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Biomedical subjects

H S Sacks

Publications and source records attributed to H S Sacks.

At least 19 recordsLinked to original sources
PubMed2001

Outpatient treatment of deep venous thrombosis in diverse inner-city patients.

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.

Adult↗
PubMed2001

Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial.

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.

AIDS-Related Opportunistic Infections↗
PubMed2001

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy.

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.

Anti-HIV Agents↗
PubMed1999

Tuberculosis preventive therapy for HIV-infected people in sub-Saharan Africa is cost-effective.

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.

AIDS-Related Opportunistic Infections↗
PubMed1999

Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women.

BACKGROUND: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. METHODS: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. RESULTS: Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age < 30 years versus > or = 40 years; OR = 1.75; 95% CI = 1.23-2.49). CONCLUSIONS: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis.

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.

Adult↗
PubMed1997

Predictors and impact of patients lost to follow-up in a long-term randomized trial of immediate versus deferred antiretroviral treatment.

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.

Adult↗
PubMed1997

Hypothalamic-pituitary axis dysfunction in critically ill patients with a low free thyroxine index.

The purpose of this study is to investigate the association of hypothalamic-pituitary axis abnormalities with the free thyroxine index (FTI) in critically ill patients. Fourteen critically ill patients and twenty healthy volunteers were studied using combined anterior pituitary gland testing with CRF, GHRH, TRH, and GnRH. The subjects were grouped as follows: I-healthy volunteers; II-sick/normal FTI; and III-sick/low FTI. Serial measurements of hormones were performed over a two-hour interval and the following parameters were measured: baseline level, response amplitude and time to maximal response. Response velocities and area-under-the-curves (integrated responses) were also computed. Group III had a longer mean ICU duration prior to testing than group II. Urinary cortisol, serum cortisol and serum PRL levels were elevated in groups II and III. However, group III had lower baseline ACTH levels, slower ACTH and TSH response velocities and decreased PRL integrated responses. Cortisol response parameters were similar between groups II and III. There were no differences in LH, FSH or GH response velocities or integrated responses among the 3 groups. These data confirm that critically ill patients develop hyperprolactinemia and hypothalamic-pituitary-adrenal axis activation but when a low FTI exists, a plurality of changes occur reflected by attenuated PRL, TSH and ACTH responses despite unaffected adrenal cortisol output.

Adult↗
PubMed1997

The relationship between study design, results, and reporting of randomized clinical trials of HIV infection.

We examined whether the study design of randomized clinical trials for medications against human immunodeficiency virus (HIV) may affect the results and whether the outcomes of these trials affect reporting and publication. We used a database of 71 published randomized HIV-related drug efficacy trials and considered the following study design factors: endpoint definition and method of analysis, masked design, sample size, and duration of follow-up. Large variation was noted in the methods of analysis for surrogate endpoints. Often statistical significance for a surrogate endpoint was not associated with statistical significance for the clinical endpoint or for survival in the same trial, although disagreements in the direction of the treatment effect for surrogate endpoints and survival within individual trials were uncommon. Open-label design seemed to affect the magnitude of the treatment effect for two treatments. The magnitude of the treatment effect in trials of zidovudine monotherapy was inversely related to their sample size, but this probably reflected the confounding effect of longer duration of follow-up in large trials (with a resulting loss of efficacy) rather than publication bias. There was, however, evidence for potential bias in reporting and publication of HIV-related trials. Meta-analyses of published trials for specific treatments demonstrated a sizable treatment benefit for all the examined medications regardless of whether these medications were officially approved, controversial, or abandoned, raising concerns about either publication bias or unjustifiable rejection of potentially useful medications. Compared with trials published in specialized journals, trials published in journals of wide readership were larger (p = 0.001) and 4.4 times more likely to report "positive" results (p = 0.01). We identified several examples of trials with "negative" results that have remained unpublished for a long time. In conclusion, study design factors may have an impact on the magnitude and significance of the treatment effect in HIV-related trials. Bias in reporting can further affect the information that these studies provide.

Anti-HIV Agents↗
PubMed1997

Cost-effectiveness of cytomegalovirus (CMV) disease prevention in patients with AIDS: oral ganciclovir and CMV polymerase chain reaction testing.

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.

AIDS-Related Opportunistic Infections↗
PubMed1996

A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens.

BACKGROUND: Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their relative efficacy and tolerance are not well understood. METHODS: A meta-analysis overviewed 35 randomized trials comparing different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to-treat. On-treatment data were also analyzed when available. RESULTS: Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens. CONCLUSIONS: Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Predictive value of viral load measurements in asymptomatic untreated HIV-1 infection: a mathematical model.

OBJECTIVE: To model the predictive value of viral load measurements in asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 x 10(6)/l and no prior antiretroviral therapy, when the time of seroconversion and the prior levels of viremia are unknown. DESIGN: A mathematical model was constructed for the changes in HIV RNA load over time based on data from cohorts of HIV-infected patients followed since the time of seroconversion. METHODS: For different values of viral load, the time to progression to AIDS or an equivalent state [progression to AIDS equivalent (PAE)] was calculated using a wide range of estimates for the time since seroconversion and the rate of change of the viral load over time. RESULTS: In the absence of antiretroviral treatment, patients with a viral load of 10(5) copies/ml serum are at risk for PAE in less than 3 years (0-3 years) and patients with a viral load half a log higher are at risk in less than 1 year. In contrast, patients with a viral load of 10(4.5) have at least 1.9 years and may have up to 8 years before risk of PAE. Patients with a viral load of 10(4) RNA copies/ml have at least 2.8 years and may have up to 19 years before risk of PAE. The rate of change of the viral load was an important predictor of outcome; the time since seroconversion had only a minor effect. CONCLUSIONS: The viral load in the plasma or serum has predictive value even if the time of seroconversion is unknown. The rate of change of viral load over time may also be an important predictive factor. Serial measurements of viral load over time may provide therapeutic guidance.

CD4 Lymphocyte Count↗
PubMed1996

Synergy, activity and tolerability of zidovudine and interferon-alpha in patients with symptomatic HIV-1 infection: AIDS Clincal Trial Group 068.

Thirty-four subjects with symptomatic HIV-1 infection, p24 antigenaemia, and CD4 cell counts > 200/mm3 were randomly assigned to receive treatment with either zidovudine (ZDV) orally, interferon-alpha (IFN-alpha) subcutaneously, or both at respective low (200 mg ZDV/ 2 million international units IFN-alpha (MIU)), middle (400 mg/4 MIU) or high (600 mg/6 MIU) daily dose levels for 12 weeks. Thereafter, all patients received combination therapy at the initially assigned dose level to a total of 96 weeks. This design permitted analysis by the combination index (CI) method, which demonstrated antiretroviral synergy between ZDV and IFN-alpha with respect to p24 antigen suppression. Over the first 12 weeks, combination therapy was acceptably tolerated, more so than IFN-alpha monotherapy, and it was significantly more active in suppressing antigenaemia than either of the monotherapies. Similarly, the high-dose combination was the most active dose level over weeks 12 to 96. Combination ZDV/IFN-alpha at the optimal dose level defined by this trial merits further study. In addition, the CI design strategy employed here may be useful for the investigation of new antiretroviral combinations.

Administration, Cutaneous↗
PubMed1995

The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature.

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.

Age Factors↗