The impact of "early" versus "late" initiation of renal replacement therapy in critical care patients with acute kidney injury: a systematic review and evidence synthesis.

BACKGROUND: The optimal timing of initiating renal replacement therapy (RRT) in critical illness complicated by acute kidney injury (AKI) is not clearly established. Trials completed on this topic have been marked by contradictory findings as well as quality and heterogeneity issues. Our goal was to perform a synthesis of the evidence regarding the impact of "early" versus "late" RRT in critically ill patients with AKI, focusing on the highest-quality research on this topic. METHODS: A literature search using the PubMed and Embase databases was completed to identify studies involving critically ill adult patients with AKI who received hemodialysis according to "early" versus "late"/"standard" criteria. The highest-quality studies were selected for meta-analysis. The primary outcome of interest was mortality at 1 month (composite of 28- and 30-day mortality). Secondary outcomes evaluated included intensive care unit (ICU) and hospital length of stay (LOS). RESULTS: Thirty-six studies (seven randomized controlled trials, ten prospective cohorts, and nineteen retrospective cohorts) were identified for detailed evaluation. Nine studies involving 1042 patients were considered to be of high quality and were included for quantitative analysis. No survival advantage was found with "early" RRT among high-quality studies with an OR of 0.665 (95 % CI 0.384-1.153, p = 0.146). Subgroup analysis by reason for ICU admission (surgical/medical) or definition of "early" (time/biochemical) showed no evidence of survival advantage. No significant differences were observed in ICU or hospital LOS among high-quality studies. CONCLUSIONS: Our conclusion based on this evidence synthesis is that "early" initiation of RRT in critical illness complicated by AKI does not improve patient survival or confer reductions in ICU or hospital LOS.

Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants.

PURPOSE: To evaluate the impact of selenium chemoprevention (200 microg/day) on hospitalizations in HIV-positive individuals. METHOD: Data were obtained from 186 HIV+ men and women participating in a randomized, double-blind, placebo-controlled selenium clinical trial (1998-2000). Supplements were dispensed monthly, and clinical evaluations were conducted every 6 months. Inpatient hospitalizations, hospitalization costs, and rates of hospitalization were determined 2 years before and during the trial. RESULTS: At enrollment, no significant differences in CD4 cell counts or viral burden were observed between the two study arms. Fewer placebo-treated participants were using antiretrovirals (p <.05). The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study. A marked decrease in total admission rates (RR = 0.38; p =.002) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed (p =.01). As a result, the cost for hospitalization decreased 58% in the selenium group, compared to a 30% decrease in the placebo group (p =.001). In the final analyses, selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization (p =.001). CONCLUSION: Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1-infected patients.

Evaluation of HIV prevention and counseling practices of obstetrician/gynecologists in Bogota, Colombia: impact on women's knowledge and risk practices.

The present community-based study in Bogotá, Colombia, investigated risk assessment and preventive counseling practices of obstetrician/gynecologists (ob/gyn n = 34) and their impact on women's (n = 230) knowledge and risk behaviors. The data indicate that physician education has a significant and positive impact on women's knowledge and behavior. After controlling for sociodemographic variables, women instructed by their ob/gyn were 11 times more likely to correctly identify preventive measures (p = 0.0001) and high-risk sexual practices for the HIV /sexually transmitted diseases (STDs) transmission (4x; p = 0.05) and were less likely to engage in high-risk sexual practices (OR = 2; p = 0.05). Few ob/gyns (17%), however, assess risk behaviors and provide risk reduction counseling, and only 6% frequently encouraged HIV testing. These findings highlight the potential public health impact of ob/gyn physicians and underscore the need to increase their involvement in halting the HIV/STD epidemic in Colombia.

"I will miss the study, God bless you all": participation in a nutritional chemoprevention trial.

