Project Empower

Abstract Pretomanid is a key component of the bedaquiline, pretomanid, linezolid with or without moxifloxacin (BPaL/M)regimen recommended for treatment of rifampicin-resistant tuberculosis (RR-TB). To support dose optimization and efficacy interpretation, we developed a pretomanid population pharmacokinetic (PK) model and evaluated exposure and probability of target attainment (PTA). Ninety-four RR-TB patients received daily oral pretomanid at 200 mg, and plasma samples were collected at multiple time points. Pretomanid concentrations were quantified using high-performance liquid chromatography-tandem mass spectrometry and PK modeling was performed using nlmixr2 in R. A one-compartment model with first-order absorption and elimination, and fat free mass allometric scaling best described the data. Typical clearance was 3.10 L/h, median AUC₀₋₂₄ was 63,733 μg·h/L, and median trough concentration was 1,965 μg/L. Pretomanid MICs for Mycobacterium tuberculosis in the TB-PRACTECAL trial were consistently below the provisional critical concentration, with a median of 0.125 mg/L. PK-Pharmacodynamic (PD) simulations indicated that nearly all participants achieved drug exposures exceeding %fT>MIC, supporting the regimen’s efficacy across the study population. We developed a pretomanid population PK model and facilitated exploring robust PK-PD targets for PTA that remain valuable to support dose optimisation. There is an urgent need for further research to identify the optimal clinically relevant PK-PD index for pretomanid, especially within the context of combination therapy.

Objectives/Goals: There has been a significant increase in the engagement of researchers with persons with lived and living experience, driven by a growing recognition of the invaluable insights and expertise these individuals bring to the research process. However, there remains a need for research teams to learn how to engage with patients and community partners. Methods/Study Population: The EMPOWER project is a collaborative of members with lived/living expertise of substance use during pregnancy. EMPOWER meets three times per month in support of their goals of patient-centered research, changing the narrative through conversations, and building the capacity of persons with lived experience to co-lead research. Through over 4 years of active collaboration and co-learning, EMPOWER has identified and created methods that support meaningful patient engagement and capacity building. Results/Anticipated Results: EMPOWER has identified the following methods that support meaningful engagement and capacity building: Mind-Mapping Exercises, Personal and Collective Journey Mapping, 8-month research training curriculum, Digital Storytelling, Learning Labs, and World Cafe Meetings. These methods have led to a collaborative of 20 individuals with lived experience of substance use to identify research gaps, prioritize research questions, design data collection tools, analyze research data, disseminate research results, and consult with healthcare teams in efforts to improve clinical care. To-date EMPOWER have given over 10 invited presentations and is currently writing manuscripts. Discussion/Significance of Impact: Meaningful patient and community engagement is critical to developing and implementing healthcare interventions. Unfortunately, engagement efforts are often lack in building capacity of patients and community, which impedes their ability to fully engage in all phases of research.

Recent evidence indicates that levofloxacin (LFX) is effective in preventing TB in individuals exposed to multidrug-resistant TB (MDR-TB). Despite the need for pediatric formulations, the 250 mg adult LFX formulation is affordable and widely used for TB treatment and prevention in children. TB-CHAMP (Tuberculosis Child Multidrug-resistant Preventive Therapy ISRCTN92634082) was a trial of MDR-TB preventive treatment, comparing levofloxacin to placebo in children with MDR-TB exposure. Acceptability questionnaires were administered to caregivers at six timepoints during the 24-week treatment phase. Likert scales were used to grade 6 domains of acceptability, and a composite acceptability (CA) outcome was generated. Factors associated with acceptability were assessed using modified Poisson regression models to estimate risk ratios (RRs). Overall, 922 children were randomised, 453 to LFX and 469 to placebo. By Week 8, 25.1% of children on LFX had poor CA versus 6.2% receiving placebo (Weeks 0-24: RR 3.43, 95% CI 2.69-4.37). Acceptability in the LFX arm improved from 36.8% poor CA at baseline to 12.9% at Week 24. Only 11.7% of children swallowing tablets whole/halved had poor CA outcomes at Week 8, compared to 34.4% swallowing crushed/softened tablets. LFX 250 mg tablets have reasonable acceptability and could be used as an alternative to dispersible formulations, especially in children able to swallow tablets.

Floods are increasing in frequency and may increase the risk for experiencing emotional distress, anxiety, depression and PTSD. The aim of this study was to determine the extent of damage, loss, injury and death resulting from floods that occurred in and around the city of Durban, South Africa, in April 2022, and associated changes in mental health pre- to post-floods in a low-income setting. Seventy-three women between the ages of 18 and 45, residing in flood affected, low-income settings, were interviewed prior to the floods occurring. Mental health measures were repeated with 69 of the 73 women during the post-flood interview along with a questionnaire measuring flood-related exposures. Loss of infrastructure (lacked access to drinking water, electricity, fresh food, could not travel to work, had to stay in a shelter and could not get hold of friends or family) was a predictor of post-flood change in levels of emotional distress and anxiety. Higher levels of prior trauma exposure were associated with higher post-flood levels of emotional distress. Higher pre-flood food insecurity was also associated with higher post-flood anxiety. Women affected by poverty, food insecurity and a history of trauma are vulnerable to the additive adverse mental health effects of floods. Proactive approaches to diminishing the impact of floods on the livelihood of women is needed and post-flood relieve efforts may be more affective if they are enhanced by providing mental health support.

