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We compared low-dose insulin regimens in a prospective randomized trial in 30 patients with diabetic ketoacidosis. One group received a loading dose of 0.44 U/kg body weight of regular insulin half intramuscularly and half intravenously followed by 7 U/h intramuscularly, whereas the other group received a loading dose of 0.44 U/kg intravenously followed immediately by a constant infusion of 7 U/h in albumin-free saline. The time for metabolic control of the ketoacidosis was not significantly different in the two groups. Five patients in each group developed mild hypokalemia (serum potassium, 3.0 to 3.4 meq/litre). No patient became hypoglycemic, and there were no deaths within the follow-up period (24 h). In the treatment of diabetic ketoacidosis, low doses of insulin administered by the priming dose-intermittent intramuscular route are as effective as the constant infusion method. [ABSTRACT FROM AUTHOR]

Objective: To quantify the protective efficacy of influenza vaccine in elderly persons.Data Sources: A MEDLINE search was done using the index terms influenza vaccine, vaccine efficacy, elderly, mortality, hospitalized, and pneumonia. Appropriate references in the initially selected articles were also reviewed.Study Selection: Only cohort observational studies with mortality assessment were included in the meta-analysis. In addition, 3 recent case-control studies, 2 cost-effectiveness studies, and 1 randomized, double-blind, placebo-controlled trial were reviewed.Data Extraction: Vaccine and epidemic virus strains, age and sex of patients, severity of illness, patient status, and study design were recorded. Upper respiratory illness, hospitalization, pneumonia, and mortality were used as outcome measures.Data Synthesis: In a meta-analysis of 20 cohort studies, the pooled estimates of vaccine efficacy (1-odds ratio) were 56% (95% Cl, 39% to 68%) for preventing respiratory illness, 53% (Cl, 35% to 66%) for preventing pneumonia, 50% (Cl, 28% to 65%) for preventing hospitalization, and 68% (Cl, 56% to 76%) for preventing death. Vaccine efficacy in the case-control studies ranged from 32% to 45% for preventing hospitalization for pneumonia, from 31% to 65% for preventing hospital deaths from pneumonia and influenza, from 43% to 50% for preventing hospital deaths from all respiratory conditions, and from 27% to 30% for preventing deaths from all causes. The randomized, double-blind, placebo-controlled trial showed a 50% or greater reduction in influenza-related illness. Recent cost-effectiveness studies confirm the efficacy of influenza vaccine in reducing influenza-related morbidity and mortality and show that vaccine provides important cost savings per year per vaccinated person.Conclusion: Despite the paucity of randomized trials, many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain. Influenza immunization is an indispensable part of the care of persons 65 years of age and older. Annual vaccine administration requires the attention of all physicians and public health organizations. [ABSTRACT FROM AUTHOR]

Purpose: A meta-analysis of the effect of antihypertensive drug treatment on mortality and morbidity in elderly patients.Data Sources: A literature search of published articles from January 1980 to February 1992.Study Selection: Randomized controlled trials of drug treatment of hypertension with end points for elderly patients reported separately.Data Extraction: Mortality or morbidity end points or both in patients older than 59 years were pooled by determination of typical odds ratio. A meta-regression was used to study heterogeneity.Results: Nine major trials with 15,559 patients older than 59 years were identified. Death rates in the control group varied between 2.7% and 77.2%; stroke and coronary mortality increased with the severity-of-illness rank (P < 0.001). Overall, treated patients had an approximately 12% reduction in all-cause mortality (odds ratio, 0.88; 95% CI, 0.80 to 0.97; 953 events compared with 1069 events, P = 0.009). There was a 36% reduction in stroke mortality (odds ratio, 0.64; CI, 0.49 to 0.82; 94 events compared with 149 events, P < 0.001) and a 25% reduction in coronary heart disease mortality (odds ratio, 0.75; CI, 0.64 to 0.88; 263 events compared with 350 events, P < 0.001). Coronary morbidity was reduced 15% (odds ratio, 0.85; CI, 0.73 to 0.99; 325 events compared with 379 events, P = 0.036), and stroke morbidity was reduced 35% (odds ratio, 0.65; CI, 0.55 to 0.76; 247 events compared with 382 events, P < 0.001).Conclusion: Overall, treatment of hypertension in elderly patients produces a significant benefit in total mortality and cardiovascular morbidity and mortality. However, this benefit may be reduced in the oldest age groups. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients.Design and Subjects: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations.Measurements and Main Results: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal.Conclusions: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant. [ABSTRACT FROM AUTHOR]