Randomized controlled clinical trials are often considered to be the "gold standard" for health research. Consequently, understanding the reasons people participate in these trials, especially minority groups who are often under-represented in clinical trials, or populations who have chronic illnesses or abuse drugs, is salient for successful recruitment, retention, and project design. This paper describes the results of a study that was designed to examine some of the ways in which participants in a randomized double blind clinical trial perceived their participation in the clinical trial, and the reasons they gave for continuing in the study. All of the participants were individuals who were using drugs and were infected with the HIV-1 virus, and had participated in a chemoprevention trial. The data from an exit interview were analyzed thematically in order to reveal units of meaning concerning participation and continuation in the clinical trial. The analysis revealed 3 higher-level concepts, or themes, that guided participation: increased health awareness, personal enhancement, and sociability. The data clearly indicated that involvement and retention in the trial were directly related to the ways in which the participants interpreted the study, perceived the benefits they derived from participating, and imbued their participation with value so that it was important and relevant to their own perceptions of health, as well as personal and social well being.

Continued high risk behaviors in HIV infected drug abusers.

To characterize current risk behaviors of HIV drug abusers in the highly active antiretroviral therapy (HAART) era, socio-demographic, medical and behavioral information were obtained and immune measurements determined. High-risk sexual practices were prevalent. Participants diagnosed before 1995 were 6 times more likely to have unprotected sex with HIV+ partners (p = 0.05) and 11 times more likely to use contaminated needles (p = 0.05) than participants with later diagnosis. Consistent condom use was reported by only 7% of the cohort. Many (43%) of the participants reported multiple HIV+ and HIV- concurrent partners. Most (65%), particularly women (OR = 3, p = 0.02), did so for drugs or money. Despite detectable viral loads, 36% reported unprotected anal sex. Antiretroviral-treated men, compared to non-treated, tended to have unprotected anal sex (OR = 2, p = 0.07). The continued high-risk behaviors of HIV drug users, particularly those diagnosed before 1995 and/or on antiretroviral therapy, indicates an urgent need for new public health strategies.

Cholesterol as a Mediator of Alcohol-Induced Risks for Respiratory Disease Hospitalizations among People Living With HIV.

We analyzed the role of cholesterol as a potential mediator of alcohol-increased risk of respiratory infections that required hospitalization in People Living with HIV (PLWH). Using a longitudinal clinic-based design, 346 PLWH were consecutively admitted and followed at Jackson Memorial Medical Center(enrolled in the study). Following national guidelines, PLWH were stratified according to cholesterol levels: <150 mg/dl (Hypocholesterolemia= HypoCHL), 151-200, and >200 mg/dl Hypercholesterolemia =HyperCHL), and compared on the basis of clinical outcomes, lymphocyte phenotypes and behavioral risks. Analyses indicated that compared to HyperCHL participants, HypoCHL subjects were more likely to be hospitalized, particularly for lower respiratory tract infections (LRTI). Excessive admissions were associated with more deviant lymphocyte profiles, particularly limited NK cells. In logistic regression analyses, smoking (OR=1.5), HypoCHL (OR=7.7), and alcohol (OR=1.2) were predictors of LRTI. These findings warrant further investigation of the potential use of HypoCHL as a risk marker, and the cost-effectiveness of switching prevention gears towards HypoCHL, alcohol and tobacco in PLWH.

Low cholesterol? Don't brag yet ... hypocholesterolemia blunts HAART effectiveness: a longitudinal study.

BACKGROUND: In vitro studies suggest that reducing cholesterol inhibits HIV replication. However, this effect may not hold in vivo, where other factors, such as cholesterol's immunomodulatory properties, may interact. METHODS: Fasting blood samples were obtained on 165 people living with HIV at baseline and after 24 weeks on highly active antiretroviral therapy (HAART). Participants were classified as hypocholesterolemic (HypoCHL; <150 mg/dl) or non-HypoCHL (>150 mg/dl) and were compared on viro-immune outcomes. RESULTS: At baseline, participants with HypoCHL (40%) exhibited lower CD4 (197 +/- 181 vs. 295 +/- 191 cells/mm3, p = 0.02) and CD8 (823 +/- 448 vs. 1194 +/- 598 cells/mm3, p = 0.001) counts and were more likely to have detectable viral loads (OR = 3.5, p = 0.01) than non-HypoCHL controls. After HAART, participants with HypoCHL were twice as likely to experience a virological failure >400 copies (95% CI 1-2.6, p = 0.05) and to exhibit <200 CD4 (95% CI 1.03-2.9, p = 0.04) compared with non-HypoCHL. Low thymic output was related to poorer CD4 cell response in HypoCHL subjects. Analyses suggest a dose-response relationship with every increase of 50 mg/dl in cholesterol related to a parallel rise of 50 CD4 cells. CONCLUSIONS: The study implicates, for the first time, HypoCHL with impaired HAART effectiveness, including limited CD4 repletion by the thymus and suboptimal viral clearance.

