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Importance There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, Setting, and Participants The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main Outcomes and Measures The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George’s Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was –124.6 mL (95% CI, −178.0 to −71.2 mL) with 600 mg of ziritaxestat vs –147.3 mL (95% CI, −199.8 to −94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, −52.3 to 97.6 mL]), and –173.9 mL (95% CI, −225.7 to −122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, −26.7 mL [95% CI, −100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was –173.8 mL (95% CI, −209.2 to −138.4 mL) with 600 mg of ziritaxestat vs –176.6 mL (95% CI, −211.4 to −141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, −46.9 to 52.4 mL]) and –174.9 mL (95% CI, −209.5 to −140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, −47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo. Conclusions and Relevance Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment. Trial Registration ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444

Background The effectiveness of insecticide-treated nets (ITNs) in preventing malaria in young children is well established. However, the long-term effects of early childhood ITN use on educational outcomes, fertility, and marriage in early adulthood are not well understood. Methods This study uses 22 years of longitudinal data from rural Tanzania to investigate the associations between early life ITN use and educational attainment, fertility and marriage in early adulthood. Unadjusted and adjusted logistic regression models were used to estimate the associations between early life ITN use and early adult outcomes (education, childbearing, and marriage), controlling for potential confounders, such as parental education, household asset quintiles, and year of birth. Analyses were conducted separately for men and women. Results A total of 6706 participants born between 1998 and 2000 were enrolled in the study between 1998 and 2003. By 2019 a total of 604 had died and a further 723 could not be found, leaving 5379 participants who were interviewed, among whom complete data were available for 5216. Among women, sleeping under a treated net at least half of the time during early childhood [“high ITN use”] was associated with a 13% increase in the odds of completing primary school (adjusted odds ratio (aOR) 1.13 [0.85, 1.50]) and with a 40% increase in the odds of completing secondary school (aOR 1.40 [1.11, 1.76]) compared with women sleeping less frequently under ITNs in early life ( Conclusion This study found that early life use of ITNs was strongly associated with increased school completion in both men and women. More marginal associations were found between early-life ITN use and both marriage and child-bearing in early adulthood. ITN use during early childhood may have long-term positive effects on educational attainment in Tanzania. However, further research is needed to understand the mechanisms behind these associations and to explore the broader impacts of ITN use on other aspects of early adult life.

IntroductionWe examine whether personality traits mediate the association between childhood adversity and educational attainment using longitudinal data from a cohort in Zambia.MethodsWe fit a structural equation model using data on three forms of childhood adversity—household poverty, stunting as a measure of chronic malnutrition, and death of a parent—and data on the “Big Five” personality traits and educational attainment assessed at 15 years of age.ResultsWe find that childhood poverty and death of a parent are associated with lower openness to experience. Furthermore, openness to experience mediates 93% of the negative association between death of a parent and school enrollment and 19% of the negative association between childhood poverty and enrollment.DiscussionOur findings reinforce a diverse and growing body of evidence linking childhood adversity to educational attainment while also placing it in a new light. Future work should continue to examine the biological and psychosocial pathways that determine openness to experience and other personality traits, as well as their role in shaping important life outcomes.

