

Adult↗

Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy.

Among virological responders, the area under the curve of the CD4 count minus baseline (AUCMB) after 3, 9, 15 and 18 months of highly active antiretroviral therapy (HAART) was less in individuals 55 years or older (P < 0.05). Fewer older individuals achieved increases of 50, 100, or over 150 CD4 cells/l. A random quadratic time course model estimated that the AUCMB decreased 35 cells/year for each 10 years of additional age during the first 12 months after HAART (P < 0.005).

Aged↗

Using the national registry of HIV-infected veterans in research: lessons for the development of disease registries.

Disease-specific registries have many important applications in epidemiologic, clinical and health services research. Since 1989 the Department of Veterans Affairs has maintained a national HIV registry. VA's HIV registry is national in scope, it contains longitudinal data and detailed resource utilization and clinical information. To describe the structure, function, and limitations of VA's national HIV registry, and to test its accuracy and completeness. The VA's national HIV registry contains data that are electronically extracted from VA's computerized comprehensive clinical and administrative databases, called Veterans Integrated Health Systems Technology and Architecture (VISTA). We examined the number of AIDS patients and the number of new patients identified to the registry, by year, through December 1996. We verified data elements against information obtained from the medical records at five VA sites. By December 1996, 40,000 HIV-infected patients had been identified to the registry. We encountered missing data and problems with data classification. Missing data occurred for some elements related to the computer programming that creates the registry (e.g., pharmacy files), and for other elements because manual entry is required (e.g., ethnicity). Lack of a standardized data classification system was a problem, especially for the pharmacy and laboratory files. In using VA's national HIV registry we have learned important lessons, which, if taken into account in the future, could lead to the creation of model disease-specific registries.

HIV Infections↗

Evaluating quality indicators for patients with community-acquired pneumonia.

BACKGROUND: Several organizations have published evidence-based quality indicators for community-acquired pneumonia (CAP). However, there is variability in the types of indicators presented between organizations and the level of supporting evidence for each of the indicators. A systematic review of the literature and relevant Internet Web sites was performed to identify quality indicators for CAP that have been proposed or recommended by organizations, and each of the indicators was then critically appraised, using a well-defined set of criteria. METHODOLOGY: The MEDLINE, EMBASE, Best Evidence, and Cochrane Systematic Review databases and Internet Web sites were searched for articles and guidelines published between January 1980 and May 2001 to identify quality indicators for CAP and relevant evidence. Experts in the area of health services research were contacted to identify additional sources. A well-defined set of criteria was applied to evaluate each of the quality indicators. RESULTS: The systematic review of the literature and Internet Web sites yielded 44 CAP-specific quality indicators. The critical appraisal of these indicators yielded 16 indicators that were supported by a study that identified an association between quality of care and the process of care or outcome measure, were applied to enough patients to be able to detect clinically meaningful differences, were clinically and/or economically relevant, were measurable in a clinical practice setting, and were precise in their specifications. CONCLUSIONS: Many organizations recommend indicators for CAP. Indicators may serve as measures of clinical performance for clinicians and hospitals, may help in benchmarking, and may ultimately facilitate improvements in quality of care and cost reductions. However, CAP indicators often vary in their meaningfulness, scientific soundness, and interpretability of results. A set of five critical appraisal questions may assist in the evaluation of which quality indicators are most valid.

Community-Acquired Infections↗

HIV-related Pneumocystis carinii pneumonia in older patients hospitalized in the early HAART era.

