Instability of tuberculin and Candida skin test reactivity in HIV-infected Ugandans. The Uganda-Case Western Reserve University Research Collaboration

Anergy testing has been used as an adjunct to tuberculin testing for assessing M. tuberculosis (MTB) infection and indications for isoniazid preventive therapy in HIV-infected persons. We examined factors associated with the stability of skin test responses to purified protein derivative (PPD) and candida antigens in a cohort of HIV-infected adults followed prospectively in a tuberculosis preventive therapy trial in Uganda. PPD-positive and anergic subjects in the placebo arms of the preventive therapy study underwent repeat skin testing and immunologic testing including measurement of MTB culture filtrate (CF)-stimulated interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) levels in whole-blood culture supernatants. Anergy was present in 27% of 4,058 HIV-infected subjects screened for the tuberculosis preventive therapy trial compared with 10% of 682 HIV-non-infected persons. On follow-up testing of enrolled subjects, 42% of 139 initially anergic subjects were no longer anergic; two thirds of these had PPD reactions >= 5 mm. Stability of anergy was associated with intercurrent opportunistic infections and AIDS-associated dermatitis at baseline. Thirty-five percent of 313 subjects with an initial positive PPD had a negative PPD test at follow-up, 26% of whom had a positive candida skin test at the same time as the negative PPD test. Baseline MTBCF-stimulated IFN-gamma levels were significantly higher among PPD-positive subjects who remained PPD-positive than in those who were falsely negative. We conclude first that anergy is unstable and second that anergy testing is unreliable in identifying HIV-infected adults who are not infected with MTB and should not be used routinely for this purpose in assessing indications for isoniazid preventive therapy.     

Randomized controlled trial of a preventive intervention for perinatal depression in high-risk Latinas.

Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive–behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual care (UC; n = 105) or an 8-week CBT group intervention during pregnancy and 3 individual booster sessions during postpartum (n = 112). Participants completed measures assessing depressive symptoms (Center for Epidemiological Studies Depression Scale at baseline; Beck Depression Inventory, Second Edition [BDI–II]) and major depressive episodes (Mood Screener) at 5 time points throughout the perinatal period. Results: Intent-to-treat analyses indicated that intervention participants had significantly lower depressive symptoms and fewer cases of moderate depression (BDI–II ≥ 20) at Time 2 than UC participants. These effects were stronger for women who fully participated in the intervention (≥4 classes). The cumulative incidence of major depressive episodes was not significantly different between the intervention (7.8%) and UC (9.6%) groups. Conclusions: A CBT intervention for low-income, high-risk Latinas reduced depressive symptoms during pregnancy but not during the postpartum period. Low levels of depressive symptoms and lower than expected rates of clinical depression in both groups may partially be due to methodological issues. As perinatal depression is a significant public health problem, more work is needed to prevent perinatal depression in low-income, ethnically diverse women. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals.

Objective: To evaluate cognitive-behavioral therapy to enhance medication adherence and reduce depression (CBT-AD) in individuals with HIV. Design: A two arm, randomized, controlled, cross-over trial comparing CBT-AD to enhanced treatment as usual only (ETAU). ETAU, which both groups received, included a single-session intervention for adherence and a letter to the patient's provider documenting her or his continued depression. The intervention group also received 10 to 12 sessions of CBT-AD. Main Outcome Measures: Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems (MEMs) and depression as assessed by blinded structured evaluation. Results: At the acute outcome assessment (3-months), those who received CBT-AD evidenced significantly greater improvements in medication adherence and depression relative to the comparison group. Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes. Treatment gains for those in the intervention group were generally maintained at 6- and 12-month follow-up assessments. By the end of the follow-up period, those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations, though these differences did not emerge before the cross-over, and hence there were not between-groups differences. Conclusions: CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence. Replication and extension in larger efficacy trials are needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isoniazid preventive therapy in human immunodeficiency virus-infected persons. Long-term effect on development of tuberculosis and survival

