Prevalence and pattern of retinopathy of prematurity at two national referral hospitals in Uganda: a cross-sectional study.

BACKGROUND: Retinopathy of prematurity (ROP) is a leading cause of blindness in children and an ROP epidemic is predicted this decade in sub-Saharan Africa. With the increasing survival rate of preterm babies in Uganda, and no data on ROP prevalence, there is a need to assess the burden of ROP to inform preventive strategies and targeted screening. METHODS: We conducted a two-center cross-sectional study of preterm (< 37 weeks gestational age) infants from the neonatal units of Kawempe National Referral Hospital (KNRH) and Mulago Specialised Women and Neonatal Hospital (MSWNH) from August 2022 to October 2022. An ophthalmologist examined all participants using an indirect ophthalmoscope with a + 20D convex lens and captured digital images using a Volk iNview™ Fundus Camera. The collected data were entered into Epidata 4.2 and exported to Stata 14.0 for analysis. RESULTS: 331 preterm infants enrolled in this study. The oxygen received was unblended. The mean gestational age was 30.4 ± 2.7 weeks, and the mean birth weight was 1597 ± 509 g. 18/101 (17.8%) were found to have any ROP amongst the preterm infants recruited from MSWNH, 1/230 (0.4%) from KNRH [95% CI] had any stage of ROP (i.e. stage 5). Of these, 8 (42.1%) had stage 2 ROP. Infants with a birth weight below 1500 g were 10 times more likely to have ROP than those among infants with a birth weight more than 1500 g [AOR: 10.07 (2.71-37.44)]. Infants who were not fed exclusively on breast milk had higher odds of having ROP than those exclusively fed on breast milk [AOR: 7.82(1.92-31.82)]. CONCLUSION: 6% of preterm infants born in two tertiary hospitals in Uganda were found to have ROP. Lack of exclusive feeding on breast milk and birth weight of less than 1500 g were strong predictors of ROP. The higher prevalence of ROP in MSWNH calls for cautious use of oxygen among preterms. We recommend targeted ROP screening for those at risk.

Oxygen systems to improve clinical care and outcomes for children and neonates: A stepped-wedge cluster-randomised trial in Nigeria.

BACKGROUND: Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. METHODS AND FINDINGS: We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77-1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50-2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04-2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76-2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12-0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60-1.58, p = 0.913; aOR 1.12, 95% CI 0.56-2.26, p = 0.762; aOR 0.90, 95% CI 0.57-1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016-2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes. CONCLUSIONS: We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000341325.

Supporting caregivers of children living with disability in a humanitarian context: realist-informed evaluation of the 'Mighty Children' programme in Afghanistan.

INTRODUCTION: To ensure that humanitarian action is disability-inclusive, evidence is needed to understand how different strategies to support children living with disabilities and their families can work in these settings. Evidence from other contexts suggests support groups can improve caregiver quality of life (QOL). This study reports an evaluation of the 'Mighty Children' programme a participatory educational support group programme for caregivers of children living with disability in Kabul province, Afghanistan. METHODS: We conducted a mixed-methods realist-informed before-and-after study to measure change in caregiver-reported QOL and explore how and for whom the programme worked, and in what contexts. Female caregivers of children with any disability were recruited through clinics in urban Kabul (n=3) and rural Paghman district (n=3). We collected quantitative data on QOL pre/post programme using the Paediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM). Qualitative data were collected through facilitator and participant focus groups postprogramme. RESULTS: 118 caregivers participated in two cohorts (November 2020, February 2021). Caregivers expressed a significant increase in QOL from baseline to programme completion (t(125)=-10.7, p≤0.0001). Participation in cohort 2 was associated with the greatest PedsQL-FIM change.Qualitative data revealed positive changes postprogramme in five key areas: caregiver mindset, parenting practices, disability-inclusive behaviours, psychological well-being and child functioning. These changes were seen as both outcomes and mechanisms influencing the primary outcome of QOL. Mechanisms that mediated these changes included increased knowledge of disability and the core acceptance and commitment therapy components of mindfulness and acceptance. CONCLUSION: The Mighty Children caregiver support programme for children living with disability in Afghanistan was associated with improved caregiver QOL. Further studies are warranted to explore pathways to scale, sustainability and potential application in other settings.

