Increased utilisation and quality: a focus on inequality and a learning health system approach-explaining Nepal's success in reducing maternal and newborn mortality 2000-2020.

INTRODUCTION: Maternal mortality in Nepal dropped from 553 to 186 per 100 000 live births during 2000-2017 (66% decline). Neonatal mortality dropped from 40 to 21 per 1000 live births during 2000-2018 (48% decline). Stillbirths dropped from 28 to 18 per 1000 births during 2000-2019 (34% decline). Nepal outperformed other countries in these mortality improvements when adjusted for economic growth, making Nepal a 'success'. Our study describes mechanisms which contributed to these achievements. METHODS: A mixed-method case study was used to identify drivers of mortality decline. Methods used included a literature review, key-informant interviews, focus-group discussions, secondary analysis of datasets, and validation workshops. RESULTS: Despite geographical challenges and periods of political instability, Nepal massively increased the percentage of women delivering in health facilities with skilled birth attendance between 2000 and 2019. Although challenges remain, there was also evidence in improved quality and equity-of-access to antenatal care and childbirth services. The study found policymaking and implementation processes were adaptive, evidence-informed, made use of data and research, and involved participants inside and outside government. There was a consistent focus on reducing inequalities. CONCLUSION: Policies and programmes Nepal implemented between 2000 and 2020 to improve maternal and newborn health outcomes were not unique. In this paper, we argue that Nepal was able to move rapidly from stage 2 to stage 3 in the mortality transition framework not because of what they did, but how they did it. Despite its achievements, Nepal still faces many challenges in ensuring equal access to quality-care for all women and newborns.

Evolving narratives on signal functions for monitoring maternal and newborn health services: A meta-narrative inspired review.

Emergency obstetric care (EmOC) signal functions are a shortlist of key clinical interventions capable of averting deaths from the five main direct causes of maternal mortality; they have been used since 1997 as a part of an EmOC monitoring framework to track the availability of EmOC services in low- and middle-income settings. Their widespread use and proposed adaptation to include other types of care, such as care for newborns, is testimony to their legacy as part of the measurement architecture within reproductive health. Yet, much has changed in the landscape of maternal and newborn health (MNH) since the initial introduction of EmOC signal functions. As part of a project to revise the EmOC monitoring framework, we carried out a meta-narrative inspired review to reflect on how signal functions have been developed and conceptualised over the past two decades, and how different narratives, which have emerged alongside the evolving MNH landscape, have played a role in the conceptualisation of the signal function measurement. We identified three overarching narrative traditions: 1) clinical 2) health systems and 3) human rights, that dominated the discourse and critique around the use of signal functions. Through an iterative synthesis process including 19 final articles selected for the review, we explored patterns of conciliation and areas of contradiction between the three narrative traditions. We summarised five meta-themes around the use of signal functions: i) framing the boundaries; ii) moving beyond clinical capability; iii) capturing the woods versus the trees; iv) grouping signal functions and v) measurement challenges. We intend for this review to contribute to a better understanding of the discourses around signal functions, and to provide insight for the future roles of this monitoring approach for emergency obstetric and newborn care.

Immune infiltration, aggressive pathology, and poor survival outcomes in RECQL helicase deficient breast cancers.

RECQL is essential for genomic stability. Here, we evaluated RECQL in 449 pure ductal carcinomas in situ (DCIS), 152 DCIS components of mixed DCIS/invasive breast cancer (IBC) tumors, 157 IBC components of mixed DCIS/IBC and 50 normal epithelial terminal ductal lobular units (TDLUs). In 726 IBCs, CD8+, FOXP3+, IL17+, PDL1+, PD1+ T-cell infiltration (TILs) were investigated in RECQL deficient and proficient cancers. Tumor mutation burden (TMB) was evaluated in five RECQL germ-line mutation carriers with IBC by genome sequencing. Compared with normal epithelial cells, a striking reduction in nuclear RECQL in DCIS was evident with aggressive pathology and poor survival. In RECQL deficient IBCs, CD8+, FOXP3+, IL17+ or PDL1+ TILs were linked with aggressive pathology and shorter survival. In germline RECQL mutation carriers, increased TMB was observed in 4/5 tumors. We conclude that RECQL loss is an early event in breast cancer and promote immune cell infiltration.