BACKGROUND: Although the short-term benefit of isoniazid prophylaxis in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis has been shown, long-term benefits are unknown. METHODS: Historical cohort study in an acquired immunodeficiency syndrome unit at a tertiary referral hospital. A sample of 121 HIV-infected patients with positive results on a purified protein derivative test were followed up for development of active tuberculosis and survival. Patients who received isoniazid prophylaxis were compared with patients who did not receive prophylaxis. RESULTS: Of the 121 patients examined, 29 (24%) completed a 9- to 12-month course of isoniazid prophylaxis (median follow-up, 89 months), and 92 (76%) did not receive the drug (median follow-up, 60 months). Active tuberculosis developed in 46 patients (38%). The incidence of tuberculosis was higher among patients with no prophylaxis (9.4 per 100 patient-years) than among patients with isoniazid prophylaxis (1.6 per 100 patient-years) (P = .006). Risk for development of tuberculosis was associated with the absence of isoniazid prophylaxis (relative risk [RR], 6.55; 95% confidence interval [CI], 2.02-21.19). Death during the period of study was more frequent in patients who did not receive isoniazid (50/92 or 54%) than in patients who received isoniazid (7/29 or 24%) (P = .008). Median survival was more than 111 months in patients who received isoniazid compared with 75 months in patients who did not receive isoniazid (P < .001). In a proportional hazards analysis, the development of tuberculosis (RR, 1.88; 95% CI, 1.09-3.27), the absence of isoniazid prophylaxis (RR, 2.68; 95% CI, 1.16-6.17), and a CD4+ cell count lower than 0.20 x 10(9)/L (RR, 3.03; 95% CI, 1.39-6.61) were independently associated with death. Patients who received isoniazid had a longer survival after stratifying for the CD4+ cell count. CONCLUSIONS: Preventive therapy with isoniazid confers long-term protection against tuberculosis and significantly increases survival in patients dually infected with HIV and Mycobacterium tuberculosis.     

Randomized controlled trial of a family cognitive-behavioral preventive intervention for children of depressed parents.

A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9–15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at postintervention (2 months), after completion of 4 monthly booster sessions (6 months), and at 12-month follow-up. Children were assessed by child reports on depressive symptoms, internalizing problems, and externalizing problems; by parent reports on internalizing and externalizing problems; and by child and parent reports on a standardized diagnostic interview. Parent depressive symptoms and parent episodes of major depression also were assessed. Evidence emerged for significant differences favoring the family group intervention on both child and parent outcomes; strongest effects for child outcomes were found at the 12-month assessment with medium effect sizes on most measures. Implications for the prevention of adverse outcomes in children of depressed parents are highlighted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A randomized trial of the effectiveness of cognitive-behavioral therapy and supportive counseling for anxiety symptoms in older adults.

The authors used a randomized trial to compare cognitive-behavioral therapy (CBT) and supportive counseling (SC) in the treatment of anxiety symptoms in older adults who met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria for anxiety disorders. Both conditions had a 6-week baseline no-treatment phase. Treatment was delivered primarily in patients' own homes and in an individual format. Outcomes were assessed at posttreatment and at 3-, 6-, and 12-month follow-ups. There was no spontaneous improvement during the baseline phase. Both groups showed improvement on anxiety measures following treatment, with a better outcome for the CBT group on self-rating of anxiety and depression. Over the follow-up period, the CBT group maintained improvement and had significantly greater improvement than the SC group on anxiety and 1 depression measure. Treatment response for anxiety was also superior for the CBT group, although there was no difference between groups in endstate functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rates of tuberculosis infection in healthcare workers providing services to HIV-infected populations. Terry Beirn Community Programs for Clinical Research on AIDS