Intimate partner violence (IPV) has a large and sustained impact on women’s mental health, and so effective prevention is critical. A review of 96 rigorous evaluations of interventions for their impact on violence against women and girls (mostly IPV) found that several intervention approaches were effective. However, not every evaluation of a ‘successful approach’ showed success in reducing IPV. In order to understand what else impacts success, we analysed practitioners’ accounts and documentation of the design and implementation of seventeen interventions evaluated as part of What Works to Prevent Violence against Women and Girls (VAWG). Six features were identified as characteristics of all successful interventions: a rigorously planned intervention with a robust theory of change (ToC), attuned to the local context; addressing multiple drivers of VAWG; support for survivors; working with women and men; implementing at optimal intensity and having sufficient, well-selected, trained and supported staff and volunteers. Four features were necessary for success when relevant for the intervention approach: gender and social empowerment group activities and promoting positive interpersonal relations; participatory learning methods, emphasising empowerment, critical reflection and communication skills; carefully designed user-friendly manuals systematically followed; and when working with children, having an age-appropriate design with time for learning and an engaging pedagogy. This analysis provides the IPV prevention field with critical information for enhancing the impact of group- and community-based interventions in IPV prevention and through this strengthening women’s mental health.

Participatory interventions with men and boys to transform masculinities are increasingly common to improve health and reduce intimate partner violence and HIV-related risk. Yet, despite this, there has been little consideration of how facilitators’ own masculinities shape interventions. In this analysis of Stepping Stones and Creating Futures, a gender-transformative programme delivered to young men (aged 18–30 years) in urban informal settlements in Durban, South Africa we explore how facilitators’ masculinities were employed to engender change in the masculinities of participants. We argue facilitators had to negotiate two tasks existing in some tension, the first, overt and the main aim of the programme: namely, challenging elements of the youthful masculinity at play in the lives of participants, such as exerting violent power over women. A second task was more covert: namely, establishing facilitators’ credibility ‘as men’ in order to do this work with participants. Through strategies including clothes, mobile phones, jokes and storytelling, facilitators demonstrated to participants their ‘successful’ masculinity and could then engage with participants around emotions, non-violence and consistent condom use. This enabled facilitators and participants to undergo a limited processes of change, without ‘compromising’ their sense of masculinity, and without fundamentally challenging men’s patriarchal privilege.

ABSTRACTUnconditional cash transfers have risen in prominence for their potential to improve the health of the world’s most marginalised and bring them into a relationship with the state. Typically, challenges to accessing grants are described in terms of technical issues such as access to documents and distance to offices. This paper explores the challenges of 30 young, poor, black South African women in accessing the Child Support Grant (CSG), an unconditional cash transfer provided by the South African government. Data suggest that while there were ‘technical’ issues, young women were systematically excluded from accessing the CSG in two ways. First, women were symbolically marginalised by state officials, who humiliated them, forcing women to sit quietly and acquiesce to state power to access the CSG. Second, there were large distances for women to travel to access state services, despite these being geared to serve the poor. Rather than promoting the active citizenship of the poorest in South Africa, accessing the CSG reinforced marginalisation. Transforming this will not be achieved through technical solutions, rather the barriers to access need to be recognised as political.

BackgroundPreventing intimate partner violence (IPV) remains a global public health challenge. Studies suggest urban informal settlements have particularly high levels of IPV and HIV-prevalence and these settlements are rapidly growing. The current evidence base of effective approaches to preventing IPV recognizes the potential of combining economic strengthening and gender transformative interventions. However, few of these interventions have been done in urban informal settlements, and almost none have included men as direct recipients of these interventions.MethodsStepping Stones and Creating Futures intervention is a participatory gender transformative and livelihoods strengthening intervention. It is being evaluated through a cluster randomized control trial amongst young women and men (18–30) living in urban informal settlements in eThekwini Municipality, South Africa. The evaluation includes a qualitative process evaluation and cost-effectiveness analysis. A comparison of baseline characteristics of participants is also included.DiscussionThis is one of the first large trials to prevent IPV and HIV-vulnerability amongst young women and men in urban informal settlements. Given the mixed methods evaluation, the results of this trial have the ability to develop a stronger understanding of what works to prevent violence against women and the processes of change in interventions.Trial registrationNCT03022370. Registered 13 January 2017, retrospectively registered.

This paper seeks to refocus debates on structural interventions away from ‘assessing’ their effectiveness towards understanding processes around how such interventions are implemented. Implementation Science is focused on understanding potential challenges of translating interventions from highly controlled conditions into ‘real life’ settings. Using the case study of Stepping Stones and Creating Futures a structural and behavioural intervention to reduce intimate partner violence and HIV risk behaviours amongst young women and men in urban informal settlements, we explore the challenges of implementing such an approach. We move beyond simply describing challenges of implementing, to understand how these challenges had an impact on the safe social space the intervention seeks to create as its underlying theory of change. We identify four major challenges of implementation: taxi fares, food provided during the intervention, young people’s ongoing need to work and journals provided during the intervention. We suggest that, in different ways, these factors all impinged on the emergence of a safe social space. Understanding the challenges of implementing the intervention is critical for reflecting on scaling up interventions. Central to this is the need to work with participants to help them negotiate the challenges of participating in interventions.