T cell cytokine responses in persons with tuberculosis and human immunodeficiency virus infection

Tuberculosis causes more extensive and life-threatening disease in patients with HIV infection than in immunocompetent persons. To investigate the hypothesis that these severe manifestations of tuberculosis may be due to alterations in cytokine production, we evaluated cytokine patterns in HIV-infected tuberculosis patients. Upon stimulation with Mycobacterium tuberculosis in vitro, PBMC from HIV-infected tuberculosis patients had reduced proliferative and type 1 responses, compared with HIV-seronegative tuberculosis patients. The reduction in proliferative responses was independent of the CD4 cell count, but the reduced type 1 response was a direct result of CD4 cell depletion. There was no enhancement of type 2 cytokine production in HIV-infected patients, although production of IL-10 was prominent in all tuberculosis patients. In HIV-infected tuberculosis patients, M. tuberculosis-induced proliferative responses were significantly enhanced by neutralizing antibodies to IL-10 but not by antibodies to IL-4 or by recombinant IL-12. The M. tuberculosis-induced type 1 response was augmented both by antibodies to IL-10 and by recombinant IL-12. Tuberculosis in the context of HIV infection is characterized by diminished type 1 responses, probably induced by immunosuppressive cytokines produced by macrophages/monocytes, rather than by type 2 cells.     

Protection from Mycobacterium avium complex disease in human immunodeficiency virus-infected persons with a history of tuberculosis

Risk of Mycobacterium avium complex disease was examined in human immunodeficiency virus (HIV)-infected patients with and without a history of tuberculosis. Information was obtained by retrospective review of charts of patients in HIV clinics in 10 US cities. Among 1363 patients with <200 CD4 cells/mm3 seen at Grady Memorial Hospital (GMH), 11 (17%) of 66 with a history of a positive purified protein derivative (PPD) skin test acquired M. avium infection, while 29 (16%) of 185 who were PPD-negative (but not anergic) did not (P = .85). Only 4 (8%) of 49 GMH patients with a history of tuberculosis acquired M. avium infection compared with 252 (19%) of 1314 GMH patients without a history of tuberculosis (P = .05). Proportional hazards analysis of risk factors for M. avium infection among 441 persons with and 8702 persons without a history of tuberculosis in 9 other cities confirmed protection from M. avium infection in persons with a history of tuberculosis (relative risk, 0.52; 95% confidence interval, 0.36-0.76; P < .001). Prior tuberculosis provides protection against M. avium infection in HIV-infected persons, possibly by stimulation of antimycobacterial immunity.     

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.     

Parents and procedures: a randomized controlled trial

INTRODUCTION: Previous work has shown that parents prefer to be present when their children undergo common invasive procedures, although physicians are ambivalent about parental presence. PURPOSE: To determine the effect of a parent-focused intervention on the pain and performance of the procedure, anxiety of parents and clinicians, and parental satisfaction with care. POPULATION: Children younger than 3 years old undergoing venipuncture, intravenous cannulation, or uretheral catheterization. SETTING: Pediatric emergency department of Boston City Hospital. DESIGN: Randomized controlled trial with three groups; parents present and given instructions on how to help their children; parents present, but no instructions given; and parents not present. INTERVENTION: The parents were instructed to touch, talk to, and maintain eye contact during the procedure. RESULTS: A total of 431 parents was randomized to the intervention (N = 153), present (N = 147), and not present (N = 131) groups. The groups were equivalent with respect to measured sociodemographic variables and parents' previous experience in the pediatric emergency department. No differences emerged with respect to pain (3-point scale measured by parent and clinician, and analysis of cry); performance of the procedure (number of attempts, completion of procedure by first clinician, time); clinician anxiety; or parental satisfaction with care. Parents who were present were more likely to rate the pain of the children as extreme/severe (52%) in comparison to clinicians (15%, kappa .07, poor agreement) and were significantly less anxious than parents who were not present. CONCLUSION: Overall, the intervention was not effective in reducing the pain of routine procedures. Parental presence did not negatively affect performance of the procedure or increase clinician anxiety. Parents who were present were less anxious than those who were not present. CLINICAL IMPLICATION: In general, parents have indicated that they want to be present when their children undergo procedures. The results of this study challenge the traditional belief that parental presence negatively affects our ability to successfully complete procedures. We should encourage parents who want to be present to stay during procedures.     