Interleukin-6 and platelet protagonists in T lymphocyte and virological response.

The present cross-sectional study evaluated the status and relationship of interleukin-6, a platelet growth factor, with platelet counts, viral load, CD4 counts, and antiretroviral treatment in 75 HIV-infected subjects with thrombocytopenia and 50 gender-, race-, age- and antiretroviral treatment-matched controls without thrombocytopenia. Mean IL-6 production was significantly higher in thrombocytopenic participants (13 432+/-8596) than in non-thrombocytopenic subjects (12 859+/-3538 pg/10(5) Lym). Univariate analyses indicated, however, that thrombocytopenic patients were more likely to have <3000 pg of IL-6 than non-thrombocytopenic patients (OR=7 95% CI 1.3-12; P=0.01). For additional analyses, participants were dichotomized above and below 3000 pg of IL-6. Despite similar age, gender, drug use and antiretroviral treatment, thrombocytopenic participants had lower CD4 counts (186.5+/-149 vs. 401+/-286, P=0.005) than non-thrombocytopenic subjects. Thrombocytopenic participants with elevated IL-6, with or without HAART, were more likely to have higher HIV-replication (496 273+/-210 416; 34 656+/-25 332) than thrombocytopenic individuals with low IL-6 levels (105 332+/-42 699; 19 015+/-14 296 P=0.05). Non-thrombocytopenic patients with high IL-6 levels exhibited the highest CD4s (466.7+/-333) and the lowest viral burden (63 094+/-53 300) of the groups. Two distinct categories of HIV-associated thrombocytopenia exist: one accompanied by low IL-6, and another with compensatory elevations of IL-6. In thrombocytopenic individuals, the latter was associated with the poorest immunological and virological responses.

HIV knowledge and risk behaviors among women in law enforcement in Bogota, Colombia: potential role as community educators.

As HIV infection is increasing among women, evaluation, prevention, and education campaigns need to target this vulnerable population. Because of their frequent and accepted contact with members of the community, female law officers, if knowledgeable, could be well suited to provide information/education related to HIV/STD transmission. A survey of HIV/AIDS knowledge and risk behaviors was administered to 120 law enforcement women (LEW) and 60 women from the general population (GPW) in Bogotá, Colombia. LEW indicated a very high (90%) understanding of basic HIV knowledge. Although most (52%) of the LEW did not report high-risk behaviors, 29% indicated having unprotected sex during menses, and 17% had unprotected anal sex. This contrasts, however, with GPW, who were of similar age, but had a significantly higher prevalence (73%) of risky behaviors (P=.004). Moreover, 52% of the GPW reported having unprotected anal sex, and approximately half of this group (55%) indicated having unprotected sex during menses. Alcohol and drug users were also more prevalent in the GPW: 14% frequently used alcohol and 3% inhaled drugs during sexual encounters, contrasted to 2% of LEW reporting alcohol use. GPW were four times more likely than LEW, to engage in high-risk sexual practices [95% confidence interval (CI)=1.9-10.4, P=0.034]. Multivariate analyses indicated that alcohol and/or drug use were significantly associated with high-risk sexual practices [odds ratio (OR)=4.7, 95% confidence intervals (CI)=1.3-18.4, P=.02). Improved educational HIV/AIDS programs are needed, particularly for women in the general population, who use alcohol/drugs during sexual encounters, which account, at least in part, for their high-risk behaviors. Women in law enforcement, who appear knowledgeable and exhibit safer behaviors, could be useful educators for GPW. Because of their professional role in the community, training for LEW in HIV/AIDS education/prevention programs should be considered.

HIV treatment in drug abusers: impact of alcohol use.

