Early Intervention for Children at High Risk of Developmental Disability in Low- and Middle-Income Countries:A Narrative Review

In low- and middle-income countries (LMICs), while neonatal mortality has fallen, the number of children under five with developmental disability remains unchanged. The first thousand days are a critical window for brain development, when interventions are particularly effective. Early Childhood Interventions (ECI) are supported by scientific, human rights, human capital and programmatic rationales. In high-income countries, it is recommended that ECI for high-risk infants start in the neonatal period, and specialised interventions for children with developmental disabilities as early as three months of age; more data is needed on the timing of ECI in LMICs. Emerging evidence supports community-based ECI which focus on peer support, responsive caregiving and preventing secondary morbidities. A combination of individual home visits and community-based groups are likely the best strategy for the delivery of ECI, but more evidence is needed to form strong recommendations, particularly on the dosage of interventions. More data on content, impact and implementation of ECI in LMICs for high-risk infants are urgently needed. The development of ECI for high-risk groups will build on universal early child development best practice but will likely require tailoring to local contexts

Maternal experiences of caring for an infant with neurological impairment after neonatal encephalopathy in Uganda: a qualitative study

Purpose: The study investigated maternal experiences of caring for a child affected by neurological impairment after neonatal encephalopathy (NE) (“birth asphyxia”) in Uganda. Methods: Between September 2011 and October 2012 small group and one-on-one in-depths interviews were conducted with mothers recruited to the ABAaNA study examining outcomes from NE in Mulago hospital, Kampala. Data were analysed thematically with the aid of Nvivo 8 software. Findings: Mothers reported caring for an infant with impairment was often complicated by substantial social, emotional and financial difficulties and stigma. High levels of emotional distress, feelings of social isolation and fearfulness about the future were described. Maternal health-seeking ability was exacerbated by high transport costs, lack of paternal support and poor availability of rehabilitation and counselling services. Meeting and sharing experiences with similarly affected mothers was associated with more positive maternal caring experiences. Conclusion: Mothering a child with neurological impairment after NE is emotionally, physically and financially challenging but this may be partly mitigated by good social support and opportunities to share caring experiences with similarly affected mothers. A facilitated, participatory, community-based approach to rehabilitation training may have important impacts on maximising participation and improving the quality of life of affected mothers and infants. Implications for Rehabilitation Caring for an infant with neurological impairment after NE in Uganda has substantial emotional, social and financial impacts on families and is associated with high levels of emotional stress, feelings of isolation and stigma amongst mothers. Improved social support and the opportunity to share experiences with other similarly affected mothers are associated with a more positive maternal caring experience. High transport costs, lack of paternal support and poor availability of counselling and support services were barriers to maternal healthcare seeking. Studies examining the feasibility, acceptability and impact of early intervention programmes are warranted to maximise participation and improve the quality of life for affected mothers and their infants

Comparison of β-Hydroxylase Enzyme 11 Serum in Obese, Overweight, and Normoweight Young Men

Background: Previous studies showed that cardiovascular risk factor was increased in obese and overweight subjects. Obesity and cardiovascular risk factor are associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that causes hypercortisolism, cortisol level is associated with cardiovascular risk factor on obesity. 11 β-hydroxylase is an enzyme that involved in cortisol synthesis. The aim of this study was to investigate 11 β-Hydroxylase concentration in obesity, overweight, and normal weight young men.Subjects and Method: This was analytic-observational study using cross-sectional design. The study was conducted at HKBP Nommensen University, Medan. The study subjects included by 76 young men aged 18-28 years old, consisting of 25 obese subjects, 25 overweight, and 25 normoweight. The concentration of 11 β-Hydroxylase was evaluated in blood sample after 10 hours fasting. The data was analyzed bivariately.Results: Mean of 11 β-Hydroxylase concentration was 52.76 ± 44.27 in obese subjects, 70.16 ± 46.83 in overweight subjects, and 43.42 ± 27.75 in normoweight subjects. The 11 β-Hydroxylase concentration in overweight subjects was statistically higher than normoweight subjects (p = 0.007), but the 11 β-Hydroxylase concentration on obese subjects statistically was not different from normoweight subjects (p = 0.362).Conclusion: The 11 β-Hydroxylase concentration on overweight subject is higher than normoweight subject. There is no difference of 11 β-Hydroxylase concentration on obese and normoweight subject. Mitochondrial stress and mitochondrial failure mechanism on overweight and obesity merit further investigation

Maternal experiences of caring for an infant with neurological impairment after neonatal encephalopathy in Uganda: a qualitative study.