OBJECTIVE: To determine whether older age continues to influence patterns of care and in-hospital mortality for hospitalized persons with HIV-related Pneumocystis carinii pneumonia (PCP), as determined in our prior study from the 1980s. DESIGN: Retrospective chart review. PATIENTS/SETTING: Patients (1,861) with HIV-related PCP at 78 hospitals in 8 cities from 1995 to 1997. MEASUREMENTS: Medical record notation of possible HIV infection; alveolar-arterial oxygen gradient; CD4 lymphocyte count; presence or absence of wasting; timely use of anti-PCP medications; in-hospital mortality. MAIN RESULTS: Compared to younger patients, patients > or =50 years of age were less likely to have HIV mentioned in their progress notes (70% vs 82%, P <.001), have mild or moderately severe PCP cases at admission (89% vs 96%, P <.002), receive anti-PCP medications within the first 2 days of hospitalization (86% vs 93%, P <.002), and survive hospitalization (82% vs 90%, P <.003). However, age was not a significant predictor of mortality after adjustment for severity of PCP and timeliness of therapy. CONCLUSIONS: While inpatient PCP mortality has improved by 50% in the past decade, 2-fold age-related mortality differences persist. As in the 1980s, these differences are associated with lower rates of recognition of HIV, increased severity of illness at admission, and delays in initiation of PCP-specific treatments among older individuals--factors suggestive of delayed recognition of HIV infection, pneumonia, and PCP, respectively. Continued vigilance for the possibility of HIV and HIV-related PCP among persons > or =50 years of age who present with new pulmonary symptoms should be encouraged.

AIDS-Related Opportunistic Infections↗

A new preadmission staging system for predicting inpatient mortality from HIV-associated Pneumocystis carinii pneumonia in the early highly active antiretroviral therapy (HAART) era.

A common severe complication of human immunodeficiency virus (HIV) infection has been Pneumocystis carinii pneumonia (PCP). Recently, with increasing use of PCP prophylaxis and multidrug antiretroviral therapy, the clinical manifestations of HIV infection have changed dramatically and the predictors of inpatient mortality for PCP may have also changed. We developed a new staging system for predicting inpatient mortality for patients with HIV-associated PCP admitted between 1995 and 1997. Trained abstractors performed chart reviews of 1,660 patients hospitalized with HIV-associated PCP between 1995 and 1997 at 78 hospitals in seven metropolitan areas in the United States. The overall inpatient mortality rate was 11.3%. Hierarchically optimal classification tree analysis identified an ordered five-category staging system based on three predictors: wasting, alveolar-arterial oxygen gradient (AaPO(2)), and serum albumin level. The mortality rate increased with stage: 3.7% for Stage 1, 8.5% for Stage 2, 16.1% for Stage 3, 23.3% for Stage 4, and 49.1% for Stage 5. This new staging system may be useful for severity of illness adjustment in the current era while exploring current variation in HIV-associated PCP inpatient mortality rates among hospitals and across cities.

AIDS-Related Opportunistic Infections↗

Delays in tuberculosis isolation and suspicion among persons hospitalized with HIV-related pneumonia.

BACKGROUND: Despite awareness of HIV-related tuberculosis (TB), nosocomial outbreaks of multidrug-resistant TB among HIV-infected individuals occur. OBJECTIVE: To investigate delays in TB isolation and suspicion among HIV-infected inpatients discharged with TB or Pneumocystis carinii pneumonia (PCP), common HIV-related pneumonias. DESIGN: Cohort study during 1995 to 1997. SETTING: For PCP, 1,227 persons who received care at 44 New York City, Chicago, and Los Angeles hospitals. For TB, 89 patients who received care at five Chicago hospitals. MEASUREMENTS: Two-day rates of TB isolation/suspicion. RESULTS: For HIV-related PCP, Los Angeles hospitals had the lowest 2-day rates of isolation/suspicion of TB (24.3%/26.6% vs 65.5%/66.4% for New York City and 62.8%/58.3% for Chicago, respectively; p < 0.001 for overall comparison by chi(2) test for each outcome measure). Within cities, hospital isolation/suspicion rates varied from < 35 to > 70% (p < 0.001 for interhospital comparisons in each city). The Chicago hospital with a nosocomial outbreak of multidrug-resistant TB from 1994 to 1995 isolated 60% of HIV-infected individuals who were discharged with a diagnosis of HIV-related TB and 52% discharged with HIV-related PCP, rates that were among the lowest of all Chicago hospitals in both data sets. CONCLUSION: Low 2-day rates of TB isolation/suspicion among HIV-related PCP patients were frequent. One Chicago hospital with low 2-day rates of TB isolation/suspicion among persons with HIV-related PCP also had low 2-day rates of isolation/suspicion among confirmed TB patients. That hospital experienced a nosocomial multidrug-resistant TB outbreak. Educational efforts on the benefits of early TB suspicion/isolation among HIV-infected pneumonia patients are needed.

