Amy Gray

In vitro fusion of human inguinal hernia with associated epithelial transformation.

The processus vaginalis (PV) is a peritoneal diverticulum which forms to allow descent of the fetal testis to the scrotum. During human development fusion and obliteration of the PV often fails to occur with the result that inguinal hernias are the most prevalent congenital abnormality requiring surgery in childhood. Androgen is proposed to regulate testicular descent via the genitofemoral nerve which releases the neuropeptide calcitonin gene-related peptide (CGRP). It is possible that subsequent fusion of the PV and tissue remodelling following descent is indirectly controlled by androgen via CGRP action. An organ culture assay was developed to assess fusion of the PV taken from inguinal herniotomy in infants. Fusion was induced in vitro by CGRP but not by CGRP 8–37, CGRP 27–37 or dihydrotestosterone in equimolar concentrations. Fusion was accompanied by transformation of the epithelium, as shown by staining of intermediate filament proteins, cytokeratin and vimentin. Localization studies for CGRP receptors on 25 specimens indicated CGRP acts on mesenchymal fibroblasts but not directly on PV epithelium suggesting an indirect pathway. Hepatocyte growth factor/scatter factor was found to induce fusion of PV and may be involved as an intermediate molecule in the fusion cascade. This study represents the first approach to understanding the humoral control and underlying mechanism by which the PV fuses.

Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) and are resistant to apoptosis induction.

Fas (APO-1/CD95/TNFRSF6) is a member of the tumor necrosis/nerve growth factor receptor family that signals apoptotic cell death in sensitive cells. Expression of Fas and its agonistic ligand (FasL/TNFSF6) was investigated in ex vivo pediatric brain tumor specimens of various histologic types. Fas expression was identified in all of the 18 tumors analyzed by flow cytometry and immunohistochemistry. FasL expression was identified in most of the 13 tumors analyzed by both Western analysis and immunohistochemistry. Nine of these tumor specimens were treated with either the agonistic anti-Fas antibody (APO-1) in combination with protein A or FasL in short-term cytotoxicity assays. Sensitivity to apoptosis induced by the topoisomerase II inhibitor, etoposide, was also assessed. Despite the presence of Fas, all the specimens analyzed demonstrated a high degree of resistance to Fas-mediated apoptosis. These 9 specimens also showed a high degree of resistance to etoposide. Only 2 of the 9 specimens were susceptible to etoposide-induced cell death, whereas only 3 were sensitive to Fas-mediated apoptosis. One brain tumor was sensitive to both Fas ligation and etoposide treatment. This contrasted with the high degree of susceptibility to both etoposide- and Fas-induced apoptosis observed in the reference Jurkat cell line. The results suggest that Fas expression may be a general feature of tumors of the CNS and that a significant degree of resistance to Fas-mediated apoptosis may exist in ex vivo pediatric brain tumor specimens.

Implementing WHO hospital guidelines improves quality of paediatric care in central hospitals in Lao PDR

To evaluate the impact of implementing a multifaceted intervention based on the WHO Pocketbook of Hospital Care for Children on the quality of case management of common childhood illnesses in hospitals in Lao PDR.

Providing oxygen to children in hospitals: a realist review

Abstract Objective To identify and describe interventions to improve oxygen therapy in hospitals in low-resource settings, and to determine the factors that contribute to success and failure in different contexts. Methods Using realist review methods, we scanned the literature and contacted experts in the field to identify possible mechanistic theories of how interventions to improve oxygen therapy systems might work. Then we systematically searched online databases for evaluations of improved oxygen systems in hospitals in low- or middle-income countries. We extracted data on the effectiveness, processes and underlying theory of selected projects, and used these data to test the candidate theories and identify the features of successful projects. Findings We included 20 improved oxygen therapy projects (45 papers) from 15 countries. These used various approaches to improving oxygen therapy, and reported clinical, quality of care and technical outcomes. Four effectiveness studies demonstrated positive clinical outcomes for childhood pneumonia, with large variation between programmes and hospitals. We identified factors that help or hinder success, and proposed a practical framework depicting the key requirements for hospitals to effectively provide oxygen therapy to children. To improve clinical outcomes, oxygen improvement programmes must achieve good access to oxygen and good use of oxygen, which should be facilitated by a broad quality improvement capacity, by a strong managerial and policy support and multidisciplinary teamwork. Conclusion Our findings can inform practitioners and policy-makers about how to improve oxygen therapy in low-resource settings, and may be relevant for other interventions involving the introduction of health technologies.

Improving oxygen therapy for children and neonates in secondary hospitals in Nigeria: study protocol for a stepped-wedge cluster randomised trial

BackgroundOxygen is a life-saving, essential medicine that is important for the treatment of many common childhood conditions. Improved oxygen systems can reduce childhood pneumonia mortality substantially. However, providing oxygen to children is challenging, especially in small hospitals with weak infrastructure and low human resource capacity.Methods/designThis trial will evaluate the implementation of improved oxygen systems at secondary-level hospitals in southwest Nigeria. The improved oxygen system includes: a standardised equipment package; training of clinical and technical staff; infrastructure support (including improved power supply); and quality improvement activities such as supportive supervision. Phase 1 will involve the introduction of pulse oximetry alone; phase 2 will involve the introduction of the full, improved oxygen system package. We have based the intervention design on a theory-based analysis of previous oxygen projects, and used quality improvement principles, evidence-based teaching methods, and behaviour-change strategies.We are using a stepped-wedge cluster randomised design with participating hospitals randomised to receive an improved oxygen system at 4-month steps (three hospitals per step). Our mixed-methods evaluation will evaluate effectiveness, impact, sustainability, process and fidelity. Our primary outcome measures are childhood pneumonia case fatality rate and inpatient neonatal mortality rate. Secondary outcome measures include a range of clinical, quality of care, technical, and health systems outcomes. The planned study duration is from 2015 to 2018.DiscussionOur study will provide quality evidence on the effectiveness of improved oxygen systems, and how to better implement and scale-up oxygen systems in resource-limited settings. Our results should have important implications for policy-makers, hospital administrators, and child health organisations in Africa and globally.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12617000341325. Retrospectively registered on 6 March 2017.