PURPOSE: The study investigated maternal experiences of caring for a child affected by neurological impairment after neonatal encephalopathy (NE) ("birth asphyxia") in Uganda. METHODS: Between September 2011 and October 2012 small group and one-on-one in-depths interviews were conducted with mothers recruited to the ABAaNA study examining outcomes from NE in Mulago hospital, Kampala. Data were analysed thematically with the aid of Nvivo 8 software. FINDINGS: Mothers reported caring for an infant with impairment was often complicated by substantial social, emotional and financial difficulties and stigma. High levels of emotional distress, feelings of social isolation and fearfulness about the future were described. Maternal health-seeking ability was exacerbated by high transport costs, lack of paternal support and poor availability of rehabilitation and counselling services. Meeting and sharing experiences with similarly affected mothers was associated with more positive maternal caring experiences. CONCLUSION: Mothering a child with neurological impairment after NE is emotionally, physically and financially challenging but this may be partly mitigated by good social support and opportunities to share caring experiences with similarly affected mothers. A facilitated, participatory, community-based approach to rehabilitation training may have important impacts on maximising participation and improving the quality of life of affected mothers and infants. Implications for Rehabilitation Caring for an infant with neurological impairment after NE in Uganda has substantial emotional, social and financial impacts on families and is associated with high levels of emotional stress, feelings of isolation and stigma amongst mothers. Improved social support and the opportunity to share experiences with other similarly affected mothers are associated with a more positive maternal caring experience. High transport costs, lack of paternal support and poor availability of counselling and support services were barriers to maternal healthcare seeking. Studies examining the feasibility, acceptability and impact of early intervention programmes are warranted to maximise participation and improve the quality of life for affected mothers and their infants

Mid-upper arm circumference (MUAC) measurement usage among children with disabilities: A systematic review

Background: Anthropometric measurements, including mid-upper arm circumference (MUAC), are used for monitoring and evaluating children's nutritional status. Evidence is limited on optimal nutritional assessment for children with disabilities, who are at high risk for malnutrition. Aim: This study describes MUAC use among children with disabilities. Methods: Four databases (Embase, Global Health, Medline, and CINHAL) were searched from January 1990 through September 2021 using a predefined search strategy. Of the 305 publications screened, 32 papers were included. Data included children 6 months to 18 years old with disabilities. Data including general study characteristics, methods for MUAC measurement, terminology, and measurement references were extracted into Excel. Due to heterogeneity of the data, a narrative synthesis was used. Results: Studies from 24 countries indicate that MUAC is being used as part of nutritional assessment, but MUAC measurement methods, references, and cutoffs were inconsistent. Sixteen (50%) reported MUAC as a mean ± standard deviation (SD), 11 (34%) reported ranges or percentiles, 6 (19%) reported z-scores, and 4 (13%) used other methods. Fourteen (45%) studies included both MUAC and weight-for-height but nonstandard reporting limited comparability of the indicators for identifying those at risk of malnutrition. Conclusion: Although its speed, simplicity, and ease of use afford MUAC great potential for assessing children with disabilities, more research is needed to understand its appropriateness, and how it performs at identifying nutritionally high-risk children in comparison to other measures. Without validated inclusive measures to identify malnutrition and monitor growth and health, millions of children could have severe consequences for their development

