Development and validation of a simplified score to predict neonatal mortality risk among neonates weighing 2000 g or less (NMR-2000): an analysis using data from the UK and The Gambia.

BACKGROUND: 78% of neonatal deaths occur in sub-Saharan Africa and southern Asia, among which, more than 80% are in low birthweight babies. Existing neonatal mortality risk scores have primarily been developed for high-resource settings. The aim of this study was to develop and validate a score that is practicable for low-income and middle-income countries to predict in-hospital mortality among neonates born weighing 2000 g or less using datasets from the UK and The Gambia. METHODS: This analysis used retrospective data held in the UK National Neonatal Research Database from 187 neonatal units, and data from the Edward Francis Small Teaching Hospital (EFSTH), Banjul, The Gambia. In the UK dataset, neonates were excluded if birthweight was more than 2000 g; if the neonate was admitted aged more than 6 h or following discharge; if the neonate was stillborn; if the neonate died in delivery room; or if they were moribund on admission. The Gambian dataset included all neonates weighing less than 2000 g who were admitted between May 1, 2018, and Sept 30, 2019, who were screened for but not enrolled in the Early Kangaroo Mother Care Trial. 18 studies were reviewed to generate a list of 84 potential parameters. We derived a model to score in-hospital neonatal mortality risk using data from 55 029 admissions to a random sample of neonatal units in England and Wales from Jan 1, 2010, to Dec 31, 2016. All candidate variables were included in a complete multivariable model, which was progressively simplified using reverse stepwise selection. We validated the new score (NMR-2000) on 40 329 admissions to the remaining units between the same dates and 14 818 admissions to all units from Jan 1, to Dec 31, 2017. We also validated the score on 550 neonates admitted to the EFSTH in The Gambia. FINDINGS: 18 candidate variables were selected for inclusion in the modelling process. The final model included three parameters: birthweight, admission oxygen saturation, and highest level of respiratory support within 24 h of birth. NMR-2000 had very good discrimination and goodness-of-fit across the UK samples, with a c-index of 0·8859-0·8930 and a Brier score of 0·0232-0·0271. Among Gambian neonates, the model had a c-index of 0·8170 and a Brier score of 0·1688. Predictive ability of the simplified integer score was similar to the model using regression coefficients, with c-indices of 0·8903 in the UK full validation sample and 0·8082 in the Gambian validation sample. INTERPRETATION: NMR-2000 is a validated mortality risk score for hospitalised neonates weighing 2000 g or less in settings where pulse oximetry is available. The score is accurate and simplified for bedside use. NMR-2000 requires further validation using a larger dataset from low-income and middle-income countries but has the potential to improve individual and population-level neonatal care resource allocation. FUNDING: Bill & Melinda Gates Foundation; Eunice Kennedy Shriver National Institute of Child Health & Human Development; Wellcome Trust; and Joint Global Health Trials scheme of Department of Health and Social Care, Department for International Development, Medical Research Council, and Wellcome Trust

Cosmological spacetimes balanced by a scale covariant scalar field

A scale invariant, Weyl geometric, Lagrangian approach to cosmology is explored, with a a scalar field phi of (scale) weight -1 as a crucial ingredient besides classical matter \cite{Tann:Diss,Drechsler:Higgs}. For a particularly simple class of Weyl geometric models (called {\em Einstein-Weyl universes}) the Klein-Gordon equation for phi is explicitly solvable. In this case the energy-stress tensor of the scalar field consists of a vacuum-like term Lambda g_{mu nu} with variable coefficient Lambda, depending on matter density and spacetime geometry, and of a dark matter like term. Under certain assumptions on parameter constellations, the energy-stress tensor of the phi-field keeps Einstein-Weyl universes in locally stable equilibrium. A short glance at observational data, in particular supernovae Ia (Riess ea 2007), shows interesting empirical properties of these models.Comment: 28 pages, 1 figure, accepted by Foundations of Physic

Which doctors and with what problems contact a specialist service for doctors? A cross sectional investigation