AIDS-Related Opportunistic Infections↗

Improving pneumococcal vaccine rates. Nurse protocols versus clinical reminders.

OBJECTIVE: To compare the effectiveness of three interventions designed to improve the pneumococcal vaccination rate. DESIGN: A prospective controlled trial. SETTING: Department of Veterans Affairs ambulatory care clinic. PATIENTS/PARTICIPANTS: There were 3, 502 outpatients with scheduled visits divided into three clinic teams (A, B, or C). INTERVENTIONS: During a 12-week period, each clinic team received one intervention: (A) nurse standing orders with comparative feedback as well as patient and clinician reminders; (B) nurse standing orders with compliance reminders as well as patient and clinician reminders; and (C) patient and clinician reminders alone. Team A nurses (comparative feedback group) received information on their vaccine rates relative to those of team B nurses. Team B nurses (compliance reminders group) received reminders to vaccinate but no information on vaccine rates. MEASUREMENTS AND MAIN RESULTS: Team A nurses assessed more patients than team B nurses (39% vs 34%, p =.009). However, vaccination rates per total patient population were similar (22% vs 25%, p =.09). The vaccination rates for both team A and team B were significantly higher than the 5% vaccination rate for team C (p <.001). CONCLUSIONS: Nurse-initiated vaccine protocols raised vaccination rates substantially more than a physician and patient reminder system. The nurse-initiated protocol with comparative feedback modestly improved the assessment rate compared with the protocol with compliance reminders, but overall vaccination rates were similar.

Ambulatory Care Facilities↗

The significance of vitamin A and carotenoid status in persons infected by the human immunodeficiency virus.

Hyporetinemia is associated with increased childhood morbidity and mortality that is reversible with vitamin A supplementation. Although vitamin A deficiency is otherwise rare in developed countries, the prevalence of hyporetinemia in human immunodeficiency virus (HIV)-infected persons is up to 29%. Hyporetinemic HIV-infected patients have a 3.5-5-fold increased risk of death. Furthermore, HIV-infected patients with very low or very high intake of vitamin A and beta-carotene (a vitamin A precursor) have greater rates of disease progression than do patients with intermediate intake. In developing countries up to 60% of HIV-infected pregnant women are hyporetinemic. In such women the relative risk of perinatal HIV transmission may be increased more than fourfold. These data indicate that vitamin A deficiency is common in HIV-infected patients in the developed world and strongly suggest that vitamin A supplementation may be especially useful in adjunctive therapy for HIV-infected pregnant women who reside in the developing world.

Carotenoids↗

Effect of oral beta-carotene supplementation on plasma human immunodeficiency virus (HIV) RNA levels and CD4+ cell counts in HIV-infected patients.

We conducted a pilot, open-label study to assess the effect of short-term beta-carotene administration (180 mg/d with meals for 4 weeks) on the plasma human immunodeficiency virus (HIV) RNA levels and CD4+ lymphocyte counts in 21 HIV-infected patients. We found that plasma HIV RNA levels and CD4+ lymphocyte counts did not change following this short course of beta-carotene supplementation. Patients with lower serum concentrations of beta-carotene before supplementation were no more likely to have an increase in their CD4+ lymphocyte count or plasma HIV RNA copy number than were those with higher concentrations. No correlation was found between pre- or postsupplementation beta-carotene or vitamin A concentrations and pre- or postsupplementation CD4+ lymphocyte counts or plasma HIV RNA titers. This study provides no support for beta-carotene supplementation for HIV-infected subjects with normal baseline serum levels of beta-carotene and vitamin A.

