Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

Scaling up task-sharing psychological interventions for refugees in Jordan: a qualitative study on the potential barriers and facilitators.

Training nonspecialists in providing evidence-based psychological interventions (i.e. task-sharing) can effectively increase community access to psychological support. However, task-sharing interventions for this purpose are rarely used at scale. The aim of this study was to examine the factors influencing the potential for scaling up (i.e. scalability) of a task-sharing psychological intervention called Problem Management Plus (PM+) for Syrian refugees in Jordan. Semi-structured individual (n = 17) and group interviews (n = 20) were conducted with stakeholders knowledgeable about PM+ and the mental health system for Syrian refugees in Jordan. Using 'system innovation perspective', this study conceptualized the context as landscape developments, and systemic considerations were divided into culture (shared ways of thinking) and structure (ways of organizing). Political momentum was identified as a landscape trend likely facilitating scaling up, while predicted reductions in financial aid was regarded as a constraint. In terms of culture, the medicalized approach to mental health, stigma and gender were reported barriers for scaling up PM+. Using non-stigmatizing language and offering different modalities, childcare options and sessions outside of working hours were suggestions to reduce stigma, accommodate individual preferences and increase the demand for PM+. In relation to structure, the feasibility of scaling up PM+ largely depends on the ability to overcome legal barriers, limitations in human and financial resources and organizational challenges. We recommend sustainable funding to be made available for staff, training, supervision, infrastructure, coordination, expansion and evaluation of 'actual' scaling up of PM+. Future research may examine the local feasibility of various funding, training and supervision models. Lessons learned from actual scaling up of PM+ and similar task-sharing approaches need to be widely shared.

End-of-life care over four decades in a quaternary neonatal intensive care unit.

AIM: Death in the neonatal intensive care unit (NICU) commonly follows a decision to withdraw or limit life-sustaining treatment. Advances in medicine have changed the nature of life-sustaining interventions available and the potential prognosis for many newborn conditions. We aimed to assess changes in causes of death and end-of-life care over nearly four decades. METHODS: A retrospective review of infants dying in the NICU was performed (2017-2020) and compared with previous audits performed in the same centre (1985-1987 and 1999-2001). Diagnoses at death were recorded for each infant as well as their apparent prognosis and any withdrawal or limitations of medical treatment. RESULTS: In the recent epoch, there were 88 deaths out of 2084 admissions (4.2%), a reduction from the previous epochs (132/1362 (9.7%) and 111/1776 (6.2%), respectively, for epochs 1 and 2). More than 90% of infants died after withdrawal of life-sustaining treatment, an increase from the previous two epochs (75%). There was a reduction in deaths from chromosomal abnormalities, complications related to prematurity and severe birth asphyxia. CONCLUSIONS: There continue to be changes in both the diagnoses leading to death and approaches to withdrawal of treatment in the NICU. These may reflect ongoing changes in both prenatal and post-natal diagnostics as well as changing attitudes towards palliative care within the medical and wider community.