Reduction in disability in a randomized controlled trial of telephone-administered cognitive-behavioral therapy.

Objective: The authors examined the efficacy of telephone-administered cognitive-behavioral therapy (T-CBT) and telephone-administered supportive emotion-focused therapy (T-SEFT) in reducing disability among disabled patients with multiple sclerosis and depression. Telephone administration of therapy allowed care to be delivered to a more disabled population. This is a secondary analysis of a randomized controlled trial; the primary outcome results for depression are reported in D. C. Mohr, S. L. Hart, L. Julian, C. Catledge, L. Honos-Webb, L. Vella, et al. (2005). Design: A randomized controlled trial, comparing 16 weeks of T-CBT with T-SEFT. Main Outcome Measures: Disability was measured using Guy's Neurological Disability Scale; fatigue was measured using the Fatigue Impact Scale; depression was measured using the Hamilton Depression Rating Scale and the Beck Depression Inventory-II. Results: Patients in both treatments showed significant improvements in disability and fatigue. These improvements were related to reductions in depression. T-CBT produced significantly greater decreases in disability and fatigue, compared with T-SEFT, even after controlling for depression. The greater benefit of T-CBT on disability was mediated by physical fatigue. Conclusion: These findings support the hypothesis that significant reductions in disability can be achieved by reducing depression in patients with multiple sclerosis. There was also evidence that further reductions could be achieved through CBT-specific interventions that include a focus on symptoms such as fatigue management. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

A randomized controlled trial comparing two vocational models for persons with severe mental illness.

The authors compared 2 approaches to vocational rehabilitation for individuals with severe mental illness: the individual placement and support (IPS) model of supported employment and the diversified placement approach (DPA), which emphasizes work readiness and offers a range of vocational options, including agency-run businesses and agency-contracted placements with community employers. In all, 187 unemployed participants with severe mental illness were randomly assigned to IPS or DPA. Over 2 years, IPS had significantly better competitive employment outcomes than DPA. Competitive employment rates over the 2-year follow-up were 75.0% for IPS and 33.7% for DPA. However, IPS and DPA did not differ on paid employment outcomes. The authors conclude that IPS is more effective than DPA in achieving competitive employment, but not paid employment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preventing sleep problems in infants: a randomized controlled trial

In the pre-school years sleep problems are one of the most common subjects on which parents seek advice from health professionals. In the majority of cases a sleepless child causes significant stress within the family, and if parents do not obtain sufficient sleep this can have a detrimental effect on their physical and emotional well-being. In a small number of cases a child who wakes frequently and will not settle back to sleep may be at risk of physical abuse. In recent years it has been suggested that it may be possible to prevent sleep problems developing by providing parents with advice in the post-natal period. Parents have stated that they find this type of intervention helpful, however, there has been no attempt to establish whether a preventive approach is effective. The aim of this research was to evaluate the efficacy of health education in reducing the incidence of sleep problems. Adopting an experimental approach, participants were randomly allocated to a control group or an intervention group. Parental knowledge of sleep and settling behaviour was manipulated when the children in the intervention group were 3 months old. The sleeping behaviour of the infants in both groups was compared 6 months later, when the children were 9 months old. Data was collected from 86 families in the intervention group and 83 families in the control group. A comprehensive analysis of the sleeping behaviour demonstrated that a significantly smaller percentage of babies in the intervention group had settling and night-waking difficulties than in the control group.     

Brief cognitive therapy for panic disorder: A randomized controlled trial.

