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.

The use of a bronchial blocker to rescue an ill-fitting double-lumen endotracheal tube.

IMPLICATIONS: Using certain specialized endotracheal tubes designed to allow single-lung ventilation for certain thoracic surgical procedures may be fraught with technical difficulties owing to common anatomic anomalies. This case report describes a simple solution for an ill-fitting right double-lumen endotracheal tube using a balloon-tipped catheter.

Clinical and socioeconomic determinants of health care use among HIV-infected patients in the Department of Veterans Affairs.

This study estimates the impact of clinical and socioeconomic characteristics on health care use for HIV-infected patients. Data come from the Department of Veterans Affairs (VA) HIV Registry, which electronically extracts data from patients' automated medical records, and from patient interviews. Unlike prior studies, this analysis includes a staging system incorporating CD4 count and AIDS-defining diagnoses. Results showed that clinical factors were the most important determinants of health care use; socioeconomic variables were seldom significant. These findings were expected, since the VA is an equal access system, providing care regardless of socioeconomic status.

Anesthetic considerations for patients with severe emphysematous lung disease.

The pathophysiology, medical and surgical management of emphysema have been reviewed as a foundation to the physiological goals and principles of anesthetic management of patients with emphysema. An understanding of the cardiovascular and respiratory consequences of emphysema combined with anesthesia, PPV, and thoracic surgery is essential to achieving the challenging physiological goals of providing anesthesia, positive pressure and one-lung ventilation, and postoperative analgesia in a manner consistent with rapid postoperative extubation, hemodynamic stability, adequate gas exchange, and minimal barotrauma for this population of patients.

Two- to three-year follow-up of patients with single-vessel coronary artery disease randomized to PTCA or medical therapy (results of a VA cooperative study). Veterans Affairs Cooperative Studies Program ACME Investigators. Angioplasty Compared to Medicine.

Despite increasing use of percutaneous transluminal coronary angioplasty (PTCA) to treat stenotic coronary artery disease, there are relatively few prospective studies evaluating its long-term effectiveness. We prospectively randomized 212 stable patients with provocable myocardial ischemia and single-vessel subocclusive coronary disease to receive primary therapy with either PTCA or medical therapy. This report presents the clinical follow-up of these patients at a mean, after randomization, of 2.4 years for interview and 3.0 years for exercise testing. Of the 212 patients originally randomized, 175 received an extended follow-up interview, and 132 underwent exercise testing; 62% of patients in the PTCA group were angina free compared with 47% of patients in the medical group (p <0.05). Furthermore, exercise duration as measured by treadmill testing was prolonged by 1.33 minutes over baseline in the PTCA group, whereas it decreased by 0.28 minutes in the medical group (p <0.04). Although the angina-free time on the treadmill was not different (p=0.50), fewer patients in the medical group developed angina on the treadmill at 3 years than those in the PTCA group (p=0.04). By 36 months, excluding the initial randomized PTCA, use of PTCA and use of coronary artery bypass surgery were not different in the 2 treatment groups. These data indicate that some of the early benefits derived from PTCA in patients with single-vessel coronary artery disease are sustained, making it an attractive therapeutic option for these patients.

Manufacture and measurement of nitrogen oxides.

A decade of research has identified nitric oxide as a unique endogenous biologic mediator with functions as diverse as vasodilation, macrophage cytotoxicity, platelet adhesion, and memory formation. Measurement devices, previously used in research on atmospheric nitrogen oxides, are being adapted for and applied to clinical situations without approval, regulation, or rigorous testing, and with little understanding of how the devices work or their limitations. This article discusses the chemistry, manufacture, and measurement of nitrogen oxides.

Predicting outcomes in HIV-infected veterans: I. Progression to AIDS.

