Search

Introduction: Improving peri- and postnatal facility-based care in low-resource settings (LRS) could save over 6000 babies' lives per day. Most of the annual 2.4 million neonatal deaths and 2 million stillbirths occur in healthcare facilities in LRS and are preventable through the implementation of cost-effective, simple, evidence-based interventions. However, their implementation is challenging in healthcare systems where one in four babies admitted to neonatal units die. In high-resource settings healthcare systems strengthening is increasingly delivered via learning healthcare systems to optimise care quality, but this approach is rare in LRS. Methods: Since 2014 we have worked in Bangladesh, Malawi, Zimbabwe, and the UK to co-develop and pilot the Neotree system: an android application with accompanying data visualisation, linkage, and export. Its low-cost hardware and state-of-the-art software are used to support healthcare professionals to improve postnatal care at the bedside and to provide insights into population health trends. Here we summarise the formative conceptualisation, development, and preliminary implementation experience of the Neotree. Results: Data thus far from ~18 000 babies, 400 healthcare professionals in four hospitals (two in Zimbabwe, two in Malawi) show high acceptability, feasibility, usability, and improvements in healthcare professionals' ability to deliver newborn care. The data also highlight gaps in knowledge in newborn care and quality improvement. Implementation has been resilient and informative during external crises, for example, coronavirus disease 2019 (COVID-19) pandemic. We have demonstrated evidence of improvements in clinical care and use of data for Quality Improvement (QI) projects. Conclusion: Human-centred digital development of a QI system for newborn care has demonstrated the potential of a sustainable learning healthcare system to improve newborn care and outcomes in LRS. Pilot implementation evaluation is ongoing in three of the four aforementioned hospitals (two in Zimbabwe and one in Malawi) and a larger scale clinical cost effectiveness trial is planned.

Additional file 1: Figure S1. Participant questionnaire. Supplementary Table S1. Patient reported disease features in questionnaire responders by medication status*. Supplementary Table S2. Myositis-Specific and Myositis-Associated antibody status of questionnaire responders. Supplementary Table S3. Responses to questions regarding growth and development. Supplementary Table S4. Height, weight and BMI percentiles at diagnosis and at time of questionnaire. Supplementary Table S5. Questionnaire data regarding smoking compared to UK ONS data. Supplementary Table S6. Alcohol intake of participants compared to UK ONS data. Supplementary Table S7. Numbers with ≥ 3 longitudinal values for CMAS, MMT8, modified skin DAS and Physician Global VAS.

This paper investigates how educational and geographic capital are assorted among households in rural Nepal, and how women's marital age may shape this distribution. Our focus on the timing of marriage adds a new dimension to studies of geographies of youth and marital assortment, while our emphasis on the physical and spatial attributes of households leads us to propose the concept of geographic capital, operationalised here as agrarian landholding and access to rural markets. Using data on 17,284 women from rural lowland Nepal, heat tables showed substantial pairing among uneducated spouses, whereas educated men married women with varying levels of schooling, partly because fewer women were educated. Multivariable logistic regression models showed that the odds of marrying an educated man increased substantially for women with secondary education, and vice versa. Educated women were also more likely to marry into households with geographic capital. However, landowning husbands tended to marry younger wives, perhaps because the natal home was prepared to marry daughters earlier in order to access this geographic capital. The youngest-marrying women were least likely to marry into households with accessibility to markets. Our findings may help understand the decisions of both a woman's natal and marital household over the timing of her marriage, and the investment in her formal education. These patterns have implications for both spouses because capital not only shapes marital pairing, but also the spatial niche of the household within which women and their children will experience their life-course.

Background: Perimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research. \ud \ud Methods: Experts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish ‘agreement’. Divergence of opinions was investigated and resolved where possible through further iterations. \ud \ud Results: 7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75–7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally. Panel members highlighted the importance of informing decisions based upon individual circumstances—from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing. \ud \ud Conclusions: There is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals’ lifetime, highlighting the need for further research.