OBJECTIVE: To assess the prevalence of tuberculosis (TB) or a positive skin test in healthcare workers (HCWs) providing services to human immunodeficiency virus (HIV)-infected individuals and to determine prospectively the incidence of new infections in this population. DESIGN: This prospective cohort study enrolled 1,014 HCWs working with HIV-infected populations from 10 metropolitan areas. Purified protein derivative (PPD) tuberculin skin tests were placed at baseline and every 6 months afterwards on those without a history of TB or a positive PPD. Demographic, occupational, and TB exposure data also were collected. SETTING: Outpatient clinics, hospitals, private practice offices, and drug treatment programs providing HIV-related healthcare and research programs. PARTICIPANTS: A voluntary sample of staff and volunteers from 16 Community Programs for Clinical Research on AIDS units. RESULTS: Factors related to prior TB or a positive skin test at baseline included being foreign-born, increased length of time in health care, living in New York City, or previous bacille Calmette-Guerin vaccination. The rate of PPD conversion was 1.8 per 100 person years of follow-up. No independent relation was found between the amount or type of contact with HIV-infected populations and the risk of TB infection. CONCLUSION: These data provide some reassurance that caring for HIV-infected patients is not related to an increased rate of TB infection among HCWs in these settings.     

Evaluation of guidelines for initiation of highly active antiretroviral therapy in a longitudinal cohort of HIV-infected individuals

OBJECTIVES: Expert panels have developed several guidelines for initiating highly active antiretroviral therapy (HAART) in patients with HIV infection. To evaluate these guidelines, we simulated their application in a cohort of HIV-infected patients established and followed before HAART was available, and determined how long such patients survived without disease progression in the absence of HAART. METHODS: Longitudinal data was used that had been collected from 1982 to 1995 on a prospective cohort of 133 homosexual men with known or closely approximated dates of HIV-1 seroconversion and negligible antiretroviral exposure. The main definition of disease progression was CD4 cell count < or = 300x10(6)/l or development of clinical AIDS diagnosis within 12 months. RESULTS: The mean number of years between the recommended initiation of therapy and when disease progression occurred in the absence of HAART were as follows: initiation of treatment at first visit, 4.81 years [median, 3.78 years; interquartile range (IQR), 1.85-6.59 years]; CD4 cell count <500x10(6)/l or serum RNA >5000 copies/ml (at least 10000 copies/ml fresh plasma), 4.35 years (median, 3.22 years; IQR, 1.56-6.19 years); CD4 cells <500x10(6)/l or serum RNA >20000 copies/ml (at least 40000 copies/ml fresh plasma), 3.61 years (median, 2.70 years; IQR, 1.40-5.11 years); and CD4 cells <500x10(6)/l, 2.72 years (median, 2.17 years; IQR, 0.81-4.25 years). The percentage of patients who had disease progression before HAART would have been recommended was 0.8, 1.6, 3.2 and 13.6% with each of these four approaches, respectively. CONCLUSIONS: Implementation of recommended treatment guidelines will result in a substantial proportion of patients being treated for long periods before immunologic or clinical disease progression would have occurred in the absence of HAART. These findings should be considered in the clinical care of HIV-infected patients and in future recommendations for the initiation of HAART.     

Comparative effectiveness of social problem-solving therapy and reminiscence therapy as treatments for depression in older adults.

Compared the effects of 2 psychotherapies based on divergent conceptualizations of depression in later life. 75 older adults diagnosed with major depressive disorder were assigned randomly to problem-solving therapy (PST), reminiscence therapy (RT), or a waiting-list control (WLC) condition. Participants in PST and RT were provided with 12 weekly sessions of group treatment. Dependent measures, taken at baseline, posttreatment, and 3-mo follow-up, included self-report and observer-based assessments of depressive symptomatology. At posttreatment, both the PST and the RT conditions produced significant reductions in depressive symptoms, compared with the WLC group, and PST Ss experienced significantly less depression than RT Ss. Moreover, a significantly greater proportion of Ss in PST vs RT demonstrated sufficient positive change to warrant classification of their depression as improved or in remission at the posttreatment and follow-up evaluations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prediction of response to treatment in a randomized clinical trial of marital therapy.