Improving effective coverage of medical-oxygen services for neonates and children in health facilities in Uganda: a before-after intervention study.

BACKGROUND: Medical oxygen services are essential for the care of acutely unwell patients. We aimed to assess the effects of a multilevel, multicomponent health-system intervention on hypoxaemia detection, oxygen therapy, and mortality among neonates and children attending level IV health centres and hospitals in Uganda. METHODS: For this before-after intervention study, we included children who attended paediatric or neonatal wards of 24 level IV health centres and seven general or regional referral hospitals in the Busoga and North Buganda regions of Uganda between June 1, 2020, and June 30, 2022. All neonates younger than 1 month and children aged 1 month to 14 years were eligible for inclusion. We excluded neonates who were not sick but stayed in the maternity ward for routine postnatal care. The intervention involved clinical training, mentorship, and supportive supervision; provision of pulse oximeters and cylinder-based oxygen sources; biomedical-capacity support; and support to develop and disseminate oxygen supply strategies, oxygen therapy guidelines, and lists of essential oxygen supplies. Trained research assistants extracted individual patient data from case notes using a standardised electronic data collection form. Data were collected on health-facility details, age, sex, clinical signs and symptoms, admission diagnoses, pulse oximetry readings, oxygen therapy details, and final patient outcome. The primary outcome was the proportion of admitted neonates and children with a pulse oximetry oxygen saturation reading documented in their patient case notes on day 1 of health-facility admission (ie, pulse oximetry coverage). We used mixed-effects logistic regression to evaluate the effect of the intervention. FINDINGS: We obtained data on 71 997 eligible neonates and children admitted to 31 participating health facilities; the primary analysis included 10 001 patients in the pre-intervention period (ie, June 1 to Oct 30, 2020) and 51 329 patients in the post-intervention period (ie, March 1, 2021, to June 30, 2022). Because 1356 patients had missing data for sex, 4365 (46·7%) of 9347 in the pre-intervention group and 22 831 (46·2%) of 49 410 in the post-intervention group were female; 4982 (53·3%) in the pre-intervention group and 26 579 (53·8%) in the post-intervention group were male. The proportion of neonates and children with pulse oximetry at admission increased from 2365 (23·7%) of 10 001 in the pre-intervention period to 45 029 (87·7%) of 51 328 in the post-intervention period. Adjusted analysis indicated greater likelihood of a patient receiving pulse oximetry during the post-intervention period compared with the pre-intervention period (adjusted odds ratio 40·10, 95% CI 37·38-42·93; p<0·0001). INTERPRETATION: Large-scale improvements in hospital oxygen services are achievable and have the potential to improve clinical outcomes. Governments should be encouraged to develop national oxygen plans and focus investment on interventions that have been shown to be effective, including the introduction of pulse oximetry into routine hospital care and clinical and biomedical mentoring and support. FUNDING: Bill & Melinda Gates Foundation and ELMA Philanthropies. TRANSLATIONS: For the Luganda and Lusoga translations of the abstract see Supplementary Materials section.

'Let him die in peace': understanding caregiver's refusal of medical oxygen treatment for children in Nigeria.

INTRODUCTION: Efforts to improve oxygen access have focused mainly on the supply side, but it is important to understand demand barriers, such as oxygen refusal among caregivers. We therefore aimed to understand caregiver, community and healthcare provider (HCP) perspectives and experiences of medical oxygen treatments and how these shape oxygen acceptance among caregivers of sick children in Lagos and Jigawa states, which are two contrasting settings in Nigeria. METHODS: Between April 2022 and January 2023, we conducted an exploratory qualitative study using reflexive thematic analysis, involving semistructured interviews with caregivers (Jigawa=18 and Lagos=7), HCPs (Jigawa=7 and Lagos=6) and community group discussions (Jigawa=4 and Lagos=5). We used an inductive-deductive approach to identify codes and themes through an iterative process using the theoretical framework of acceptability and the normalisation process theory as the analytic lens. RESULTS: Medical oxygen prescription was associated with tension, characterised by fear of death, hopelessness about a child's survival and financial distress. These were driven by community narratives around oxygen, past negative experiences and contextual differences between both settings. Caregiver acceptance of medical oxygen was a sense-making process from apprehension and scepticism about their child's survival chances to positioning prescribed oxygen as an 'appropriate' or 'needed' intervention. Achieving this transition occurred through various means, such as trust in HCPs, a perceived sense of urgency for care, previous positive experience of oxygen use and a symbolic perception of oxygen as a technology. Misconceptions and pervasive negative narratives were acknowledged in Jigawa, while in Lagos, the cost was a major reason for oxygen refusal. CONCLUSION: Non-acceptance of medical oxygen treatment for sick children is modifiable in the Nigerian context, with the root causes of refusal being contextually specific. Therefore, a one-size-fits-all policy is unlikely to work. Financial constraints and community attitudes should be addressed in addition to improving client-provider interactions.