Improved oxygen systems in district hospitals in Lao PDR: a prospective field trial of the impact on outcomes for childhood pneumonia and equipment sustainability

Background Hypoxaemia is a common and potentially fatal complication of many childhood, newborn and maternal conditions but often not well recognised or managed in settings where resources are limited. Oxygen itself is often inaccessible due to cost or logistics. This paper describes implementation of oxygen systems in Lao district hospitals, clinical outcomes after 24 months and equipment outcomes after 40 months postimplementation. Methods A prospective field trial was conducted in 20 district hospitals, including 10 intervention hospitals that received oxygen concentrators and 10 control hospitals. Equipment outcomes were evaluated at baseline, 12, 24 and 40 months. Clinical outcomes of children under 5 years of age with pneumonia were evaluated using a before-and-after controlled study design with information retrospectively collected from medical records. Results Fourteen (37%), 7 (18%) and 12 (34%) of 38 concentrators required repair at 12, 24 and 40 months, respectively. The proportion of children discharged well increased in intervention (90% (641/712) to 95.2% (658/691)) and control hospitals (87.1% (621/713) to 92.1% (588/606)). In intervention hospitals, case fatality rates for childhood pneumonia fell from 2.7% (19/712) preintervention to 0.80% (6/691) postintervention with no change in control hospitals (1.7% (12/713) preintervention and 2.3% (14/606) postintervention). Conclusion Medium-term sustainability of oxygen concentrators in hospitals accompanied by reduced case fatality for childhood pneumonia has been demonstrated in Lao PDR. Significant local engineering capacity to address multiple causes of equipment malfunction was critical. The ongoing requirements and fragile structures within the health system remain major risks to long-term sustainability.

A Qualitative Study of Provider Perceptions of Influences on Uptake of Pediatric Hospital Guidelines in Lao PDR.

Strategies to improve the quality of hospital care are needed if ongoing gains in child health and survival are to be made. We previously reported on improvements in the quality of case management in hospitals following a guideline-based intervention in Lao PDR, with variation in the degree of change achieved between clinical conditions. This study aims to understand the factors that influenced the uptake of the guideline-based intervention, and its impact on care. This qualitative study was embedded in a mixed-methods evaluation of guideline implementation in nine hospitals in Lao PDR. Focus groups and individual interviews were conducted with 70 health staff from central, provincial, and district hospitals. The interview guide was based on the Theoretical Domains Framework. Inductive content analysis was performed on interview transcripts to identify themes, supported by field notes from the intervention. Findings were triangulated against previously reported quantitative outcomes using driver diagrams. Key influences on guidelines uptake related to the guideline and intervention (filling a void, physical accessibility, comprehensibility, training in guideline use), health staff (behavior regulation, trust in guidelines, and beliefs about consequences), and the environment (social influences particularly consensus and incorporation into clinical norms). The major barrier was family preference for treatments in conflict with guideline recommendations. This study identifies contextual factors that explain, as well as validate previously identified improvements in care following guideline implementation in Lao PDR. It provides novel understanding of why the same intervention may have a differential impact on different clinical conditions.

Opening the black box: An observational study of teaching and learning interactions for paediatrics trainees on consultant ward rounds: Understanding education on ward rounds

Ward rounds are complex activities in which education must be balanced against service. Limited evidence exists regarding how to optimise ward round education. In order to improve the educational experience, we aimed to understand the teaching and learning interactions on ward rounds with a particular focus on the experience of paediatric trainees.

Assessment of the quality of neonatal care in the Solomon Islands

To identify strengths and obstacles for improving the quality of newborn care in the Solomon Islands. Improving the quality of newborn care is a priority in the Sustainable Development Goals and the Action Plan for Healthy Newborns in the Western Pacific. The neonatal mortality rate in the Solomon Islands, a lower‐middle‐income country, has improved slower than overall child mortality. In 2013, neonatal mortality (13.2/1000) constituted 44% of under‐5 deaths (30.1/1000).

Hyponatraemia in a Lao paediatric intensive care unit: Prevalence, associations and intravenous fluid use: Hyponatraemia in intensive care in Laos

Hyponatraemia is a common and potentially deadly complication affecting hospitalised children world‐wide. Hypotonic intravenous fluids can be a significant exacerbating factor. Exclusive use of isotonic fluids, coupled with rigorous blood monitoring, has proven effective in reducing hyponatraemia in developed settings. In developing countries, where hyponatraemia is often more common and severe, different factors may contribute to its incidence and detection. We aimed to determine the prevalence and disease associations of hyponatraemia and describe the intravenous maintenance fluid prescribing practices in a Lao paediatric intensive care unit.