INTRODUCTION: Livestock diseases are a major constraint to agricultural productivity, frequently causing significant livelihood losses for farmers, and negatively affecting public food safety and security. Vaccines provide an effective and profitable means for controlling most infectious livestock diseases, but remain underutilized. This study sought to assess the barriers and determinants of vaccination utilization for priority livestock diseases in Ghana. METHODS: We conducted a mixed-method study involving a quantitative survey with ruminant livestock farmers (N = 350) and seven focus group discussions (FGD) involving 65 ruminant livestock farmers. The survey data were analyzed, and distribution of barriers to vaccination access described. We evaluated the determinants of vaccination utilization (any use of vaccination against contagious-bovine-pleuropneumonia (CBPP) and peste-des-petits-ruminants (PPR) in 2021) using logistic regression analyses at the 0.05 significance level. FGD transcripts were analyzed deductively. We used triangulation to achieve convergence across the different datasets and analyses. RESULTS: The farmers kept an average (median) of 5 tropical livestock units (TLUs) of ruminant livestock (IQR=2.6-12.0) that were on average 8 kilometers (IQR=1.9-12.4) away from veterinary officers (VOs). Only 16% (56/350) of herds were vaccinated against the diseases. Most farmers (274/350) had limited knowledge on vaccines against CBPP and PPR infections, 63% (222/350) perceived low risk of these diseases to their herds. About half of farmers reported experiencing outbreaks of either disease in the study year (2021). Farmers scored on average 80.5 out of 98 (IQR=74-85) on the RS-14 resilience scale. After adjusting for farmers' livestock rearing experience, herd size, sex, wealth status, distance to VOs, previous disease outbreaks, and perceived risk of the diseases, vaccination utilization was negatively associated with limited knowledge (aOR=0.19, 95%CI=0.08-0.43), and positively associated with personal exposure to outbreaks in the study year (aOR=5.26, 95%CI=2.01-13.7) and increasing resilience (aOR=1.13, 95%CI=1.07-1.19). FGDs revealed farmer misconceptions about vaccines, costs of vaccines, and timely access to vaccines from VOs as additional barriers. CONCLUSIONS: Acceptability, affordability, accessibility, and availability of vaccine services represent the main barriers to vaccines utilization by ruminant livestock farmers in Ghana. Given that limited knowledge regarding the value of vaccination and shortfalls in veterinary service supply are of central importance for both the demand and supply side, more collaboration between the different stakeholders in a transdisciplinary manner to effectively address the low vaccination utilization problem is needed.

INTRODUCTION: Early reading interventions hold promise for increasing language and literacy development in young children and improving caregiver-child interactions. To engage rural caregivers and young children in home reading, Zambian child psychologists and education specialists developed a culturally representative, local language children's book targeted at pre-grade 1 children. OBJECTIVES: We qualitatively assessed community acceptability and use of the book distributed to households with young children in two provinces of Zambia. METHODS: We conducted 15 focus group discussions (FGDs) with women (n=117) who received the "Zambian folktales adapted stories for young children" book. A codebook was created a priori, based on established themes in the guide; content analysis was conducted in Nvivo v12. Data were interpreted against the Theoretical Framework on Acceptability. FINDINGS: Respondents described wide acceptability of the children's book across multiple framework constructs. Respondents believed the book was culturally appropriate for its folktale structure and appreciated the morals and lessons provided by the stories. Respondents described using the book in multiple ways including reading in one-on-one or group settings, asking the child questions about the narrative or pictures, and providing additional commentary on the actions or figures in the pictures. Respondents believed the books were helping children grow their vocabulary and early literacy skills. The book's simple vocabulary facilitated use by less educated caregivers. The primary concern voiced was the ability of low literacy caregivers to utilize the book for reading. DISCUSSION: The children's book was widely considered acceptable by rural Zambian communities. It provided a platform for an additional method of caregiver-child interactions in these households for reading, dialogue, and oral storytelling. Shared reading experiences have potentially substantial benefits for the language development and emergent literacy of young children. Programs to develop and deliver culturally acceptable books to households with limited access should be considered by governments and funders.

BACKGROUND: Stepped and Collaborative Care Models (SCCMs) have shown potential for improving mental health care. Most SCCMs have been used in primary care settings. At the core of such models are initial psychosocial distress assessments commonly in form of patient screening. We aimed to assess the feasibility of such assessments in a general hospital setting in Switzerland. METHODS: We conducted and analyzed eighteen semi-structured interviews with nurses and physicians involved in a recent introduction of a SCCM model in a hospital setting, as part of the SomPsyNet project in Basel-Stadt. Following an implementation research approach, we used the Tailored Implementation for Chronic Diseases (TICD) framework for analysis. The TICD distinguishes seven domains: guideline factors, individual healthcare professional factors, patient factors, professional interactions, incentives and resources, capacity for organizational change, and social, political, and legal factors. Domains were split into themes and subthemes, which were used for line-by-line coding. RESULTS: Nurses and physicians reported factors belonging to all seven TICD domains. An appropriate integration of the psychosocial distress assessment into preexisting hospital processes and information technology systems was the most important facilitator. Subjectivity of the assessment, lack of awareness about the assessment, and time constraints, particularly among physicians, were factors undermining and limiting the implementation of the psychosocial distress assessment. CONCLUSIONS: Awareness raising through regular training of new employees, feedback on performance and patient benefits, and working with champions and opinion leaders can likely support a successful implementation of routine psychosocial distress assessments. Additionally, aligning psychosocial distress assessments with workflows is essential to assure the sustainability of the procedure in a working context with commonly limited time.