Hypoxaemia and risk of death among children: rethinking oxygen saturation, risk-stratification, and the role of pulse oximetry in primary care.

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO2] 90-93%) and severe hypoxaemia (ie, SpO2 <90%). We suggest that moderate hypoxaemia in the primary care setting should prompt careful clinical re-assessment, consideration of referral, and close follow-up. We provide practical guidance to better support front-line health-care workers to use pulse oximetry, including rethinking traditional binary SpO2 thresholds and promoting a more nuanced approach to identification and emergency treatment of the severely ill child.

Effect of a participatory whole-systems approach on mortality in children younger than 5 years in Jigawa state, Nigeria (INSPIRING trial): a community-based, parallel-arm, pragmatic, cluster randomised controlled trial and concurrent mixed-methods process evaluation.

BACKGROUND: In 2019, Nigeria reported the highest mortality rate in children younger than 5 years globally. We aimed to assess a whole-systems approach to improving child mortality in northern Nigeria. METHODS: We conducted a community-based, parallel-arm, pragmatic, cluster randomised controlled trial in Kiyawa local government area, Jigawa state, Nigeria, and a concurrent mixed-methods process evaluation using ethnography and quantitative implementation monitoring. Trial clusters were population catchment areas of 32 government primary health-care facilities. Compounds were randomly sampled, proportional to cluster size, and all women aged 16-49 years and children younger than 5 years who were permanent residents were eligible for inclusion and recruited as the evaluation population. Children younger than 7 days were recruited but excluded from analysis. Evaluation clusters were allocated to intervention or control via simple randomisation with a 1:1 ratio. Cluster names were written on paper, folded, and placed in a container by community representatives. Different community representatives took out names one by one, with the first half assigned to receive the intervention. The intervention consisted of three components: participatory learning and action (PLA) groups for men and women (including compound heads [ie, the member of the compound that residents deemed most senior]), partnership defined quality scorecard (PDQS), and health-care worker capacity building; it was delivered from March 1, 2021, to Dec 31, 2022. We could not mask participants, field staff, or intervention-delivery staff to cluster allocation but baseline, endline, and follow-up data excluded information on cluster allocation. PLA groups involved separate groups of up to 25 men or women from all villages in the intervention clusters. The primary outcome was all-cause mortality in children aged 7 days to 59 months between Oct 1, 2021, and Sept 20, 2022, referred to as the evaluation period. The trial was prospectively registered (ISRCTN 39213655) and the protocol has been published. FINDINGS: We recruited 3800 compounds at baseline, with 12 893 children contributing to analysis of the primary outcome (7316 [56·8%] of 12 893 in the intervention group and 5577 [43·3%] in the control group). 6617 (51·3%) of 12 893 children were male, 6275 (48·7%) were female, and one (<0·1%) child had missing sex data. Sampled compounds randomly came from 388 (91·3%) of 425 villages in the 32 clusters. We conducted verbal autopsies for 1182 deaths, of which 369 (31·2%) were children aged 7 days to 59 months during the evaluation period. Of these 369, 91 (24·7%) were classified as pneumonia deaths. Children contributed a median 361 days (IQR 236-365) to the analysis, with 369 (2·9%) of 12 893 children censored on their date of death, 1545 (12·0%) on their 5th birthday, and 3392 (26·3%) on the date of the most recent follow-up in which their residence or survival status was known. We found no significant decrease in all-cause mortality (hazard ratio 0·95, 95% CI 0·68-1·33; p=0·79) or suspected pneumonia mortality (0·79, 0·43-1·46; p=0·46) in the intervention group. The process evaluation showed low coverage and issues in reach of the intervention, but qualitative data highlighted mechanisms for positive effects on health and relationships. INTERPRETATION: Our intervention did not affect mortality. However, due to the high child mortality in this region, further efforts should be made to adapt our participatory whole-systems approach to use communities of action within compounds. FUNDING: GSK and Save the Children UK. TRANSLATION: For the Hausa translation of the abstract see Supplementary Materials section.