Pre-synaptic secretion of brain-derived neurotrophic factor (BDNF) from noradrenergic neurons may protect the Alzheimer's disease (AD) brain from amyloid pathology. While the BDNF polymorphism (rs6265) is associated with faster cognitive decline and increased hippocampal atrophy, a replicable genetic association of BDNF with AD risk has yet to be demonstrated. This could be due to masking by underlying epistatic interactions between BDNF and other loci that encode proteins involved in moderating BDNF secretion (DBH and Sortilin).We performed a multi-cohort case-control association study of the BDNF,DBH, and SORT1 loci comprising 5,682 controls and 2,454ADpatients from Northern Europe(87% of samples) and Spain (13%). The BDNF locus was associated with increased AD risk (odds ratios; OR= 1.1-1.2, p = 0.005-0.3), an effect size that was consistent in the Northern European (OR = 1.1-1.2, p = 0.002-0.8) but not the smaller Spanish (OR = 0.8-1.6, p = 0.4-1.0) subset. A synergistic interaction between BDNF and sex (synergy factor; SF = 1.3-1.5 p = 0.002-0.02) translated to a greater risk of AD associated with BDNF in women (OR = 1.2-1.3, p = 0.007-0.00008) than men (OR = 0.9-1.0, p = 0.3-0.6). While the DBH polymorphism (rs1611115) was also associated with increased AD risk (OR = 1.1, p = 0.04) the synergistic interaction (SF = 2.2, p = 0.007) betweenBDNF(rs6265) andDBH(rs1611115) contributed greater AD risk than either gene alone, an effect that was greater in women (SF = 2.4, p = 0.04) than men (SF = 2.0, p = 0.2). These data support a complex genetic interaction at loci encoding proteins implicated in the DBH-BDNF inflammatory pathway that modifies AD risk, particularly in women., Alzheimer’s Research UK and Alzheimer’s Society and is supported by BRACE (Bristol Research into Alzheimer’s and Care of the Elderly) and the Medical Research Council. This research benefitted from funding awarded to the NIHR Great Ormond Street Hospital Biomedical Research Centre. OB, P S-J and ER were supported by grants from, IDIVAL, Instituto de Salud Carlos III (Fondo de Investigación Sanitario) and European Funds for Regional Development (FEDER); PI15/00058, CP13/00091, PI08/0139, PI12/02288, PI16/01652, PI13/01008), JPND (DEMTEST PI11/03028 and the CIBERNED program. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE1 and 2), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012)

Pharmacodynamic (PD) count data can exhibit bimodality and nonequidispersion complicating the inclusion of drug effect. The purpose of this study was to explore four different mixture distribution models for bimodal count data by including both drug effect and distribution truncation. An example dataset, which exhibited bimodal pattern, was from rodent brief-access taste aversion (BATA) experiments to assess the bitterness of ascending concentrations of an aversive tasting drug. The two generalized Poisson mixture models performed the best and was flexible to explain both under and overdispersion. A sigmoid maximum effect (Emax ) model with logistic transformation was introduced to link the drug effect to the data partition within each distribution. Predicted density-histogram plot is suggested as a model evaluation tool due to its capability to directly compare the model predicted density with the histogram from raw data. The modeling approach presented here could form a useful strategy for modeling similar count data types.

Increasing numbers of women in resource-rich settings are prescribed zidovudine (ZDV)-sparing highly active antiretroviral therapy (HAART) in pregnancy. We compare ZDV-sparing with ZDV-containing HAART in relation to maternal viral load at delivery, mother-to-child transmission (MTCT) of HIV, and congenital abnormality. This is an analysis of data from the National Study of HIV in Pregnancy and Childhood and the European Collaborative Study. Data on 7573 singleton births to diagnosed HIV-infected women between January 2000 and June 2009 were analyzed. Logistic regression models were fitted to estimate adjusted odds ratios (AORs). Overall, 15.8% (1199 of 7573) of women received ZDV-sparing HAART, with increasing use between 2000 and 2009 (P

Background As HIV preventive efforts improve, an increasing population of preadolescent HIV-exposed but uninfected children face significant developmental and health challenges, including disclosure of parental HIV. The aim of this research is to test the efficacy of the Amagugu intervention to increase maternal HIV-disclosure to HIV-uninfected children aged 6-10 years, leading to improvements in health care engagement and custody planning. Methods Individually randomised efficacy trial in rural KwaZulu-Natal, South Africa; follow-up to nine months. We used computer-generated simple random sampling with blinded assessment. The Amagugu intervention included six home-based counselling sessions; the enhanced standard of care included one clinic-based counselling session. The primary outcome was maternal HIV-disclosure (full, partial, none) measured at 9-months using an intention to treat analysis Findings We consecutively approached 634 women at four primary health care clinics (July 2013-December 2014). 464 mothers were randomised (Amagugu intervention n=235; enhanced standard of care n=229); 428 (92%) completed the 9-month assessment (September 2015). The Amagugu intervention led to an increase in any disclosure (204/235 vs. 128/229 aOR 9.88 [5.55-17.57] p Conclusions and Relevance This trial of a psychological intervention, the first from a low-resource setting, demonstrated positive outcomes. The counsellor-driven intervention changed maternal behaviours achieving high rates of mother-led HIV disclosure, enhanced health education and custody planning. Longer term follow-up and effectiveness research is required.