This article and the following article (Parts I and II) report the development of two clinical staging systems for HIV-infected individuals. The objective of the research reported here (Part I) was to construct a clinical staging system to predict progression to AIDS. We analyzed data from VA Cooperative Study Number 298, a multicenter, double-blind, randomized trial that compared immediate versus deferred zidovudine therapy in 338 HIV-infected individuals who did not have AIDS at enrollment. Baseline variables were tested in univariate Cox regression for their relationship to progression to AIDS, and those that appeared predictive were examined in multivariable analysis. Based on these analyses, we constructed a new clinical staging system based on CD4+ cell count, age, hemoglobin, oral hairy leukoplakia or oral thrush, and fever. The stages of the system were significant predictors of progression to AIDS (p = 0.0001, log-rank test). In conclusion, simple, valid, clinical staging systems for HIV-infected patients can be constructed using information that is readily available in clinical practice settings. Such systems provide better prognostic distinction than CD4+ cell count alone by taking into account the known prognostic effects of other variables.

Predicting outcomes in HIV-infected veterans: II. Survival after AIDS.

This article (Part II) and the preceding article (Part I) report the development of two clinical staging systems for HIV-infected individuals. The objective of the research reported here (Part II) was to construct a clinical staging system to predict survival in patients with AIDS. We analyzed data from VA Cooperative Study Number 298, a multicenter, double-blind, randomized trial that compared immediate versus deferred zidovudine therapy in HIV-infected individuals. Baseline variables obtained at the onset of AIDS in 204 individuals were tested in univariate Cox regression for their relationship to survival, and those that appeared predictive were examined in multivariable analysis. Based on these analyses, we constructed a new AIDS Clinical Staging System. The system is based on age, CD4+ cell count, type of first AIDS-defining condition, and functional status. The stages of the system were significant predictors of survival (p = 0.0001, log-rank test). In conclusion, valid, simple clinical staging systems for patients with AIDS can be developed based on a few variables that are readily available in clinical settings.

Evaluation of exercise thallium scintigraphy versus exercise electrocardiography in predicting survival outcomes and morbid cardiac events in patients with single- and double-vessel disease. Findings from the Angioplasty Compared to Medicine (ACME) Study.

OBJECTIVES: We sought to evaluate the prognostic ability of cardiac exercise stress tests in predicting cardiac mortality and morbidity in a low risk group of patients with established coronary artery disease (CAD). BACKGROUND: Although previous studies have demonstrated the superior value of stress nuclear cardiac scintigraphy in the prognosis of patients with CAD, none of these studies have focused on patients with a proven angiographic low risk profile (i.e., single- and double-vessel CAD). METHODS: Three hundred twenty-eight patients with documented single- and double-vessel disease were treated by random assignment to percutaneous transluminal coronary angioplasty or medical therapy in the Angioplasty Compared to Medicine (ACME) trial. Six months after randomization, maximal symptom-limited exercise tests were performed with electrocardiography (n = 300) and thallium scintigraphy (n = 270). Patients were followed up for a minimum of 5 years thereafter. RESULTS: A reversible thallium perfusion deficit documented after 6 months of either therapy was associated with an adverse mortality outcome (18% mortality rate with a reversible thallium perfusion defect and 8% mortality rate with no reversible thallium perfusion deficit, p = 0.02). Moreover, an important mortality gradient was demonstrated in relation to the number of reperfusing defects (0 = 7%, 1 to 2 = 15%, >3 = 20%, p = 0.04). Exercise electrocardiography did not predict this mortality outcome. CONCLUSIONS: A reversible thallium perfusion deficit demonstrated 6 months after medical therapy or coronary angioplasty is a valuable prognostic marker in patients with angiographically documented single- and double-vessel disease and is superior to exercise electrocardiography in this regard.

Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis. Veterans Affairs Cooperative Variceal Sclerotherapy Group.

