Role of individual and developmental differences in voluntary cocaine intake in rats.

RATIONALE: Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addiction-like behavior and to examine factors that promote self-administration. METHODS: We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task. RESULTS: Adolescent animals initially sought more cocaine than adults. However, as the adolescents matured, their intake fell and they did not differ from adults in terms of unreinforced lever-pressing, extinction or reinstatement behavior. For both age groups, self-administration was positively correlated with the locomotor response to novelty, the locomotor response to cocaine, and with time in light in the light-dark task. The rats that were insensitive to cocaine's locomotor effects and that spent the least time in light in the light-dark task sought the least cocaine, appearing to be "protected" from the reinforcing effects of cocaine. There was no difference between the two age groups in appearance of this "protected" phenotype. CONCLUSIONS: These results suggest that early onset of drug taking may promote increased use, but does not promote progression to addiction-like behavior. Furthermore, protective factors, such as innate anxiety and insensitivity to cocaine's pharmacological effects, function across developmental stages.

Relation of lifetime trauma and depressive symptoms to mortality in HIV.

OBJECTIVE: In an era of highly active antiretroviral therapies, the authors needed to confirm previous findings showing that stress and depression have an impact on HIV disease progression. The goal of the current study was to examine the effects of lifetime trauma, recent stressful events, and depression on all-cause and AIDS-related mortality among HIV-infected men and women. The authors hypothesized that these psychosocial variables would predict significantly faster HIV-specific and all-cause mortality. METHOD: The authors consecutively sampled HIV-infected men and women who received care at one of eight infectious diseases clinics in five Southeastern states. The sample included 490 patients who were followed by interview for 27 months and followed with their medical records for up to 41 months. RESULTS: There were 29 deaths; 16 were AIDS-related. More lifetime trauma and antigenic marker on helper/inducer T cells (CD4)<200 significantly predicted faster all-cause and AIDS-related mortality. For those at or above the median in trauma, the all-cause death rate was 3.54 per 100 person-years, compared to 1.72 for those below the median. For those at or above the median in trauma, the AIDS-related death rate was 2.13 per 100 person-years, compared to 0.77 for those below the median. Depressive symptoms and higher baseline viral load were significantly related to greater risk of AIDS-related mortality. CONCLUSIONS: Further research is needed to determine if interventions to address trauma and depression can modify these detrimental effects on HIV.

Minorities, the poor, and survivors of abuse: HIV-infected patients in the US deep South.

BACKGROUND: The HIV/AIDS epidemic in the U.S. South is undergoing a marked shift toward a greater proportion of new HIV/AIDS cases in women, African-Americans, and through heterosexual transmission. METHODS: Using consecutive sampling, 611 participants were interviewed from eight Infectious Diseases clinics in five southeastern states in 2001 to 2002. RESULTS: Sixty four percent of participants were African-American, 31% were female, and 43% acquired HIV through heterosexual sex; 25% had private health insurance. Eighty-one percent were on antiretroviral therapy, and 46% had HIV RNA viral loads (VL) <400. Women and racial/ethnic minorities were less likely to be on antiretrovirals and to have VL <400. Probable psychiatric disorders (54%) and history of childhood sexual (30%) and physical abuse (21%) were common. CONCLUSIONS: Prevention and care systems need to address the HIV epidemic's shift into poor, minority, and female populations. High levels of trauma and probable psychiatric disorders indicate a need to assess for and address these conditions in HIV clinical care.

Predictors of AIDS-related morbidity and mortality in a southern U.S. Cohort.

Advances in the treatment of HIV and associated opportunistic infections (OIs) have led to dramatic reductions in HIV-related morbidity and mortality in the United States, but not all patients have benefited equally. A longitudinal analysis of the Coping with HIV/AIDS in the Southeast (CHASE) cohort evaluated sociodemographic, psychosocial, and clinical factors associated with HIV-related events (incident category C OI or AIDS-related death) among southern HIV-infected patients engaged in clinical care. Participants were followed for a median of 30 months (interquartile range, 17-34 months) after study enrollment (enrollment period December 2001 to April 2002). Ten percent of study participants (50/489) experienced an HIV-related event (incident category C OI and/or AIDS-related deaths) during study follow-up. The rate of HIV-related events was 4.8 per 100 patient-years of observation, and the rate of AIDS-related death was 1.5 per 100 patient-years of observation. In unadjusted survival analyses, younger age, lacking private health insurance, psychosocial trauma, depressive symptoms, lower baseline CD4 count, and less time on antiretroviral therapy during follow-up were associated with HIV-related events. In Cox proportional hazards analysis adjusting for covariates, patients who had suffered more psychosocial trauma (hazard ratio [HR] = 1.97, p = 0.04), who had lower baseline CD4 counts (HR = 0.48 per 100 cells/mm(3), p < 0.01), and who spent less time on antiretroviral therapy during follow-up (HR = 0.47, p = 0.02) were more likely to experience an HIV-related event.

Barriers to antiretroviral adherence: the importance of depression, abuse, and other traumatic events.

