Adolescent Abstinence and Unprotected Sex in CyberSenga,an Internet-Based HIV Prevention Program: Randomized Clinical Trial of Efficacy

Context

Cost-effective, scalable programs are urgently needed in countries deeply affected by HIV.

Methods

This parallel-group RCT was conducted in four secondary schools in Mbarara, Uganda. Participants were 12 years and older, reported past-year computer or Internet use, and provided informed caregiver permission and youth assent. The intervention, CyberSenga, was a five-hour online healthy sexuality program. Half of the intervention group was further randomized to receive a booster at four-months post-intervention. The control arm received ‘treatment as usual’ (i.e., school-delivered sexuality programming). The main outcome measures were: 1) condom use and 2) abstinence in the past three months at six-months'' post-intervention. Secondary outcomes were: 1) condom use and 2) abstinence at three-month''s post-intervention; and 6-month outcomes by booster exposure. Analyses were intention to treat.

Results

All 416 eligible youth were invited to participate, 88% (n = 366) of whom enrolled. Participants were randomized to the intervention (n = 183) or control (n = 183) arm; 91 intervention participants were further randomized to the booster. No statistically significant results were noted among the main outcomes. Among the secondary outcomes: At three-month follow-up, trends suggested that intervention participants (81%) were more likely to be abstinent than control participants (74%; p = 0.08), and this was particularly true among youth who were abstinent at baseline (88% vs. 77%; p = 0.02). At six-month follow-up, those in the booster group (80%) reported higher rates of abstinence than youth in the intervention, no booster (57%) and control (55%) groups (p = 0.15); they also reported lower rates of unprotected sex (5%) compared to youth in the intervention, no booster (24%) and control (21%) groups (p = 0.21) among youth sexually active at baseline.

Conclusions

The CyberSenga program may affect HIV preventive behavior among abstinent youth in the short term and, with the booster, may also promote HIV preventive behavior among sexually active youth in the longer term.

Trial Registration

{"type":"clinical-trial","attrs":{"text":"NCT00906178","term_id":"NCT00906178"}}NCT00906178.     

Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville)

Objective

Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC.

Methods

In this study, registered at ClinicalTrials.Gov ({"type":"clinical-trial","attrs":{"text":"NCT00657397","term_id":"NCT00657397"}}NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively.

Results

In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively).

Conclusions

Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence.

Trial registration

Number Eudract 2008-001338-28; ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00657397","term_id":"NCT00657397"}}NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511     

Effect of a Community-Based Nursing Intervention on Mortality in Chronically Ill Older Adults: A Randomized Controlled Trial

Background

Improving the health of chronically ill older adults is a major challenge facing modern health care systems. A community-based nursing intervention developed by Health Quality Partners (HQP) was one of 15 different models of care coordination tested in randomized controlled trials within the Medicare Coordinated Care Demonstration (MCCD), a national US study. Evaluation of the HQP program began in 2002. The study reported here was designed to evaluate the survival impact of the HQP program versus usual care up to five years post-enrollment.

Methods and Findings

HQP enrolled 1,736 adults aged 65 and over, with one or more eligible chronic conditions (coronary artery disease, heart failure, diabetes, asthma, hypertension, or hyperlipidemia) during the first six years of the study. The intervention group (n = 873) was offered a comprehensive, integrated, and tightly managed system of care coordination, disease management, and preventive services provided by community-based nurse care managers working collaboratively with primary care providers. The control group (n = 863) received usual care. Overall, a 25% lower relative risk of death (hazard ratio [HR] 0.75 [95% CI 0.57–1.00], p = 0.047) was observed among intervention participants with 86 (9.9%) deaths in the intervention group and 111 (12.9%) deaths in the control group during a mean follow-up of 4.2 years. When covariates for sex, age group, primary diagnosis, perceived health, number of medications taken, hospital stays in the past 6 months, and tobacco use were included, the adjusted HR was 0.73 (95% CI 0.55–0.98, p = 0.033). Subgroup analyses did not demonstrate statistically significant interaction effects for any subgroup. No suspected program-related adverse events were identified.

Conclusions

The HQP model of community-based nurse care management appeared to reduce all-cause mortality in chronically ill older adults. Limitations of the study are that few low-income and non-white individuals were enrolled and implementation was in a single geographic region of the US. Additional research to confirm these findings and determine the model''s scalability and generalizability is warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01071967","term_id":"NCT01071967"}}NCT01071967 Please see later in the article for the Editors'' Summary     

The Outcomes of a 12-Week Internet Intervention Aimed at Improving Fitness and Health-Related Quality of Life in Overweight Adolescents: The Young & Active Controlled Trial

Background

Overweight and obesity among adolescents may have consequences, with potentially lasting effects on health and health-related quality of life (HRQoL). Excess weight is also associated with decreases in physical activity and cardiorespiratory fitness. The aim of the current study was to investigate the short-term effects of a 12-week Internet intervention in a primary care setting intended to increase cardiorespiratory fitness and HRQoL among overweight and obese adolescents.

Methods

In this controlled trial, participants (13–15 years) were non-randomly allocated to an intervention- or a control group. The intervention group received 12-weeks access to an online program providing tailored physical activity counseling based on principles from Self-determination Theory and Motivational Interviewing. The control group received standard follow-up by the school nurses. The primary outcome measure of cardiorespiratory fitness was determined using a shuttle run test. The secondary outcomes: HRQoL, leisure time exercise, body image and self-determined motivation for physical activity and exercise, were assessed by self-report measures. Age- and gender-adjusted body mass index (BMI) was calculated based on measurements of height and weight. To compare pre-to post intervention differences within groups, a paired samples t-test was used while crude differences between groups were analyzed with an independent samples t-test.

Results

Of the 120 participants, 108 completed the study, 75 in the intervention group and 33 in the control group. Exposure to the intervention had a small effect on cardiorespiratory fitness (0.14; 95% CI [0.01;0.28]; P = 0.04), and a moderate effect on HRQoL (5.22; 95% CI [0.90; 9.53]; P = 0.02). Moreover, the control group increased significantly in BMI, yielding a moderate preventive effect on BMI (−0.39; 95% CI [−0.74;−0.03]; P = 0.03) for the intervention group.

Conclusion

The results suggest that the Internet intervention with tailored physical activity counseling can have beneficial short-term effect on cardiorespiratory fitness, HRQoL and BMI among adolescents with overweight and obesity.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01700309","term_id":"NCT01700309"}}NCT01700309     

A Cluster Randomized-Controlled Trial of a Classroom-Based Drama Workshop Program to Improve Mental Health Outcomes among Immigrant and Refugee Youth in Special Classes

Objectives

The aim of this cluster randomized trial was to evaluate the effectiveness of a school-based theatre intervention program for immigrant and refugee youth in special classes for improving mental health and academic outcomes. The primary hypothesis was that students in the theatre intervention group would report a greater reduction in impairment from symptoms compared to students in the control and tutoring groups.

Methods

Special classrooms in five multiethnic high schools were randomly assigned to theater intervention (n = 10), tutoring (n = 10) or control status (n = 9), for a total of 477 participants. Students and teachers were non-blinded to group assignment. The primary outcome was impairment from emotional and behavioural symptoms assessed by the Impact Supplement of the Strengths and Difficulties Questionnaire (SDQ) completed by the adolescents. The secondary outcomes were the SDQ global scores (teacher and youth reports), impairment assessed by teachers and school performance. The effect of the interventions was assessed through linear mixed effect models which incorporate the correlation between students in the same class, due to the nature of the randomization of the interventions by classroom.

Results

The theatre intervention was not associated with a greater reduction in self-reported impairment and symptoms in youth placed in special class because of learning, emotional and behavioural difficulties than a tutoring intervention or a non-active control group. The estimates of the different models show a non-significant decrease in both self-reported and impairment scores in the theatre intervention group for the overall group, but the impairment score decreased significantly for first generation adolescents while it increased for second generation adolescents.

Conclusion

The difference between the population of immigrant and refugee youth newcomers studied previously and the sample of this trial may explain some of the differences in the observed impact of the theatre intervention.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01426451","term_id":"NCT01426451"}}NCT01426451     

In-Car Nocturnal Blue Light Exposure Improves Motorway Driving: A Randomized Controlled Trial

Prolonged wakefulness greatly decreases nocturnal driving performance. The development of in-car countermeasures is a future challenge to prevent sleep-related accidents. The aim of this study is to determine whether continuous exposure to monochromatic light in the short wavelengths (blue light), placed on the dashboard, improves night-time driving performance. In this randomized, double-blind, placebo-controlled, cross-over study, 48 healthy male participants (aged 20–50 years) drove 400 km (250 miles) on motorway during night-time. They randomly and consecutively received either continuous blue light exposure (GOLite, Philips, 468 nm) during driving or 2*200 mg of caffeine or placebo of caffeine before and during the break. Treatments were separated by at least 1 week. The outcomes were number of inappropriate line crossings (ILC) and mean standard deviation of the lateral position (SDLP). Eight participants (17%) complained about dazzle during blue light exposure and were removed from the analysis. Results from the 40 remaining participants (mean age ± SD: 32.9±11.1) showed that countermeasures reduced the number of inappropriate line crossings (ILC) (F(2,91.11) = 6.64; p<0.05). Indeed, ILC were lower with coffee (12.51 [95% CI, 5.86 to 19.66], p = 0.001) and blue light (14.58 [CI, 8.75 to 22.58], p = 0.003) than with placebo (26.42 [CI, 19.90 to 33.71]). Similar results were found for SDLP. Treatments did not modify the quality, quantity and timing of 3 subsequent nocturnal sleep episodes. Despite a lesser tolerance, a non-inferior efficacy of continuous nocturnal blue light exposure compared with caffeine suggests that this in-car countermeasure, used occasionally, could be used to fight nocturnal sleepiness at the wheel in blue light-tolerant drivers, whatever their age. More studies are needed to determine the reproducibility of data and to verify if it can be generalized to women.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01070004","term_id":"NCT01070004"}}NCT01070004     

Resistance to Erythropoiesis Stimulating Agents in Patients Treated with Online Hemodiafiltration and Ultrapure Low-Flux Hemodialysis: Results from a Randomized Controlled Trial (CONTRAST)

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; {"type":"clinical-trial","attrs":{"text":"NCT00205556","term_id":"NCT00205556"}}NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months'' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [−0.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (−2.52% [−4.72 to −0.31]; P = 0.02 and −49 ng/mL [−103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [−0.4 to 14.5]; P = 0.06).In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00205556","term_id":"NCT00205556"}}NCT00205556     

Effectiveness of a Randomized School-Based Intervention Involving Families and Teachers to Prevent Excessive Weight Gain among Adolescents in Brazil

Objective

To evaluate the effectiveness of a school-based intervention involving the families and teachers that aimed to promote healthy eating habits in adolescents; the ultimate aim of the intervention was to reduce the increase in body mass index (BMI) of the students.

Design

Paired cluster randomized school-based trial conducted with a sample of fifth graders.

Setting

Twenty classes were randomly assigned into either an intervention group or a control group.

Participants

From a total of 574 eligible students, 559 students participated in the study (intervention: 10 classes with 277 participants; control: 10 classes with 282 participants). The mean age of students was 11 years.

Intervention

Students attended 9 nutritional education sessions during the 2010 academic year. Parents/guardians and teachers received information on the same subjects.

Main Outcome Measurement

Changes in BMI and percentage of body fat.

Results

Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups (β = 0.003; p = 0.75). There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group; students in this group also consumed more fruits.

Conclusion

Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet, but this did not lead to a reduction in BMI gain. Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01046474","term_id":"NCT01046474"}}NCT01046474.     

The Immunologic Effects of Mesalamine in Treated HIV-Infected Individuals with Incomplete CD4+ T Cell Recovery: A Randomized Crossover Trial

The anti-inflammatory agent, mesalamine (5-aminosalicylic acid) has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT), has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm³ and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART) to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P  = 0.38 and P  = 0.63, respectively), or in the CD4+ T cell count at week 12 (P  = 0.83). The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P  = 0.86, P  = 0.84, respectively). During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01090102","term_id":"NCT01090102"}}NCT01090102     

Effectiveness of Cellulose Sulfate Vaginal Gel for the Prevention of HIV Infection: Results of a Phase III Trial in Nigeria

Background

This trial evaluated the safety and effectiveness of 6% cellulose sulfate vaginal gel in preventing male-to-female vaginal transmission of HIV, gonorrhea and chlamydial infection.

Methods

This Phase III, double-blind, randomized, placebo-controlled trial was conducted between November 2004 and March 2007 in Lagos and Port Harcourt, Nigeria. We enrolled 1644 HIV-antibody negative women at high risk of HIV acquisition. Study participants were randomized 1∶1 to cellulose sulfate or placebo and asked to use gel plus a condom for each act of vaginal intercourse over one year of follow-up. The participants were evaluated monthly for HIV, gonorrhea and chlamydial infection, and for adverse events.

Results

The trial was stopped prematurely after the data safety monitoring board of a parallel trial concluded that cellulose sulfate might be increasing the risk of HIV. In contrast, we observed fewer infections in the active arm (10) than on placebo (13), a difference that was nonetheless not statistically significant (HR = 0.8, 95% CI 0.3–1.8; p = 0.56). Rates of gonorrhea and chlamydial infection were lower in the CS group but the difference was likewise not statistically significant (HR = 0.8, 95% CI 0.5–1.1; p = 0.19 for the combined STI outcome). Rates of adverse events were similar across study arms. No serious adverse events related to cellulose sulfate use were reported.

Conclusions

Cellulose sulfate gel appeared to be safe in the evaluated study population but we found insufficient evidence that it prevented male-to-female vaginal transmission of HIV, gonorrhea or chlamydial infection. The early closure of the trial compromised the ability to draw definitive conclusions about the effectiveness of cellulose sulfate against HIV.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00120770","term_id":"NCT00120770"}}NCT00120770     

The Cameroon Mobile Phone SMS (CAMPS) Trial: A Randomized Trial of Text Messaging versus Usual Care for Adherence to Antiretroviral Therapy

Background

Mobile phone technology is a novel way of delivering health care and improving health outcomes. This trial investigates the use of motivational mobile phone text messages (SMS) to improve adherence to antiretroviral therapy (ART) over six months.

Methodology/Principal Findings

CAMPS was a single-site randomized two-arm parallel design trial in Yaoundé, Cameroon. We enrolled and randomized HIV-positive adults on ART, aged 21 years and above to receive a weekly standardized motivational text message versus usual care alone. The primary outcome was adherence measured using a visual analogue scale (VAS), number of doses missed (in the week preceding the interview) and pharmacy refill data. Outcomes were measured at 3 and 6 months. Service providers and outcome assessors were blinded to allocation. Analysis was by intention-to-treat. Between November and December 2010, 200 participants were randomized, with 101 in the intervention group and 99 in the control group. At 6 months, overall retention was 81.5%. We found no significant effect on adherence by VAS>95% (risk ratio [RR] 1.06, 95% confidence interval [CI] 0.89, 1.29; p = 0.542; reported missed doses (RR 1.01, 95% CI 0.87, 1.16; p>0.999) or number of pharmacy refills (mean difference [MD] 0.1, 95% CI: 0.23, 0.43; p = 0.617. One participant in the intervention arm reported a possible disclosure of status.

Conclusions/Significance

Standardized motivational mobile phone text messages did not significantly improve adherence to ART in this study. Other types of messaging or longer term studies are recommended.

Registration

1. Pan-African Clinical Trials Registry; PACTR201011000261458 2. Clinicaltrials.gov; {"type":"clinical-trial","attrs":{"text":"NCT01247181","term_id":"NCT01247181"}}NCT01247181     

Efficacy of a Group-Based Multimedia HIV Prevention Intervention for Drug-Involved Women under Community Supervision: Project WORTH

Importance

This study is designed to address the need for evidence-based HIV/STI prevention approaches for drug-involved women under criminal justice community supervision.

Objective

We tested the efficacy of a group-based traditional and multimedia HIV/STI prevention intervention (Project WORTH: Women on the Road to Health) among drug-involved women under community supervision.

Design, Setting, Participants, and Intervention

We randomized 306 women recruited from community supervision settings to receive either: (1) a four-session traditional group-based HIV/STI prevention intervention (traditional WORTH); (2) a four-session multimedia group-based HIV/STI prevention intervention that covered the same content as traditional WORTH but was delivered in a computerized format; or (3) a four-session group-based Wellness Promotion intervention that served as an attention control condition. The study examined whether the traditional or multimedia WORTH intervention was more efficacious in reducing risks when compared to Wellness Promotion; and whether multimedia WORTH was more efficacious in reducing risks when compared to traditional WORTH.

Main Outcomes and Measures

Primary outcomes were assessed over the 12-month post-intervention period and included the number of unprotected sex acts, the proportion of protected sex acts, and consistent condom use. At baseline, 77% of participants reported unprotected vaginal or anal sex (n = 237) and 63% (n = 194) had multiple sex partners.

Results

Women assigned to traditional or multimedia WORTH were significantly more likely than women assigned to the control condition to report an increase in the proportion of protected sex acts (β = 0.10; 95% CI = 0.02–0.18) and a decrease in the number of unprotected sex acts (IRR = 0.72; 95% CI = 0.57–0.90).

Conclusion and Relevance

The promising effects of traditional and multimedia WORTH on increasing condom use and high participation rates suggest that WORTH may be scaled up to redress the concentrated epidemics of HIV/STIs among drug-involved women in the criminal justice system.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01784809","term_id":"NCT01784809"}}NCT01784809     

WR279,396, a Third Generation Aminoglycoside Ointment for the Treatment of Leishmania major Cutaneous Leishmaniasis: A Phase 2, Randomized,Double Blind,Placebo Controlled Study

Background

Cutaneous leishmaniasis (CL) is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France.

Methods

A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180.

Results

Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity.

Conclusion

Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00703924","term_id":"NCT00703924"}}NCT00703924     

Efficacy of Enhanced HIV Counseling for Risk Reduction during Pregnancy and in the Postpartum Period: A Randomized Controlled Trial

Introduction

Pregnancy and the postpartum period present important intervention opportunities. Counseling can leverage the motivation women have during this time to change behaviors that may negatively affect their health and the heath of their infants.

Methods

Pregnant women attending an antenatal clinic in South Africa were randomly allocated to treatment (n = 733) and control arms (n = 747). Treatment arm participants received enhanced HIV pre- and post-test counseling, legal support and access to support groups at baseline, which occurred at the first antenatal visit, and then six and ten weeks postpartum. Control arm participants received standard HIV testing and counseling (HTC) and two postpartum attention control sessions. Outcomes were incidence of sexually transmitted infection (STI) by 14 weeks postpartum and past 30-day inconsistent condom use at 14 weeks and 9 months postpartum.

Results

There were no intervention effects on incident STIs for either HIV-negative (adjusted risk ratio (aRR) 1.01, 95% CI 0^.71–1^.44) or HIV-positive participants (aRR 0^.86, 95% CI 0^.61–1^.23). The intervention was associated with a 28% decrease in risk of past 30-day inconsistent condom use at nine-months among HIV-negative women (aRR 0^.72,95% CI 0^.59–0^.88), but did not affect inconsistent condom use among HIV-positive women (aRR1.08; 95% CI 0.67–1.75).

Discussion

An enhanced counseling intervention during pregnancy and the postpartum period can lead to reductions in inconsistent condom use among HIV-negative women. Results underscore the importance of the counseling that accompanies HIV HTC. More work is needed to understand how to promote and sustain risk reduction among HIV-positive women.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01683461","term_id":"NCT01683461"}}NCT01683461     

Improvement of Insulin Sensitivity by Isoenergy High Carbohydrate Traditional Asian Diet: A Randomized Controlled Pilot Feasibility Study

The prevalence of diabetes is rising dramatically among Asians, with increased consumption of the typical Western diet as one possible cause. We explored the metabolic responses in East Asian Americans (AA) and Caucasian Americans (CA) when transitioning from a traditional Asian diet (TAD) to a typical Western diet (TWD), which has not been reported before. This 16-week randomized control pilot feasibility study, included 28AA and 22CA who were at risk of developing type 2 diabetes. Eight weeks of TAD were provided to all participants, followed by 8 weeks of isoenergy TWD (intervention) or TAD (control). Anthropometric measures, lipid profile, insulin resistance and inflammatory markers were assessed. While on TAD, both AA and CA improved in insulin AUC (−960.2 µU/mL×h, P = 0.001) and reduced in weight (−1.6 kg; P<0.001), body fat (−1.7%, P<0.001) and trunk fat (−2.2%, P<0.001). Comparing changes from TAD to TWD, AA had a smaller weight gain (−1.8 to 0.3 kg, P<0.001) than CA (−1.4 to 0.9 kg, P = 0.001), but a greater increase in insulin AUC (AA: −1402.4 to 606.2 µU/mL×h, P = 0.015 vs CA: −466.0 to 223.5 µU/mL×h, P = 0.034) and homeostatic static model assessment-insulin resistance (HOMA-IR) (AA: −0.3 to 0.2, P = 0.042 vs CA: −0.1 to 0.0, P = 0.221). Despite efforts to maintain isoenergy state and consumption of similar energy, TAD induced weight loss and improved insulin sensitivity in both groups, while TWD worsened the metabolic profile. Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00379548","term_id":"NCT00379548"}}NCT00379548     

Effectiveness of a Multimodal Community Intervention Program to Prevent Suicide and Suicide Attempts: A Quasi-Experimental Study

Background

Multilevel and multimodal interventions have been suggested for suicide prevention. However, few studies have reported the outcomes of such interventions for suicidal behaviours.

Methods

We examined the effectiveness of a community-based multimodal intervention for suicide prevention in rural areas with high suicide rates, compared with a parallel prevention-as-usual control group, covering a total of 631,133 persons. The effectiveness was also examined in highly populated areas near metropolitan cities (1,319,972 persons). The intervention started in July 2006, and continued for 3.5 years. The primary outcome was the incidence of composite outcome, consisting of completed suicides and suicide attempts requiring admission to an emergency ward for critical care. We compared the rate ratios (RRs) of the outcomes adjusted by sex, age group, region, period and interaction terms. Analyses were performed on an intention-to-treat basis and stratified by sex and age groups.

Findings

In the rural areas, the overall median adherence of the intervention was significantly higher. The RR of the composite outcome in the intervention group decreased 7% compared with that of the control group. Subgroup analyses demonstrated heterogeneous effects among subpopulations: the RR of the composite outcome in the intervention group was significantly lower in males (RR = 0.77, 95% CI 0.59–0.998, p = 0.0485) and the RR of suicide attempts was significantly lower in males (RR = 0.39, 95% CI 0.22–0.68, p = 0.001) and the elderly (RR = 0.35, 95% CI 0.17–0.71, p = 0.004). The intervention had no effect on the RR of the composite outcome in the highly populated areas.

Interpretation

Our findings suggest that this community-based multimodal intervention for suicide prevention could be implemented in rural areas, but not in highly populated areas. The effectiveness of the intervention was shown for males and for the elderly in rural areas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00737165","term_id":"NCT00737165"}}NCT00737165 UMIN Clinical Trials Registry UMIN000000460     

A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (−0.6%, 95% CI, −1.1% to −0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications.This clinical trial was registered with ClinicalTrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT01713764","term_id":"NCT01713764"}}NCT01713764.     

Angiotensin Converting Enzyme Inhibitor and HMG-CoA Reductase Inhibitor as Adjunct Treatment for Persons with HIV Infection: A Feasibility Randomized Trial

Background

Treatments that reduce inflammation and cardiovascular disease (CVD) risk among individuals with HIV infection receiving effective antiretroviral therapy (ART) are needed.

Design and Methods

We conducted a 2×2 factorial feasibility study of lisinopril (L) (10 mg daily) vs L-placebo in combination with pravastatin (P) (20 mg daily) vs P-placebo among participants receiving ART with undetectable HIV RNA levels, a Framingham 10 year risk score (FRS) ≥3%, and no indication for ACE-I or statin therapy. Tolerability and adherence were evaluated. Longitudinal mixed models assessed changes in blood pressure (BP), blood lipids, and inflammatory biomarkers from baseline through months 1 and 4.