Administration, Oral↗

Potential contributions of viral envelope and host genetic factors in a human immunodeficiency virus type 1-infected long-term survivor.

The lack of clinical progression in some individuals despite prolonged human immunodeficiency virus type 1 (HIV-1) infection may result from infection with less-pathogenic viral strains. To address this question, we examined the HIV-1 envelope protein from a donor with a low viral burden, stable CD4(+) T-lymphocyte counts, and little evidence of CD8(+) T-cell expansion, activation, or immune activity. To avoid potential changes in envelope function resulting from selection in vitro, envelope clones were constructed by using viral RNA isolated from uncultured peripheral blood mononuclear cells (PBMC). The data showed that recombinant viruses containing envelope sequences derived from RNA isolated from patient PBMC replicated poorly in primary CD4(+) T cells but demonstrated efficient growth in macrophages. The unusual phenotype of these viruses could not be explained solely by differential utilization of coreceptors since the chimeric viruses, as well as an uncloned isolate obtained from the same visit date, can utilize CCR5. In addition, the donor's own cells appeared resistant to infection with chimeric viruses containing autologous envelope sequences. Genotype analysis revealed that the donor was heterozygous for the previously described 32-bp deletion in CCR5 which may be linked with prolonged survival in HIV-1-infected individuals. These data suggest that the changes in envelope sequences confer properties of viral attenuation, which together with the CCR5 +/Delta32 genotype could account for the long-term survival of this patient.

Amino Acid Sequence↗

A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor.

The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell- tropic human immunodeficiency virus (HIV)-1 strains, whereas CCR5 is used by macrophage (M)-tropic strains. Here we show that a small-molecule inhibitor, ALX40-4C, inhibits HIV-1 envelope (Env)-mediated membrane fusion and viral entry directly at the level of coreceptor use. ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T- and dual-tropic HIV-1 strains, whereas use of CCR5 by M- and dual-tropic strains was not inhibited. Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressed CXCR4 alone. ALX40-4C blocked stromal-derived factor (SDF)-1alpha-mediated activation of CXCR4 and binding of the monoclonal antibody 12G5 to cells expressing CXCR4. Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion.

Anti-HIV Agents↗

Gender differences in early suspicion of tuberculosis in hospitalized, high-risk patients during 4 epidemic years, 1987 to 1990.

OBJECTIVES: To assess the degree to which, from 1987 to 1990, physicians suspected tuberculosis (TB) in the first 2 hospital days in human immunodeficiency virus (HIV)-infected patients with pulmonary disease. DESIGN: Retrospective cohort study. SETTING: 96 hospitals in five US cities. PATIENTS: 2,174 adult patients with acquired immunodeficiency syndrome discharged with a diagnosis of Pneumocystis carinii pneumonia from 1987 to 1990. The diagnosis generally was not known on admission. RESULTS: Physicians suspected TB in the first 2 hospital days in 66% of these patients in 1987, a rate that increased steadily to 74% in 1990. However, the extent to which physicians considered TB among female patients decreased from 76% to 71% over the 4 years. Controlling for confounding variables by multiple logistic regression, the odds that TB would be suspected early increased 1.8-fold among men (odds ratio [OR], 1.8; 95% confidence interval [CI95], 1.4-2.4), but not in women (OR, 0.6; CI95, 0.2-1.9). Among the five cities, the odds of early suspicion of TB increased most in New York City (OR, 3.9; CI95, 2.0-7.9). CONCLUSIONS: Physicians considered TB in a timely manner in an increasing majority of male, but not female, high-risk patients during the first years of TB resurgence in the United States. Physicians must be aware of the changing epidemiology of HIV and TB, as well as their practice patterns, to prevent nosocomial transmission of this disease.

Acquired Immunodeficiency Syndrome↗