BACKGROUND: Male alcoholics hospitalized with actively bleeding esophageal varices were treated with sclerotherapy or sham sclerotherapy and the outcomes during the index hospitalization were compared. METHODS: The 87 patients were a subset of 253 patients enrolled in a prospective, randomized, single-blind, multicenter, controlled trial conducted in 12 VA medical centers. The patients (44 sclerotherapy, 43 sham therapy) were actively bleeding from esophageal varices at either randomization endoscopy (49) or follow-up endoscopy (38). Events and resource use during the index hospitalization were recorded. RESULTS: In 40 (91%) of the sclerotherapy and 26 (60%) of the sham therapy patients, bleeding was stopped during the endoscopy session (p < 0.001). During the hospitalization, 10 (25%) sclerotherapy and 21 (49%) sham therapy patients died (p = 0.04, relative risk 2.17, 95% CI [1.02, 4.61]); 9 sclerotherapy and 22 sham therapy patients rebled (p = 0.005). The median transfusion requirement was higher for sham therapy (8 vs 4 units, p = 0.001), the number of median ICU hours was greater (101 vs 55, p < 0.001), and more patients in this group required shunt surgery (6 vs 0, p = 0.01). CONCLUSION: Sclerotherapy, compared to no sclerotherapy, stops hemorrhage from actively bleeding esophageal varices and reduces use of resources. Sclerotherapy significantly increased hospital survival.

Changes in plasma HIV RNA levels and CD4+ lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure. VA Cooperative Study Group on AIDS.

BACKGROUND: Markers are needed for assessing response to antiretroviral therapy over time. The CD4+ lymphocyte count is one such surrogate, but it is relatively weak. OBJECTIVE: To assess the association of changes in plasma human immunodeficiency virus (HIV) RNA level and CD4+ lymphocyte count with progression to the acquired immunodeficiency syndrome (AIDS). DESIGN: Analysis of data from a subset of patients in a multicenter, randomized, clinical trial. SETTING: Six Veterans Affairs medical centers and one U.S. Army medical center. PATIENTS: 270 symptomatic HIV-infected patients from the Veterans Affairs Cooperative Study on AIDS. INTERVENTION: Patients were randomly assigned to receive zidovudine or placebo initially; a cross-over protocol was established for patients receiving placebo who had disease progression. MEASUREMENTS: Reverse transcriptase polymerase chain reaction on cryopreserved plasma samples, previously obtained CD4+ lymphocyte counts, and clinical events. RESULTS: For each decrease of 0.5 log10 copies/mL in plasma HIV RNA level, averaged over the 6 months after randomization, the relative risk (RR) for progression to AIDS was 0.67 (P < 0.001). In a subset of 70 treated patients with long-term follow-up, a return to baseline plasma HIV RNA levels within 6 months of randomization was associated with progression to AIDS (RR, 4.28; P = 0.004). Plasma HIV RNA levels or CD4+ lymphocyte counts over time were more strongly associated with progression to AIDS than were baseline levels or counts. CONCLUSIONS: An adequate virologic response after initiation of antiretroviral therapy seems to require a decrease in plasma HIV RNA level of at least 0.5 log10 copies/mL that is sustained for at least 6 months. The independent relation between plasma HIV RNA level and CD4+ lymphocyte count over time and clinical outcome suggests that the measurement of plasma HIV RNA level, in addition to the CD4+ lymphocyte count, has a role in guiding the management of antiretroviral therapy.

Percutaneous transluminal coronary angioplasty versus medical therapy for stable angina pectoris: outcomes for patients with double-vessel versus single-vessel coronary artery disease in a Veterans Affairs Cooperative randomized trial. Veterans Affairs ACME InvestigatorS.

OBJECTIVES: This study sought to assess outcomes of men with double-vessel coronary artery disease randomly assigned to treatment by percutaneous transluminal coronary angioplasty (PTCA) or medical therapy, compared with previously reported outcomes for men with single-vessel disease. BACKGROUND: We previously reported that PTCA provides better symptom relief and treadmill performance than medical therapy for men with stable angina pectoris due to single-vessel disease. Whether this advantage applies to patients with double-vessel disease is unknown. METHODS: Male patients (n = 328) with stable angina pectoris and ischemia on treadmill testing were randomly assigned to PTCA or medical therapy; 101 patients had double-vessel disease, and 227 had single-vessel disease. Symptoms, treadmill performance, quality of life score, coronary stenosis and myocardial perfusion were compared at baseline and at 6 months. Patients were followed up for up to 6 years and underwent additional treadmill testing 2 to 3 years after randomization. RESULTS: PTCA-treated and medically treated patients with double-vessel disease experienced comparable improvement in exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with baseline. This contrasts with greater advantages favoring PTCA by these criteria in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6 months persisted at late follow-up. Patients undergoing double-vessel dilation had less complete initial revascularization (45% vs. 83%) and greater average stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with double-vessel disease showed less improved myocardial perfusion imaging (59% vs. 75%). CONCLUSIONS: PTCA is beneficial in male patients with double-vessel disease; however, we cannot demonstrate the same advantage over medical therapy seen in similar patients with single-vessel disease. Less complete revascularization and greater restenosis for patients having multiple dilations would account for these findings. Alternatively, a type 2 error might be operative. Technical advances since completion of this trial might improve these outcomes. These findings warrant further investigation in a larger trial.