Cognitive therapy (CT) is a specific and highly effective treatment for panic disorder (PD). Treatment normally involves 12–15 1-hr sessions. In an attempt to produce a more cost-effective version, a briefer treatment that made extensive use of between-sessions patient self-study modules was created. Forty-three PD patients were randomly allocated to full CT (FCT), brief CT (BCT), or a 3-month wait list. FCT and BCT were superior to wait list on all measures, and the gains obtained in treatment were maintained at 12-month follow-up. There were no significant differences between FCT and BCT. Both treatments had large (approximately 3.0) and essentially identical effect sizes. BCT required 6.5 hr of therapist time, including booster sessions. Patients' initial expectation of therapy success was negatively correlated with posttreatment panic-anxiety. Cognitive measures at the end of treatment predicted panic-anxiety at 12-month follow-up. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Computerized behavior therapy for opioid-dependent outpatients: A randomized controlled trial.

The authors evaluated the efficacy of an interactive, computer-based behavioral therapy intervention, grounded in the community reinforcement approach (CRA) plus voucher-based contingency management model of behavior therapy. Our randomized, controlled trial was conducted at a university-based research clinic. Participants comprised 135 volunteer adult outpatients who met DSM-IV criteria for opioid dependence. All participants received maintenance treatment with buprenorphine and were randomly assigned to one of three treatments: (a) therapist-delivered CRA treatment with vouchers, (b) computer-assisted CRA treatment with vouchers, or (c) standard treatment. The therapist-delivered and computer-assisted CRA plus vouchers interventions produced comparable weeks of continuous opioid and cocaine abstinence (M = 7.98 and 7.78, respectively) and significantly greater weeks of abstinence than the standard intervention (M = 4.69; p     

Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals

Infection with HIV results in an incremental loss of T helper cell (TH) function, which can occur years before CD4 cell numbers are critically reduced and AIDS is diagnosed. All TH function is not affected, however, because B cell activation and hypergammaglobulinema are also characteristic of this period. Recently, in a murine model of AIDS an early loss in production of the CD4 cytokines IL-2 and IFN-gamma was correlated with an increase in the B cell stimulatory cytokines IL-4, IL-5, and IL-10. We therefore assessed the production of IL-4 generated by PBL from HIV-seropositive (HIV+) individuals who did not have AIDS, yet who exhibited different TH functional categories based on their IL-2 production profiles. We observed that the decreases in recall antigen-stimulated IL-2 production were accompanied by an increase in IL-4 production. The loss of recall antigen-stimulated responses in HIV+ individuals could be reversed in vitro by anti-IL-4 antibody. Our results suggest that the TH functions assessed by IL-4 production replace the normally dominant TH function of antigen-stimulated IL-2 production in the progression toward AIDS, and raise the possibility of cytokine cross-regulation in AIDS therapy.     

Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted diseases: a randomized controlled trial. Project RESPECT Study Group

CONTEXT: The efficacy of counseling to prevent infection with the human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) has not been definitively shown. OBJECTIVE: To compare the effects of 2 interactive HIV/STD counseling interventions with didactic prevention messages typical of current practice. DESIGN: Multicenter randomized controlled trial (Project RESPECT), with participants assigned to 1 of 3 individual face-to-face interventions. SETTING: Five public STD clinics (Baltimore, Md; Denver, Colo; Long Beach, Calif; Newark, NJ; and San Francisco, Calif) between July 1993 and September 1996. PARTICIPANTS: A total of 5758 heterosexual, HIV-negative patients aged 14 years or older who came for STD examinations. INTERVENTIONS: Arm 1 received enhanced counseling, 4 interactive theory-based sessions. Arm 2 received brief counseling, 2 interactive risk-reduction sessions. Arms 3 and 4 each received 2 brief didactic messages typical of current care. Arms 1, 2, and 3 were actively followed up after enrollment with questionnaires at 3, 6, 9, and 12 months and STD tests at 6 and 12 months. An intent-to-treat analysis was used to compare interventions. MAIN OUTCOME MEASURES: Self-reported condom use and new diagnoses of STDs (gonorrhea, chlamydia, syphilis, HIV) defined by laboratory tests. RESULTS: At the 3- and 6-month follow-up visits, self-reported 100% condom use was higher (P<.05) in both the enhanced counseling and brief counseling arms compared with participants in the didactic messages arm. Through the 6-month interval, 30% fewer participants had new STDs in both the enhanced counseling (7.2%; P= .002) and brief counseling (7.3%; P= .005) arms compared with those in the didactic messages arm (10.4%). Through the 12-month study, 20% fewer participants in each counseling intervention had new STDs compared with those in the didactic messages arm (P = .008). Consistently at each of the 5 study sites, STD incidence was lower in the counseling intervention arms than in the didactic messages intervention arm. Reduction of STD was similar for men and women and greater for adolescents and persons with an STD diagnosed at enrollment. CONCLUSIONS: Short counseling interventions using personalized risk reduction plans can increase condom use and prevent new STDs. Effective counseling can be conducted even in busy public clinics.     