What are the risk factors for death among children with pneumonia in low- and middle-income countries? A systematic review.

Background: Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an individual and population level. This review aimed to identify the most important risk factors for mortality among children aged under ten years with pneumonia. Methods: We systematically searched MEDLINE, EMBASE, and PubMed for observational and interventional studies reporting risk factors for mortality in children (aged two months to nine years) in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, assessed risk of bias using the EPHPP framework, and extracted data on demographic, clinical, and laboratory risk factors for death. We synthesized data descriptively and using Forest plots and did not attempt meta-analysis due to the heterogeneity in study design, definitions, and populations. Findings: We included 143 studies in this review. Hypoxaemia (low blood oxygen level), decreased conscious state, severe acute malnutrition, and the presence of an underlying chronic condition were the risk factors most strongly and consistently associated with increased mortality in children with pneumonia. Additional important clinical factors that were associated with mortality in the majority of studies included particular clinical signs (cyanosis, pallor, tachypnoea, chest indrawing, convulsions, diarrhoea), chronic comorbidities (anaemia, HIV infection, congenital heart disease, heart failure), as well as other non-severe forms of malnutrition. Important demographic factors associated with mortality in the majority of studies included age <12 months and inadequate immunisation. Important laboratory and investigation findings associated with mortality in the majority of studies included: confirmed Pneumocystis jirovecii pneumonia (PJP), consolidation on chest x-ray, pleural effusion on chest x-ray, and leukopenia. Several other demographic, clinical and laboratory findings were associated with mortality less consistently or in a small numbers of studies. Conclusions: Risk assessment for children with pneumonia should include routine evaluation for hypoxaemia (pulse oximetry), decreased conscious state (e.g. AVPU), malnutrition (severe, moderate, and stunting), and the presence of an underlying chronic condition as these are strongly and consistently associated with increased mortality. Other potentially useful risk factors include the presence of pallor or anaemia, chest indrawing, young age (<12 months), inadequate immunisation, and leukopenia.

Whose knowledge counts? Involving communities in intervention and trial design using community conversations.

BACKGROUND: Current debates in Global Health call for expanding methodologies to allow typically silenced voices to contribute to processes of knowledge production and intervention design. Within trial research, this has typically involved small-scale qualitative work, with limited opportunities for citizens to contribute to the structure and nature of the trial. This paper reports on efforts to move past typical formative trial work, through adaptation of community conversations (CCs) methodology, an action-oriented approach that engages large numbers of community members in dialogue. We applied the CC method to explore community perspectives about pneumonia and managing the health of children under-5 in Northern Nigeria to inform our pragmatic cluster randomised controlled trial evaluating a complex intervention to reduce under-5 mortality in Nigeria. METHODS: We conducted 12 rounds of community conversations with a total of 320 participants, in six administrative wards in Kiyawa Local Government Area, Jigawa state, our intervention site. Participants were male and female caregivers of children under five. Conversations were structured around participatory learning and action activities, using drawings and discussion to reduce barriers to entry. During activities participants were placed in subgroups: younger women (18-30 years of age), older women (31-49 years) and men (18 years above). Discussions were conducted over three 2-h sessions, facilitated by community researchers. Following an initial analysis to extract priority issues and perspectives on intervention structure, smaller focus group discussions were completed with participants in five new sites to ensure all 11 administrative wards in our study site contributed to the design. RESULTS: We identified enabling and limiting factors which could shape the future trial implementation, including complex power relationships within households and wider communities shaping women's health decision-making, and the gendered use of space. We also noted the positive engagement of participants during the CC process, with many participants valuing the opportunity to express themselves in ways they have not been able to in the past. CONCLUSIONS: CCs provide a structured approach to deep meaningful engagement of everyday citizens in intervention and trial designs, but require appropriate resources, and commitment to qualitative research in trials. TRIAL REGISTRATION: ISRCTN39213655. Registered on 11 December 2019.