Objective: To analyze the policies of isoniazid prophylaxis for human immunodeficiency virus (HIV)-infected tuberculin reactors and for HIV-infected anergic patients with unknown tuberculin status.Methods: Transition-state model of clinical immune deterioration of HIV-infection over ten years, review of published data, and a survey of AIDS experts. Outcome measures are the numbers of tuberculosis cases and deaths prevented and isoniazid toxicity cases and deaths occurring with prophylaxis.Patients: Hypothetical cohorts of HIV-infected 40-year-olds.Results: Because the tuberculosis activation rate is so high in HIV-infected patients, the benefits of prophylaxis far outweigh the risks of isoniazid toxicity for tuberculin reactors with HIV infection at any stage of immune function: 1,469-2,868 tuberculosis cases and 170-274 deaths are prevented per 10,000 cohort over ten years, depending upon the cohort's initial immune state. The benefits of prophylaxis outweigh the risks of isoniazid toxicity for anergic HIV-infected patients if they come from a community with a 2% to 3% or greater prevalence of Mycobacterium tuberculosis infection.Conclusions: Isoniazid prophylaxis is a reasonable prevention measure for HIV-infected tuberculin reactors and for many HIV-infected anergic patients. [ABSTRACT FROM AUTHOR]

Objective: To perform a decision analysis to determine the thresholds of safety and effectiveness that would justify short-term zidovudine (AZT) administration for persons with accidental percutaneous exposure to HIV-positive blood.Design: Published data were used to estimate the seroconversion rate (0.42%), rate of developing AIDS if HIV-infected (5%/year), and survival with AIDS (50%/year). No information is available on zidovudine effectiveness and little is known about fatal toxicity of zidovudine. Death from AIDS or from zidovudine toxicity was used as the endpoint.Results: For those with exposure to blood known to be HIV-seropositive, the benefits of zidovudine outweight the risks if efficacy is above approximately 3% to 8%. Wide variations in the assumptions have little effect on the thresholds.Conclusions: Since clinical trials to determine zidovudine effectiveness in this setting will probably never be done, decision analysis offers the only quantitative method for addressing this question. Unless future studies show zidovudine to be both ineffective and toxic, the benefits of short-term administration of zidovudine outweigh the risks immediately after exposure to HIV-positive blood. Zidovudine benefits do not clearly outweigh the risks after exposure to blood of unknown serologic status, or if there is a delay in starting therapy. [ABSTRACT FROM AUTHOR]

Purpose: We sought to describe the development and outcomes of a hospital-based program designed to provide safe and effective outpatient treatment to a diverse group of patients with acute deep venous thrombosis., Methods: Patients enrolled in the program were usually discharged on the day of or the day after presentation. Low- molecular-weight heparin was administered for a minimum of 5 days and warfarin was given for a minimum of 3 months. The hospital provided low-molecular-weight heparin free of charge to patients. Patients received daily home nursing visits to monitor the prothrombin time, assess compliance, and detect complications. The inpatient and outpatient records of the first 89 consecutive patients enrolled in the program were reviewed. Patients were observed for a 3-month period after enrollment., Results: The median length of stay was 1 day. Low-molecular-weight heparin was administered for a mean (+/- standard deviation [SD]) of 4.7 +/- 2.4 days at home. Recurrent thromboembolism was noted in 1 patient (1%), major bleeding in 2 patients (2%), and minor bleeding in 2 patients (2%). No patients died or developed thrombocytopenia. Assuming that patients would have been hospitalized for the duration of treatment with low-molecular-weight heparin, the program eliminated a mean of 4.7 days of hospitalization, with an estimated reduction of $1,645 in total health care costs per patient., Conclusion: This hospital-based program to provide outpatient treatment of deep venous thrombosis to a diverse group of inner-city patients achieved a low incidence of adverse events and substantial health care cost savings. Specific strategies, including providing low-molecular-weight heparin free of charge and daily home nursing visits, can be utilized to facilitate access to outpatient treatment and ensure high-quality care.

Context: Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs)., Objective: To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients., Design and Setting: Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors)., Patients: A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion)., Main Outcome Measures: Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion., Results: At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels., Conclusions: We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.

To initiate infection, HIV-1 requires a primary receptor, CD4, and a secondary receptor, principally the chemokine receptor CCR5 or CXCR4. Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 transmitted in vivo generally uses CCR5 (R5), but later CXCR4 (X4) strains may emerge; this shift heralds CD4+ cell depletion and clinical deterioration. We asked whether antiretroviral therapy can shift HIV-1 populations back to R5 viruses after X4 strains have emerged, in part because treatment has been successful in slowing disease progression without uniformly suppressing plasma viremia. We analyzed the coreceptor usage of serial primary isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage was determined by using a HOS-CD4+ cell system, biological and molecular cloning, and sequencing the envelope gene V3 region. By constructing a mathematical model to measure the proportion of virus in a specimen using each coreceptor, we demonstrated that the predominant viral population shifted from X4 at baseline to R5 strains after treatment. Multivariate analyses showed that the shift was independent of changes in plasma HIV-1 RNA level and CD4+ cell count. Hence, combination therapy may lead to a change in phenotypic character as well as in the quantity of HIV-1. Shifts in coreceptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs.