Among HIV-infected persons, high-level adherence to antiretroviral medications (>90%-95%) is associated with improved immunologic, virologic, and clinical outcomes, and is necessary to prevent the emergence of viral resistance. This study examines whether lifetime traumatic events including physical and sexual abuse, are associated with antiretroviral nonadherence. We present a cross-sectional analysis of the Coping with HIV/AIDS in the Southeast (CHASE) Study, analyzing data from the enrollment interview and medical records of study subjects. The CHASE Study is a prospective cohort study of consecutively sampled HIV-infected subjects from infectious diseases clinics in five southern states; Alabama, Georgia, Louisiana, North Carolina, and South Carolina. Four hundred seventy-four (78%) of the 611 CHASE study subjects reported being treated with antiretroviral medications at enrollment and are included in this analysis. Nonadherence was defined as the patient's self-report of missing any doses of their antiretroviral medications over the previous 7 days. Among study subjects, 54% reported a history of physical and/or sexual abuse, 91% reported at least one lifetime traumatic event, and 24% reported nonadherence with their antiretrovirals. In multivariable logistic regression analysis, the number of categories of lifetime traumatic events (p = 0.03), the Addiction Severity Index (ASI) alcohol score (p = 0.02), and being uninsured (p = 0.04) were associated with antiretroviral nonadherence. The finding that lifetime traumatic events are associated with antiretroviral nonadherence, particularly among those who have been traumatized in multiple ways, highlights the complex and often persisting manifestations of such trauma and calls for further investigation.

Prevalence of childhood sexual abuse and physical trauma in an HIV-positive sample from the deep south.

We examined prevalence and predictors of trauma among HIV-infected persons in the Deep South using data from the Coping with HIV/AIDS in the Southeast (CHASE) study. Over 50% of CHASE participants were abused during their lives, with approximately 30% experiencing abuse before age 13, regardless of gender. Caregiver characteristics were associated with childhood abuse. Abuse is related to increases in high-HIV-risk activities. The findings help explain why people engage in such high-risk activities and can provide guidance in designing improved care and prevention messages.

Exploring lack of trust in care providers and the government as a barrier to health service use.

OBJECTIVES: We examined associations between trust of health care providers and the government and health service use and outcomes. METHODS: Interviews with a sample of 611 HIV-positive individuals included an attitudinal assessment measuring beliefs concerning the creation of AIDS, information being withheld about the disease, and trust of care providers. RESULTS: Trust in care providers was associated with increased HIV-related out-patient clinic visits, fewer emergency room visits, increased use of antiretroviral medications, and improved reported physical and mental health. Trusting the government was associated with fewer emergency room visits and better mental and physical health. More than one quarter of the respondents believed that the government created AIDS to kill minorities, and more than half believed that a significant amount of information about AIDS is withheld from the public. Ten percent did not trust their provider to give them the best care possible. CONCLUSIONS: Distrust may be a barrier to service use and therefore to optimal health. Distrust is not isolated in minority communities but also exists among members of nonminority communities and equally interferes with their use of services and health outcomes.

How trauma, recent stressful events, and PTSD affect functional health status and health utilization in HIV-infected patients in the south.

OBJECTIVE: In addition to biological markers of human immunodeficiency virus (HIV) disease progression, physical functioning, and utilization of health care may also be important indicators of health status in HIV-infected patients. There is insufficient understanding of the psychosocial predictors of health-related physical functioning and use of health services among those with this chronic disease. Therefore, the current study examines how trauma, severe stressful events, posttraumatic stress disorder (PTSD), and depressive symptoms are related to physical functioning and health utilization in HIV-infected men and women living in rural areas of the South. METHODS: We consecutively sampled patients from 8 rural HIV clinics in 5 southern states, obtaining 611 completed interviews. RESULTS: We found that patients with more lifetime trauma, stressful events, and PTSD symptoms reported more bodily pain, and poorer physical, role, and cognitive functioning. Trauma, recent stressful events, and PTSD explained from 12% to 27% of the variance in health-related functioning, over and above that explained by demographic variables. In addition, patients with more trauma, including sexual and physical abuse, and PTSD symptoms were at greater risk for having bed disability, an overnight hospitalization, an emergency room visit, and four or more HIV outpatient clinic visits in the previous 9 months. Patients with a history of abuse had about twice the risk of spending 5 or more days in bed, having an overnight hospital stay, and visiting the emergency room, compared with those without abuse. The effects of trauma and stress were not explained by CD4 lymphocyte count or HIV viral load; however, these effects appear to be largely accounted for by increases in current PTSD symptoms. CONCLUSION: These findings highlight the importance of addressing past trauma, stress, and current PTSD within clinical HIV care.

Bridging the gap between statistical analysis and decision making in public health research.

Statisticians have eagerly taken on the role of presenting statistical summaries of quantitative data. In areas of health, this means providing point and interval estimates for quantities of interest such as diagnostic risks and treatment effects or providing curve estimates for quantities of interest such as survival probabilities across time. Methods for providing such summaries are highly formalized and constantly evolving. While decision making is the incentive for nearly all such efforts, the process that transforms statistical summaries into decisions usually remains informal and ad hoc. Statisticians have not eagerly accepted the role of promoting formalized decision-theoretic techniques. This paper will argue that the gap between statistical synthesis and decision making is an unnatural and undesirable one, because it undermines the impact of quantitative information. An argument for bridging the gap by expanding the role of statisticians will be presented.