Background: In the United Kingdom, specialist treatment and intervention services for doctors are underdeveloped. The MedNet programme, created in 1997 and funded by the London Deanery, aims to fill this gap by providing a self-referral, face-to-face, psychotherapeutic assessment service for doctors in London and South-East England. MedNet was designed to be a low-threshold service, targeting doctors without formal psychiatric problems. The aim of this study was to delineate the characteristics of doctors utilising the service, to describe their psychological morbidity, and to determine if early intervention is achieved. Methods: A cross-sectional study including all consecutive self-referred doctors (n = 121, 50% male) presenting in 2002–2004 was conducted. Measures included standardised and bespoke questionnaires both self-report and clinician completed. The multi-dimensional evaluation included: demographics, CORE (CORE-OM, CORE-Workplace and CORE-A) an instrument designed to evaluate the psychological difficulties of patients referred to outpatient services, Brief Symptom Inventory to quantify caseness and formal psychiatric illness, and Maslach Burnout Inventory. Results: The most prevalent presenting problems included depression, anxiety, interpersonal, self-esteem and work-related issues. However, only 9% of the cohort were identified as severely distressed psychiatrically using this measure. In approximately 50% of the sample, problems first presented in the preceding year. About 25% were on sick leave at the time of consultation, while 50% took little or no leave in the prior 12 months. A total of 42% were considered to be at some risk of suicide, with more than 25% considered to have a moderate to severe risk. There were no significant gender differences in type of morbidity, severity or days off sick. Conclusion: Doctors displayed high levels of distress as reflected in the significant proportion of those who were at some risk of suicide; however, low rates of severe psychiatric illness were detected. These findings suggest that MedNet clients represent both ends of the spectrum of severity, enabling early clinical engagement for a significant proportion of cases that is of importance both in terms of personal health and protecting patient care, and providing a timely intervention for those who are at risk, a group for whom rapid intervention services are in need and an area that requires further investigation in the UK

Community-based family and carer-support programmes for children with disabilities

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordChildren and young people (CYP) with disabilities face multiple challenges and unmet health needs. There is considerable variability in quality of health services across the UK for these children. Families report that they experience lack of information or misinformation about health, social care and education of their child. They also highlight a desire to engage with other families of CYP with disabilities. There is growing evidence that community-based group interventions in under-resourced settings are effective at improving quality of life for both CYP with disabilities and caregivers. Few similar interventions or evidence exists in the UK. This article provides an overview of relevant evidence and, using cerebral palsy as an exemplar, discusses the potential for group-based programmes for parent carers in the UK. Groups would aim to address information needs, support providers to deliver evidence-based care, and thereby improve the health and wellbeing of CYP with disabilities

Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

Acute LPS sensitization and continuous infusion exacerbates hypoxic brain injury in a piglet model of neonatal encephalopathy

Co-existing infection/inflammation and birth asphyxia potentiate the risk of developing neonatal encephalopathy (NE) and adverse outcome. In a newborn piglet model we assessed the effect of E. coli lipopolysaccharide (LPS) infusion started 4 h prior to and continued for 48 h after hypoxia on brain cell death and systemic haematological changes compared to LPS and hypoxia alone. LPS sensitized hypoxia resulted in an increase in mortality and in brain cell death (TUNEL positive cells) throughout the whole brain, and in the internal capsule, periventricular white matter and sensorimotor cortex. LPS alone did not increase brain cell death at 48 h, despite evidence of neuroinflammation, including the greatest increases in microglial proliferation, reactive astrocytosis and cleavage of caspase-3. LPS exposure caused splenic hypertrophy and platelet count suppression. The combination of LPS and hypoxia resulted in the highest and most sustained systemic white cell count increase. These findings highlight the significant contribution of acute inflammation sensitization prior to an asphyxial insult on NE illness severity

Protocol for the Birth Asphyxia in African Newborns (Baby BRAiN) Study: a Neonatal Encephalopathy Feasibility Cohort Study

BACKGROUND: Neonatal encephalopathy (NE) is a leading cause of child mortality worldwide and contributes substantially to stillbirths and long-term disability. Ninety-nine percent of deaths from NE occur in low-and-middle-income countries (LMICs). Whilst therapeutic hypothermia significantly improves outcomes in high-income countries, its safety and effectiveness in diverse LMIC contexts remains debated. Important differences in the aetiology, nature and timing of neonatal brain injury likely influence the effectiveness of postnatal interventions, including therapeutic hypothermia. METHODS: This is a prospective pilot feasibility cohort study of neonates with NE conducted at Kawempe National Referral Hospital, Kampala, Uganda. Neurological investigations include continuous video electroencephalography (EEG) (days 1-4), serial cranial ultrasound imaging, and neonatal brain Magnetic Resonance Imaging and Spectroscopy (MRI/ MRS) (day 10-14). Neurodevelopmental follow-up will be continued to 18-24 months of age including Prechtl’s Assessment of General Movements, Bayley Scales of Infant Development, and a formal scored neurological examination. The primary outcome will be death and moderate-severe neurodevelopmental impairment at 18-24 months. Findings will be used to inform explorative science and larger trials, aiming to develop urgently needed neuroprotective and neurorestorative interventions for NE applicable for use in diverse settings. DISCUSSION: The primary aims of the study are to assess the feasibility of establishing a facility-based cohort of children with NE in Uganda, to enhance our understanding of NE in a low-resource sub-Saharan African setting and provide infrastructure to conduct high-quality research on neuroprotective/ neurorestorative strategies to reduce death and disability from NE. Specific objectives are to establish a NE cohort, in order to 1) investigate the clinical course, aetiology, nature and timing of perinatal brain injury; 2) describe electrographic activity and quantify seizure burden and the relationship with adverse outcomes, and; 3) develop capacity for neonatal brain MRI/S and examine associations with early neurodevelopmental outcomes

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries.

Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations