Parenting for lifelong health:A pragmatic cluster randomised controlled trial of a non-commercialised parenting programme for adolescents and their families in South Africa

Objective To assess the impact of ‘Parenting for Lifelong Health: Sinovuyo Teen’, a parenting programme for adolescents in low- and middle-income countries, on abuse and parenting practices. Design Pragmatic cluster randomised control trial. Setting 40 villages/urban sites (clusters) in the Eastern Cape province, South Africa. Participants 552 families reporting conflict with their adolescents (aged 10-18). Intervention Intervention clusters (n=20) received a 14-session parent and adolescent programme delivered by trained community members. Control clusters (n=20) received a hygiene and hand-washing promotion programme. Main outcome measures Primary outcomes: abuse and parenting practices at one and 5-9 months post-intervention. Secondary outcomes: Caregiver and adolescent mental health and substance use, adolescent behavioural problems, social support, exposure to community violence, and family financial wellbeing at 5-9 months post-intervention. Blinding was not possible. Results At 5-9 months post-intervention, the intervention was associated with lower abuse (caregiver report incidence rate ratio (IRR) 0.55 (95% CI 0.40 to 0.75, p Conclusions This parenting programme shows promise for reducing violence, improving parenting and family functioning in low-resource settings.</p

A parenting programme to prevent abuse of adolescents in South Africa:Study protocol for a randomised controlled trial

An estimated one billion children experience child abuse each year, with the highest rates in low- and middle-income countries. The Sinovuyo Teen programme is part of Parenting for Lifelong Health, a WHO/UNICEF initiative to develop and test violence-prevention programmes for implementation in low-resource contexts. The objectives of this parenting support programme are to prevent the abuse of adolescents, improve parenting and reduce adolescent behavioural problems. This trial aims to evaluate the effectiveness of Sinovuyo Teen compared to an attention-control group of a water hygiene programme.This is a pragmatic cluster randomised controlled trial, with stratified randomisation of 37 settlements (rural and peri-urban) with 40 study clusters in the Eastern Cape of South Africa. Settlements receive either a 14-session parenting support programme or a 1-day water hygiene programme. The primary outcomes are child abuse and parenting practices, and secondary outcomes include adolescent behavioural problems, mental health and social support. Concurrent process evaluation and qualitative research are conducted. Outcomes are reported by both primary caregivers and adolescents. Brief follow-up measures are collected immediately after the intervention, and full follow-up measures collected at 3-8 months post-intervention. A 15-24-month follow-up is planned, but this will depend on the financial and practical feasibility given delays related to high levels of ongoing civil and political violence in the research sites.This is the first known trial of a parenting programme to prevent abuse of adolescents in a low- or middle-income country. The study will also examine potential mediating pathways and moderating factors. Pan-African Clinical Trials Registry PACTR201507001119966

Reducing child abuse amongst adolescents in low- and middle-income countries:A pre-post trial in South Africa