Results

Thirty-seven participants were randomized and 34 [lisinopril/pravastatin (n = 9), lisinopril/P-placebo (n = 8), L-placebo/pravastatin (n = 9), L-placebo/P-placebo (n = 8)] attended at least one follow-up visit. Participants were 97% male, 41% white, 67% were current smokers, and 65% were taking a protease inhibitor. Median age was 48 years, CD4 count 483 cells/mm³, FRS 7.79%, total cholesterol 184 mg/dL, and LDL-C 95 mg/dL. There was no treatment difference for pravastatin vs P-placebo in total cholesterol, LDL-C, or any of the inflammatory biomarkers. Participants randomized to lisinopril vs. L-placebo had significant declines in diastolic BP (−3.3 mmHg, p = 0.05), hsCRP (−0.61 µg/mL, p = 0.02) and TNF-α (−0.17 pg/mL, p = 0.04). Participants taking lisinopril vs L-placebo were more likely to report missed doses (88 vs 35%; p = 0.001) and have adherence <90% by pill count (42 vs. 0%; p = 0.02). Few participants from either group reported side effects (n = 3 vs. n = 1).

Conclusions

The modest BP changes and decreased adherence with lisinopril and absence of lipid differences with pravastatin suggest future studies of these drug classes should consider a run-in period to assess adherence and use a different statin. Our results also indicate that ACE-I therapy may have anti-inflammatory benefits for ART-treated persons with HIV infection and this should be further evaluated.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00982189","term_id":"NCT00982189"}}NCT00982189     

Oral Delivery of a Probiotic Induced Changes at the Nasal Mucosa of Seasonal Allergic Rhinitis Subjects after Local Allergen Challenge: A Randomised Clinical Trial

Objective

To determine effects of probiotic consumption on clinical and immunological parameters of seasonal allergic rhinitis (SAR) in an out-of-season single nasal allergen challenge.

Methods

In a study registered at ClinicalTrials.Gov ({"type":"clinical-trial","attrs":{"text":"NCT01123252","term_id":"NCT01123252"}}NCT01123252), a 16-week dietary intervention was undertaken in 60 patients with allergic rhinitis (>16 years old). Using a double-blinded, placebo-controlled anonymised design, the patients were divided equally into two groups. One group was given a dairy drink containing Lactobacillus casei Shirota to ingest daily while the other consumed a similar drink without bacteria. Participants attended the clinic on two consecutive days before the intervention and then again at the end of the study period. On the first day of each 2-day visit, following clinical examination, assessments were made of total nasal symptoms scores and peak nasal inspiratory flow. Nasal scrapings, nasal lavage and blood were collected for laboratory analyses of cellular phenotypes, soluble mediator release and in vitro responses to pollen allergen. These procedures were repeated 24 hours following nasal allergen challenge.

Results

Prior to and following intervention there were no detectable differences between study groups in measured clinical outcome. After intervention, there were differences between groups in their percentages of CD86+ epithelial cells (p = 0.0148), CD86+CD252+ non-epithelial cells (p = 0.0347), sIL-1RII release (p = 0.0289) and IL-1β (p = 0.0224) levels at the nasal mucosa. Delivery of probiotic also suppressed production of sCD23 (p = 0.0081), TGF-β (p = 0.0283) and induced increased production of IFN-γ (p = 0.0351) in supernatants of cultured peripheral blood.

Conclusions & Clinical Relevance

This study did not show significant probiotic-associated changes with respect to the primary clinical endpoint. An absence of overt clinical benefit may be due to an inability of single nasal challenges to accurately represent natural allergen exposure. Nevertheless, oral delivery of probiotics produced changes of the immunological microenvironment at the nasal mucosa in individuals affected by SAR.

Trial Registration

ClinicalTrials.Gov {"type":"clinical-trial","attrs":{"text":"NCT01123252","term_id":"NCT01123252"}}NCT01123252     

Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

Experimental studies suggested that statins attenuate vascular AT₁ receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00154024","term_id":"NCT00154024"}}NCT00154024