Evaluation of 11C-Acetate and 18 F-FDG PET/CT in mouse multidrug resistance gene-2 deficient mouse model of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) remains a global health problem with unique diagnostic and therapeutic challenges, including difficulties in identifying the highest risk patients. Previous work from our lab has established the murine multidrug resistance-2 mouse (MDR2) model of HCC as a reasonable preclinical model that parallels the changes seen in human inflammatory associated HCC. The purpose of this study is to evaluate modalities of PET/CT in MDR2−/− mice in order to facilitate therapeutic translational studies from bench to bedside. Methods 18F-FDG and 11C-acetate PET/CT was performed on 12 m MDR2−/− mice (n = 3/tracer) with HCC and 12 m MDR2−/+ control mice (n = 3/tracer) without HCC. To compare PET/CT to biological markers of HCC and cellular function, serum alpha-fetoprotein (AFP), lysophosphatidic acid (LPA), cAMP and hepatic tumor necrosis factor α (TNFα) were quantified in 3-12 m MDR2−/− (n = 10) mice using commercially available ELISA analysis. To translate results in mice to patients 11C-acetate PET/CT was also performed in 8 patents suspected of HCC recurrence following treatment and currently on the liver transplant wait list. Results Hepatic18F-FDG metabolism was not significantly increased in MDR2−/− mice. In contrast, hepatic 11C-acetate metabolism was significantly elevated in MDR2−/− mice when compared to MDR2−/+ controls. Serum AFP and LPA levels increased in MDR2−/− mice contemporaneous with the emergence of HCC. This was accompanied by a significant decrease in serum cAMP levels and an increase in hepatic TNFα. In patients suspected of HCC recurrence there were 5 true positives, 2 true negatives and 1 suspected false 11C-acetate negative. Conclusions Hepatic 11C-acetate PET/CT tracks well with HCC in MDR2−/− mice and patients with underlying liver disease. Consequently 11C-acetate PET/CT is well suited to study 1) HCC emergence/progression in patients and 2) reduce animal numbers required to study new chemotherapeutics in murine models of HCC

Protocol for a randomised trial of early kangaroo mother care compared to standard care on survival of pre-stabilised preterm neonates in The Gambia (eKMC).

BACKGROUND: Complications of preterm birth cause more than 1 million deaths each year, mostly within the first day after birth (47%) and before full post-natal stabilisation. Kangaroo mother care (KMC), provided as continuous skin-to-skin contact for 18 h per day to fully stabilised neonates ≤ 2000 g, reduces mortality by 36-51% at discharge or term-corrected age compared with incubator care. The mortality effect of starting continuous KMC before stabilisation is a priority evidence gap, which we aim to investigate in the eKMC trial, with a secondary aim of understanding mechanisms, particularly for infection prevention. METHODS: We will conduct a single-site, non-blinded, individually randomised, controlled trial comparing two parallel groups to either early (within 24 h of admission) continuous KMC or standard care on incubator or radiant heater with KMC when clinically stable at > 24 h of admission. Eligible neonates (n = 392) are hospitalised singletons or twins < 2000 g and 1-24 h old at screening who are mild to moderately unstable as per a trial definition using cardio-respiratory parameters. Randomisation is stratified by weight category (< 1200 g; ≥ 1200 g) and in random permuted blocks of varying sizes with allocation of twins to the same arm. Participants are followed up to 28 ± 5 days of age with regular inpatient assessments plus criteria-led review in the event of clinical deterioration. The primary outcome is all-cause neonatal mortality by age 28 days. Secondary outcomes include the time to death, cardio-respiratory stability, hypothermia, exclusive breastfeeding at discharge, weight gain at age 28 days, clinically suspected infection (age 3 to 28 days), intestinal carriage of extended-spectrum beta-lactamase producing (ESBL) Klebsiella pneumoniae (age 28 days), and duration of the hospital stay. Intention-to-treat analysis will be applied for all outcomes, adjusting for twin gestation. DISCUSSION: This is one of the first clinical trials to examine the KMC mortality effect in a pre-stabilised preterm population. Our findings will contribute to the global evidence base in addition to providing insights into the infection prevention mechanisms and safety of using this established intervention for the most vulnerable neonatal population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03555981. Submitted 8 May 2018 and registered 14 June 2018. Prospectively registered

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

Correction: Rating early child development outcome measurement tools for routine health programme use.

The authors would like to correct the funding statement. Currently it reads as 'Funding: This supplement has been made possible by funding support from the Bernard van Leer Foundation. Saving Brains impact and process evaluation funded by Grand Challenges Canada.' This funding statement is correct for all the other papers in the series but for this specific paper a key funder (Children's Investment Fund Foundation) was not listed, and Grand Challenges Canada should not be listed. The correct funding statement should be as follows: 'Funding: This supplement has been made possible by funding support from the Bernard van Leer Foundation (funding costs of publication and launch) and the Children's Investment Foundation Fund (partial funding of author time (DB) and (JC) and funding for EN-SMILING study)