This study investigated demographic, intrapersonal, and interpersonal predictors of treatment response in a randomized clinical trial of 134 distressed married couples, which examined traditional (N. S. Jacobson & G. Margolin, 1979) and integrative (N. S. Jacobson & A. Christensen, 1996) behavioral couple therapy. Results based on hierarchical linear modeling revealed that interpersonal variables were the strongest predictors, but their effects were largely limited to predicting initial marital dissatisfaction; greater individual mental health was also associated with less distress initially. Couples who were married longer demonstrated stronger treatment gains, and exploratory analyses suggested that sexually dissatisfied couples showed slower initial, but overall more consistent, gains in the integrative versus the traditional approach. Findings are considered in light of the previous literature on predicting response to marital therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapists, therapist variables, and cognitive-behavioral therapy outcome in a multicenter trial for panic disorder.

The relationship between therapists and treatment outcome was examined in 14 highly trained therapists who participated in the Multicenter Collaborative Study for the Treatment of Panic Disorder. Overall, therapists yielded positive outcomes in their caseloads; yet, therapists significantly differed in the magnitude of change among caseloads. Effect sizes for therapist impact on outcome measures varied from 0% to 18%. Overall experience in conducting psychotherapy was related to outcome on some measures, whereas age, gender, gender match, and experience with cognitive-behavioral therapy (CBT) were not. Therapists with above- and below-average outcomes were rated similarly on measures of adherence and competency. The results suggest that therapists make a contribution to outcome in CBT for panic disorder, even when patients are relatively uniform, treatment is structured, and outcome is positive. Implications for future clinical outcome studies and for training clinicians are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Efficacy of an acceptance-based behavior therapy for generalized anxiety disorder: Evaluation in a randomized controlled trial.

Generalized anxiety disorder (GAD) is a chronic anxiety disorder, associated with comorbidity and impairment in quality of life, for which improved psychosocial treatments are needed. GAD is also associated with reactivity to and avoidance of internal experiences. The current study examined the efficacy of an acceptance-based behavioral therapy aimed at increasing acceptance of internal experiences and encouraging action in valued domains for GAD. Clients were randomly assigned to immediate (n = 15) or delayed (n = 16) treatment. Acceptance-based behavior therapy led to statistically significant reductions in clinician-rated and self-reported GAD symptoms that were maintained at 3- and 9-month follow-up assessments; significant reductions in depressive symptoms were also observed. At posttreatment assessment 78% of treated participants no longer met criteria for GAD and 77% achieved high end-state functioning; these proportions stayed constant or increased over time. As predicted, treatment was associated with decreases in experiential avoidance and increases in mindfulness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of treatment compliance on outcome in cognitive-behavioral therapy for panic disorder: Quality versus quantity.

Cognitive-behavioral therapy (CBT) is skill based and assumes active patient participation in regard to treatment-related assignments. The effects of patient compliance in CBT outcome studies are equivocal, however, and 1 gap in the literature concerns the need to account for the quality versus the quantity of assigned work. In this study, both quality and quantity of home-based practice were assessed to better evaluate the effects of treatment compliance in patients with panic disorder (N?=?48) who participated in a 12-session CBT protocol. Patient estimates of compliance were not significantly associated with most outcome measures. On the other hand, therapist ratings of compliance significantly predicted positive changes on most outcome measures. Moreover, therapist and independent rater estimates of the quality of the participant's work, relative to the quantity of the work, were relatively better predictors of outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multidimensional family therapy for young adolescent substance abuse: Twelve-month outcomes of a randomized controlled trial.