Improving the quality of life of caregivers of persons with spinal cord injury: A randomized controlled trial.

Objective: To assess the efficacy of two psychosocial interventions for caregivers of older persons with spinal cord injury (SCI). Design: A multisite, three-group, randomized controlled trial comparing two active intervention conditions with each other and to an information-only control group. One hundred seventy-three caregiver and care-recipient dyads were randomly assigned to one of three conditions: a caregiver-only treatment condition in which caregivers received a multicomponent intervention based on their risk profile; a dual-target condition in which the caregiver intervention was complemented by a treatment targeting the care recipient, designed to address both caregiver and care recipient risk factors; and an information-only control condition in which the caregiver received standard printed information about caregiving, SCI, and aging. Outcome Measures: A multivariate outcome comprised of six indicators linked to the goals of the interventions was the primary outcome of the study. The multivariate outcome included measures of depressive symptoms, burden, social support and integration, self-care problems, and physical health symptoms. Results: At 12 months, caregivers in the dual-target condition had improved quality of life as measured by our multivariate outcome when compared to the control condition. Using the dyad as the unit of analysis, the dual-target condition was superior to both the control condition and the caregiver-only condition in our multivariate outcomes analysis. Dyads enrolled in the dual-target condition had significantly fewer health symptoms than control condition and caregiver-only condition participants and were less depressed when compared to participants in the caregiver-only condition. In follow-up analyses we found that a higher proportion of caregivers in the dual-target condition had clinically significant improvements in depression, burden, and health symptoms when compared with the caregiver-only condition. Conclusion: Caregivers are in need of and can benefit from interventions that help them manage the medical and functional limitations of the care recipient. Intervention strategies that target both the caregiver and care recipient are particularly promising strategies for improving the quality of life of caregivers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Outcome of subacute stroke rehabilitation: a randomized controlled trial

We compared the biological activity of a new group of keto-C-glycosides to that of a narrow spectrum of unsaturated ketonucleosides in a panel of non-small-cell lung cancer (NSCLC) cells with various levels of intrinsic resistance to standard chemotherapy drugs. Unlike cisplatin, etoposide, adriamycin, or taxol, for which a significant difference in the cytotoxic effect was observed between sensitive cell lines (H460, H125, and MGH4) and drug-resistant cell lines (H661, MGH7, and FADU), nucleoside analogs were equally cytotoxic in NSCLC cell lines, with compound 92 being 10-fold more active than compound 43, 44, 81, or 161, while compound 3 was the least active. Apoptotic measurements with flow cytometric analysis of terminal uridine deoxynucleotide nick end-labeled cells revealed that the cytotoxic activity of these nucleosides correlated with their potency to induce apoptosis. Compound 92 triggered death in cells with wild-type p53, mutated p53, or p53 gene deletion. Our findings suggest that keto-C-glycosides may be promising alternative anticancer agents which merit further studies in in vivo cancer models refractory to standard chemotherapy drugs.     

Cognitive-behavioral therapy for women with lifelong vaginismus: A randomized waiting-list controlled trial of efficacy.