Studies of alcohol use in HIV-1 infected patients have resulted in conflicting and limited information regarding prevalence, as well as impact on HIV replication, disease progression and response to antiretroviral therapy. Alcohol, drug abuse and past medical information, including antiretroviral treatment, were obtained using research questionnaires and medical chart review in 220 HIV-1 infected drug users. A physical examination was conducted and blood was drawn to evaluate immune measures and nutritional status. Heavy alcohol consumption, defined as daily or 3 - 4 times per/week, was reported in 63% of the cohort. Men (odds ratio (OR) = 2.6, 95% CI 1.13 - 5.99, p = 0.013), and participants between 35 and 45 years of age were three times more likely to be heavy alcohol users (p = 0.006 and 0.0009, respectively). Low serum albumin levels were more evident in heavy alcohol users than non-drinkers (p = 0.003). Heavy alcohol users receiving antiretroviral therapy were twice as likely to have CD4 counts below 500 than light or non-drinkers (95% CI, 1 - 5.5, p = 0.03), and highly active antiretroviral therapy (HAART)-treated heavy alcohol users were four times less likely to achieve a positive virological response (95% CI, 1.2 - 17, p = 0.04). Alcohol consumption is prevalent in our HIV-1 infected drug user cohort and significantly impacts both immunological and virological response to HAART treatment.

Impact of tobacco use on the development of opportunistic respiratory infections in HIV seropositive patients on antiretroviral therapy.

The increased risk of developing lung diseases in cigarette smokers has been well recognized. The association between smoking and the risk of developing pulmonary infections in HIV-1-infected patients, however, which has not been established, was evaluated in the present study. Twenty-seven cases with lower respiratory infections (15 Pneumocystis carinii pneumonia (PCP), 12 TB cases) were compared with 27 age, gender, socio-economic and HIV status-matched patients, without history of respiratory diseases. Medical history and physical examinations were obtained every 6 months. Blood was drawn for CD4 and viral load measurements. A substantial number of HIV + smokers who developed PCP (one-third) had been on highly active retroviral therapy (HAART) for more than 6 months and prophylaxis had been discontinued. Multivariate analyses indicated that in HIV-infected people, after controlling for HIV status and antiretrovirals, cigarette smoking doubled the risk for developing PCP (p = 0.01). Multivariate analyses demonstrated that long-term smoking also increased the risk (2 x) of developing tuberculosis (p = 0.04). Moreover, daily tobacco use seemed to attenuate by 40% the immune and virological response to antiretroviral therapies. These findings indicate that tobacco use significantly increases the risk of pulmonary diseases in HIV infected subjects and has a potential deleterious impact on antiretroviral treatment.

Psychological burden in the era of HAART: impact of selenium therapy.

OBJECTIVE: To determine the impact of nutritional (selenium) chemoprevention on levels of psychological burden (anxiety, depression, and mood state) in HIV/AIDS. METHOD: A randomized, double-blind, placebo-controlled selenium therapy (200 microg/day) trial was conducted in HIV+ drug users from 1998-2000. Psychosocial measures (STAI-State and Trait anxiety, BDI-depression, and POMS- mood state), clinical status (CD4 cell count, viral load), and plasma selenium levels were determined at baseline and compared with measurements obtained at the 12-month evaluation in 63 participants (32 men, 31 women). RESULTS: The majority of the study participants reported elevated levels of both State (68%) and Trait (70%) anxiety. Approximately 25% reported overall mood distress (POMS > 60) and moderate depression (BDI > 20). Psychological burden was not influenced by current drug use, antiretroviral treatment, or viral load. At the 12-month evaluation, participants who received selenium reported increased vigor (p = 0.004) and had less anxiety (State, p = 0.05 and Trait, p = 0.02), compared to the placebo-treated individuals. No apparent selenium-related affect on depression or distress was observed. The risk for state anxiety was almost four times higher, and nearly nine times greater for trait anxiety in the placebo-treated group, controlling for antiretroviral therapy, CD4 cell decline (> 50 cells) and years of education. CONCLUSIONS: Selenium therapy may be a beneficial treatment to decrease anxiety in HIV+ drug users who exhibit a high prevalence of psychological burden.

Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy.

The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV-1-infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV-1-seropositive drug users was investigated over a 2-year period (1999-2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm 3, malnutrition, and selenium levels of