Objective: Since antiretroviral therapy is largely unavailable to HIV-infected patients in developing countries and recent clinical trials have shown that tuberculosis (TB) preventive therapy can reduce TB and HIV-associated morbidity and mortality, we studied the effectiveness and cost-effectiveness of TB preventive therapy for HIV-infected persons in sub-Saharan Africa., Methods: A Markov model that used results of clinical trials of TB preventive therapy in sub-Saharan Africa and literature-derived medical care costs was used to evaluate three preventive therapy regimens in HIV-infected, tuberculin-positive patients in Uganda: (1) daily isoniazid (INH) for 6 months, (2) daily INH and rifampin (RIF) for 3 months, and (3) twice-weekly RIF and pyrazinamide (PZA) for 2 months., Results: All three regimens extend life expectancy and reduce the number of TB cases. When only medical care costs are considered, all three preventive therapy regimens cost more than not providing preventive therapy to extend life and prevent active tuberculosis. When medical care and social costs are considered together, 6-months of daily INH treatment will save money relative to no preventive therapy and when the costs associated with treating secondary infections are included, all three preventive therapy regimens are less expensive than no preventive therapy. With the inclusion of secondary infection costs, 6 months of daily INH results in savings of $24.16 per person., Conclusions: TB preventive therapy taken by HIV-infected tuberculin reactors in sub-Saharan Africa results in extended life-expectancy, reduction of the incidence of TB and monetary savings in medical care and social costs. TB control policy in sub-Saharan Africa should include preventive therapy.

Background: The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection., Methods: Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3)., Results: Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean +/- 1 SD BFU-E/10(5) cells plated: normal = 14.1 +/- 7.9, HIV+ = 17.2 +/- 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and didehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean +/- 1 SD for normal cultures = 2.64 +/- 4.15 microM, for HIV+ cultures = 6.28 +/- 10.79 microM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T < or = 10 microM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients., Conclusions: Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.

We studied predictors for losses to follow-up and the impact of such losses in the AIDS Clinical Trials Group 019 protocol, a long-term randomized trial of immediate versus deferred antiretroviral therapy in asymptomatic HIV-1-infected patients with >500 CD4 cells/mm3. The trial was selected because of its key importance in determining guidelines for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patients whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor after adjusting for clinical site. There was large and statistically significant variability in the rates of losses among different clinical sites (p < 0.001). Patient retention was significantly better in clinical sites that enrolled many participants, with 25% of enrollees lost to follow-up in sites enrolling >100 patients and 44% in sites enrolling <33 patients each. As a group, patients lost to follow-up after the 2nd year had steeper declines of CD4 cell counts, and a significantly larger proportion had reached a CD4 cell count <300/mm3 in the year before being lost, compared with patients remaining in the study. Losses to follow-up probably decreased substantially the observed number of primary endpoints, curtailed the power of the trial to demonstrate any difference between immediate and deferred initiation of antiretroviral therapy, and may have introduced large bias in the estimated hazard ratio for the primary endpoint and its statistical significance.

Objective: To perform a cost-effectiveness analysis of strategies to prevent cytomegalovirus (CMV) disease., Method: Markov model and published data., Patients: Hypothetical HIV-infected patients with CD4 cell counts < or = 50 x 10(6)/l and positive CMV serologies., Interventions: Oral ganciclovir daily versus plasma CMV DNA polymerase chain reaction (PCR) testing every 3 months with oral ganciclovir for patients with positive tests., Outcome Measures: The number of CMV disease cases prevented by the interventions, life expectancy, disease-free life expectancy, and the cost to extend life by 1 year., Results: Oral ganciclovir preventive therapy reduces the lifetime number of CMV disease cases by 50 per 1000 cohort, extends life expectancy by 5 days and disease-free life expectancy by 18 days, and costs US$ 1,762,517 per year of life extended. Periodic PCR testing reduces the lifetime number of CMV disease cases by eight per 1000 cohort, extends life expectancy by 1 day and disease-free life expectancy by 3 days, and costs US$ 495,158 per year of life extended. The prevention strategies could be acceptably cost effective only under a combination of optimistic assumptions and reduced costs., Conclusions: Oral ganciclovir preventive therapy and periodic plasma testing for CMV PCR with oral ganciclovir for those with positive tests result in small benefits at great cost. They are not cost-effective prevention strategies for persons with advanced HIV infection and positive CMV serologies.