Research has established the dangers of early onset substance use for young adolescents and its links to a host of developmental problems. Because critical developmental detours can begin or be exacerbated during early adolescence, specialized interventions that target known risk and protective factors in this period are needed. This controlled trial (n = 83) provided an experimental test comparing multidimensional family therapy (MDFT) and a peer group intervention with young teens. Participants were clinically referred, were of low income, and were mostly ethnic minority adolescents (average age = 13.73 years). Treatments were manual guided, lasted 4 months, and were delivered by community agency therapists. Adolescents and parents were assessed at intake, at 6-weeks post-intake, at discharge, and at 6 and 12 months following treatment intake. Latent growth curve modeling analyses demonstrated the superior effectiveness of MDFT over the 12-month follow-up in reducing substance use (effect size: substance use frequency, d = 0.77; substance use problems, d = 0.74), delinquency (d = 0.31), and internalized distress (d = 0.54), and in reducing risk in family, peer, and school domains (d = 0.27, 0.67, and 0.35, respectively) among young adolescents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polymerase chain reaction in the diagnosis of tuberculosis. Comparison of two target sequences for amplification

Amplification of a 340 bp sequence of the 38 kDa protein gene of Mycobacterium tuberculosis by the polymerase chain reaction has been developed. The sensitivity of this PCR was shown to be 10 fg both by agarose gel electrophoresis and Southern blot hybridisation being equivalent to 2-3 organisms and highly specific to M. tuberculosis and excluding even M. tuberculosis H37Ra and Mycobacterium bovis BCG. Sputum samples from patients with pulmonary tuberculosis gave a positivity rate of 45%. PCR was also performed using pt8 and pt9 primers which amplified a 541 bp sequence of IS6110. 41% of the above samples gave positive amplification. Three samples that were positive for 38 kDa sequence were negative for IS6110.     

Intensification of treatment for adults with acute lymphoblastic leukaemia: results of U.K. Medical Research Council randomized trial UKALL XA. Medical Research Council Working Party on Leukaemia in Adults

The effects of short-chain alcohols (methanol, ethanol and n-propanol) on the fast-inactivating, A-type, potassium current of Lymnaea neurons were examined using macroscopic recording techniques. Alcohols produced a blockade of the current and modified its inactivation mechanism. The extracellular concentrations of methanol, ethanol and n-propanol causing 50% suppression of the current were 2970, 830 and 230 mM, respectively. The main effects of alcohols on inactivation were a decrease in the amplitude of the fast component and a simultaneous increase in the amplitude of the slow component of inactivation. In a model, the suppression of the fast component could be reproduced by an increase of the backward rate constant related to the dissociation of the inactivation particle from its binding site. The blockade and modification of inactivation reveal similar dependences on ethanol concentration, indicating that the same type of interaction of ethanol with the channel underlies both of these events. Ethanol was effective only in extracellular applications. The data support an action of alcohols at a hydrophobic site near the extracellular portion of the channel.     

Multisystemic therapy for adolescents with poorly controlled type I diabetes: Stability of treatment effects in a randomized controlled trial.

The primary purpose of the present study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, improved regimen adherence, metabolic control, and rates of hospitalization for diabetic ketoacidosis (DKA) among adolescents with chronically poorly controlled Type 1 diabetes 6 months after the completion of treatment. A randomized controlled trial was conducted with 127 adolescents and their families. Mean participant age was 13.2 years. Sixty-three percent of participants were African American, and 51% were female. Data were collected at baseline, treatment termination, and 6-month follow-up. Changes in glycated hemoglobin (HbA1c), frequency of blood glucose testing (BGT), and rate of DKA admissions were assessed. In intent-to-treat analyses, a main effect of MST on DKA admissions was found at both treatment termination and follow-up. Improvements in BGT were moderated by family composition; only 2-parent MST families maintained improvements at follow-up. Improvements in HbA1c for the MST group at treatment termination were lost at follow-up. Results show that intensive, home-based psychotherapy created stable reductions in serious lapses in adherence, as indexed by episodes of DKA, among youth with poorly controlled diabetes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)