Background: No known studies have tested the effectiveness of child abuse prevention programmes for adolescents in low- or middle-income countries. ‘Parenting for Lifelong Health’ (http://tiny.cc/whoPLH) is a collaborative project to develop and rigorously test abuse-prevention parenting programmes for free use in low-resource contexts. Research aims of this first pre-post trial in South Africa were: i) to identify indicative effects of the programme on child abuse and related outcomes; ii) to investigate programme safety for testing in a future randomised trial, and iii) to identify potential adaptations. Methods: 230 participants (adolescents and their primary caregivers) were recruited from schools, welfare services and community-sampling in rural, high-poverty South Africa (no exclusion criteria). All participated in a 12-week parenting programme, implemented by local NGO childcare workers to ensure real-world external validity. Standardised pre-post measures with adolescents and caregivers were used, and paired t-tests were conducted for primary outcomes: abuse (physical, emotional and neglect), adolescent behaviour problems and parenting (positive and involved parenting, poor monitoring and inconsistent discipline), and secondary outcomes: mental health, social support and substance use. Results: Participants reported high levels of socio-economic deprivation, e.g. 60% of adolescents had either an HIV-positive caregiver or were orphaned by AIDS, and 50% of caregivers experienced intimate partner violence. i) indicative effects: Primary outcomes comparing pre-test and post-test assessments showed reductions reported by adolescents and caregivers in child abuse (adolescent report 63.0% pre-test to 29.5% post-test, caregiver report 75.5% pre-test to 36.5% post-test, both p&lt;0.001) poor monitoring/inconsistent discipline (p&lt;.001), adolescent delinquency/ aggressive behaviour (both p&lt;.001), and improvements in positive/involved parenting (p&lt;.01 adolescent report, p&lt;.001 caregiver report). Secondary outcomes showed improved social support (p&lt;.001 adolescent and caregiver reports), reduced parental and adolescent depression (both p&lt;.001), parenting stress (p&lt;.001 caregiver report) and caregiver substance use (p&lt;.002 caregiver report). There were no changes in adolescent substance use. No negative effects were detected. ii) Programme acceptability and attendance was high. There was unanticipated programme diffusion within some study villages, with families initiating parenting groups in churches, and diffusion through school assemblies and religious sermons. iii) potential adaptations identified included the need to strengthen components on adolescent substance use and to consider how to support spontaneous programme diffusion with fidelity. Conclusions: The programme showed no signs of harm and initial evidence of reductions in child abuse and improved caregiver and adolescent outcomes. It showed high acceptability and unexpected community-level diffusion. Findings indicate needs for adaptations, and suitability for the next research step of more rigorous testing in randomised trials, using cluster randomization to allow for diffusion effects

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A therapeutic HIV-1 vaccine reduces markers of systemic immune activation and latent infection in patients under highly active antiretroviral therapy

•Immune assays were performed on HIV-1 patients receiving therapeutic vaccine HIVAX.•HIVAX reduced the latent viral pool as measured by 2-LTR circles and total HIV-1 DNA.•HIVAX reduced serum cytokines and cellular markers of systemic immune activation.•HIVAX increased markers of activation on gag-specific CD4 + T cells.•HIVAX may suppress immune activation and latent infection in HIV-1 infected patients. HIV infection is characterized by chronic immune activation and the establishment of a pool of latently infected cells. Antiretroviral therapy (ART) can suppress viral load to undetectable levels in peripheral blood by standard measure, however immune activation/chronic inflammation and latent infection persist and affect quality of life. We have now shown that a novel therapeutic HIV vaccine consisting of replication-defective HIV (HIVAX), given in the context of viral suppression under ART, can reduce both immune activation/chronic inflammation and latent infection. Immune activation, as measured by percent of CD8 + HLA-DR + CD38 + T cells, approached levels of healthy controls at week 16 following vaccination. Reduced immune activation was accompanied by a reduction in pro-inflammatory cytokines and peripheral α4β7 + plasmacytoid DC (a marker of mucosal immune activation). Levels of both HIV-1 DNA and 2-LTR circles were reduced at week 16 following vaccination, suggesting HIVAX can impact HIV-1 latency and reduce viral replication. Surprisingly, reduced immune activation/chronic inflammation was accompanied by an increase in the percent of memory CD4 + T cells expressing markers PD-1 and TIM-3. In addition, evaluation of HIV-1 Gag-specific CD4 + T cells for expression of 96 T cell related genes pre- and post-therapy revealed increased expression of a number of genes involved in the regulation of immune activation, T cell activation, and antiviral responses. Overall this study provides evidence that vaccination with HIVAX in subjects under long term antiviral suppression can reduce immune activation/chronic inflammation and latent infection (Clinicaltrials.gov, identifier NCT01428596)

Additional file 1: of A parenting programme to prevent abuse of adolescents in South Africa: study protocol for a randomised controlled trial

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol. (DOC 122 KB

Patterns of Opacification in Coronary CT Angiography: Contrast Differences and Gradients

Iodinated contrast delivery is a key component of coronary CT angiography. However, the purpose of contrast delivery has been limited to morphology alone. Specifically, iodine opacification of the coronary lumen has been used to separate it from the coronary artery wall and lesions within the coronary arteries. Because contrast is delivered to the coronary arteries according to the coronary blood flow, there is flow information encoded within the contrast opacification which, depending on CT hardware and acquisition protocol, can be recognized in coronary CT angiography. In addition, metrics related to flow have been identified and studied. They include coronary contrast opacification differences and contrast opacification gradients