Women with lifelong vaginismus (N = 117) were randomly assigned to cognitive-behavioral group therapy, cognitive-behavioral bibliotherapy, or a waiting list. Manualized treatment comprised sexual education, relaxation exercises, gradual exposure, cognitive therapy, and sensate focus therapy. Group therapy consisted of ten 2-hr sessions with 6 to 9 participants per group. Assistance with minimal-contact bibliotherapy consisted of 6 biweekly, 15-min telephone contacts. Twenty-one percent of the participants left the study before posttreatment assessment. Intent-to-treat analysis revealed that successful intercourse at posttreatment was reported by 14% of the treated participants compared with none of the participants in the control condition. At the 12-month follow-up 21% of the group therapy participants and 15% of the bibliotherapy participants, respectively, reported successful intercourse. Cognitive-behavioral treatment of lifelong vaginismus was thus found to be efficacious, but the small effect size of the treatment warrants future efforts to improve the treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: a pilot randomized clinical trial

The long-term outcome of pulmonary function was evaluated in farmer's lung (FL) patients compared to representative control farmers. This is, to our knowledge, the first such study which has included a control group. Clinical examinations were conducted in 89 FL patients and 84 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yrs. The mean transfer factor of the lung for carbon monoxide (TL,CO) was on average 12% lower (p < 0.001) in FL patients compared to control farmers. In spirometry, the mean maximum expiratory flow at 50% of vital capacity (MEF50) was lower (p = 0.08) in FL patients but there were no differences in mean vital capacity (VC) or forced expiratory volume in one second (FEV1) between FL patients and control farmers. However, airway obstruction, defined as an FEV1/VC less than 88% of predicted, was more common in FL patients than in control farmers (33 versus 17%; p = 0.02). Patients who had had recurrent episodes of FL had a significantly lower mean TL,CO compared to those FL patients who had experienced only a single episode. In conclusion, impairment of the pulmonary transfer factor is the most important long-term consequence of farmer's lung. However, farmer's lung may also lead to development of airway obstruction.     

Therapeutic efficacy of tirilazad in experimental multiple cerebral emboli: a randomized, controlled trial

OBJECTIVE: A significant proportion of patients who undergo cardiac surgery or carotid endarterectomy appear to develop subtle cognitive deficits, with the occurrence of multiple cerebral microemboli documented by Doppler ultrasound during these procedures. We used an experimental multiple cerebral embolism model to test whether treatment with tirilazad (U74006F), a putative inhibitor of lipid peroxidation, would improve functional outcome after multiple brain emboli. DESIGN: Randomized, controlled trial. SETTING: Animal care facility procedure room. SUBJECTS: A total of 44 New Zealand White rabbits weighing 2 to 3.0 kg. INTERVENTIONS: Variable quantities of 125I-labeled 50-microns microspheres were injected via a carotid catheter to produce multifocal brain ischemia. Rabbits randomly received either: tirilazad (3 mg/kg i.v.) 5 mins before embolization (pretreatment), or 30 mins after embolization (posttreatment) followed by 1.5 mg/kg every 5 hrs x 3 doses. A third group received vehicle only (control) 5 mins before, followed by three doses every 5 hrs. MEASUREMENTS AND MAIN RESULTS: The animals were rated by a blinded observer at 18 hrs after ischemia and scored as either grossly abnormal/dead or normal. The animals were killed and the amount of microspheres in the brain that were required to produce abnormal function at 18 hrs was calculated for each group. To determine if tirilazad also modified leukocyte function during ischemia, neutrophil adhesion to laminin was determined at baseline and 18 hrs after ischemia using a myeloperoxidase assay. In this study, pretreatment, but not posttreatment with tirilazad produced a significant reduction in neurologic deficits. Tirilazad also attenuated postischemic increases in neutrophil adhesion. CONCLUSIONS: Tirilazad pretreatment reduces neurologic deficits from multiple cerebral emboli. This significant protective effect suggests that pretreatment with tirilazad may play a role in clinical situations where the risk of cerebral emboli is high, with changes in leukocyte adherence as a potential mechanism.