Predicting progression to AIDS. An evaluation of two approaches.

This study evaluated the predictive validity of two clinical staging systems for HIV infection (the Rabeneck and Royce systems) using data obtained from the Department of Veterans Affairs Cooperative Study Number 298, a randomized clinical trial involving 335 symptomatic patients with CD4 counts of 200 to 500/mm3. The relation between the HIV clinical stages and progression to AIDS was examined using Kaplan-Meier estimates, and Cox models were used to determine if the stages remained predictive after controlling for CD4 count. Both systems were significant independent predictors of progression to AIDS. This work demonstrates that simple, valid staging systems for HIV infection can be developed that provide greater prognostic distinction than the CD4 count alone.

Importance of cerebrovascular disease in studies of myocardial infarction.

BACKGROUND AND PURPOSE: Myocardial infarction and stroke are both predominantly manifestations of atherosclerosis, yet stroke is commonly ignored in prognostic studies and therapeutic trials of ischemic heart disease. Our objective was to assess, in a community setting, the relative importance of stroke among patients at high risk for myocardial infarction. METHODS: We analyzed 1985 survey data from the National Academy of Science Twin Registry of white male veterans. To minimize confounding by genetic and environmental factors, we restricted our analysis to the rates of stroke and myocardial infarction among monozygotic twins counted as individuals or as twin pairs. RESULTS: Among 2764 monozygotic twins aged 58 to 68 years, the overall rate of myocardial infarction was 10% and stroke 3.1%. Among 2632 individual monozygotic twins (95%) with complete responses, the rate of stroke among men with a history of myocardial infarction was 7.5% (17/228) compared with 2.4% (58/2404) among those without myocardial infarction (odds ratio = 3.3, chi square 2 = 19.1, P<.001). A strong association between stroke and myocardial infarction was also found when the data were analyzed for twin pairs (chi square 2 = 135, P<.0005). CONCLUSIONS: Our results suggest that stroke, in addition to myocardial infarction, should be considered as an outcome in clinical investigations of ischemic heart disease.

Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.

BACKGROUND: Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. METHODS: We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma. RESULTS: Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS: Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well.

Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment.

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).

Nitric oxide: delivery, measurement, and clinical application.

The biologic and therapeutic roles of NO are rapidly being elucidated. Before inhalational NO administration is commonplace, there is a clear need for consensus regarding safe and accurate delivery and measurement systems. The potential for NO usage appears large and potentially life-saving; yet multicenter trials need to carefully evaluate efficacy and safety.

Delayed-type hypersensitivity skin tests are an independent predictor of human immunodeficiency virus disease progression. Department of Veterans Affairs Cooperative Study Group.

Delayed-type hypersensitivity (DTH) testing was evaluated as a predictor of human immunodeficiency virus (HIV) disease progression in 336 symptomatic patients with baseline CD4 cell counts of 200-500/mm3 who were participating in a randomized trial of early versus late therapy with zidovudine. Patients with a response of > 2 mm to any of seven antigens were categorized as reactive; those without were anergic. Anergic patients were significantly more likely than reactive patients to have HIV disease progression as evidenced by decrease in CD4 cell count (52% vs. 27%), development of AIDS (33% vs. 17%), or death (18% vs. 9%) (P < or = .02), irrespective of time of zidovudine initiation. By multivariate analysis, DTH results were an independent predictor of HIV progression separate from CD4 cell count, p24 antigen positivity, or level of beta 2-microglobulin. DTH skin tests are an independent predictor of HIV disease progression and may be of value in the evaluation of a patient's immune status.