Pneumonia knowledge and care seeking behavior for children under-five years in Jigawa, Northwest Nigeria: a cross-sectional study.

Background: Between 2013 and 2022, Nigeria did not meet globally defined targets for pneumonia control, despite some scale-up of vaccinations, oxygen and antibiotics. A deliberate focus on community-based programs is needed to improve coverage of protective, preventive and treatment interventions. We therefore aimed to describe caregiver knowledge and care seeking behaviour for childhood pneumonia, in a high child mortality setting in Nigeria, to inform the development of effective community-based interventions for pneumonia control. Methods: We conducted a cross-sectional household survey in Kiyawa Local Government Area, Jigawa State, Nigeria between December 2019 and March 2020. We asked caregivers about their knowledge of pneumonia symptoms, prevention, risks, and treatment. A score of 1 was assigned for each correct response. We showed them videos of pneumonia specific symptoms and asked (1) if their child had any respiratory symptoms in the 2-weeks prior; (2) their subsequent care-seeking behaviour. Multivariate regressions explored socio-demographic and clinical factors associated with care seeking. Results: We surveyed 1,661 eligible women, with 2,828 children under-five. Only 4.9% of women could name both cough and difficulty/fast breathing as pneumonia symptoms, and the composite knowledge scores for pneumonia prevention, risks and treatment were low. Overall, 19.0% (536/2828) of children had a report of pneumonia specific symptoms in the prior two-weeks, and of these 32.3% (176/536) were taken for care. The odds of care seeking was higher among children: with fever (AOR:2:45 [95% CI: 1.38-4.34]); from wealthiest homes (AOR: 2:13 [95% CI: 1.03-4.38]) and whose mother first married at 20-26 years compared to 15-19 years (AOR: 5.15 [95% CI: 1.38-19.26]). Notably, the caregiver's knowledge of pneumonia was not associated with care seeking. Conclusion: While some socio-demographic factors were associated with care seeking for children with symptoms of Acute Respiratory Infection (ARI), caregiver's knowledge of the disease was not. Therefore, when designing public health interventions to address child mortality, information-giving alone is likely to be insufficient.

Continuous Positive Airway Pressure (CPAP) for severe pneumonia in low- and middle-income countries: A systematic review of contextual factors.

Background: Continuous positive airway pressure (CPAP) may have a role in reducing the high mortality in children less than 5 years with World Health Organization (WHO) severe pneumonia. More evidence is needed to understand important contextual factors that impact on implementation, effectiveness, and safety in low resource settings. Methods: We conducted a systematic review of Medline, Embase and Pubmed (January 2000 to August 2020) with terms of "pneumonia", "CPAP" and "child". We included studies that provided original clinical or non-clinical data on the use of CPAP in children (28 days-4 years) with pneumonia in low- or middle-income countries. We used standardised tools to assess study quality, and grade levels of evidence for clinical conclusions. Results are presented as a narrative synthesis describing context, intervention, and population alongside outcome data. Results: Of 902 identified unique references, 23 articles met inclusion criteria, including 6 randomised controlled trials, one cluster cross over trial, 12 observational studies, 3 case reports and 1 cost-effectiveness analysis. There was significant heterogeneity in patient population, with wide range in mortality among participants in different studies (0%-55%). Reporting of contextual factors, including staffing, costs, and details of supportive care was patchy and non-standardised. Current evidence suggests that CPAP has a role in the management of infants with bronchiolitis and as escalation therapy for children with pneumonia failing standard-flow oxygen therapy. However, CPAP must be implemented with appropriate staffing (including doctor oversight), intensive monitoring and supportive care, and technician and infrastructure capacity. We provide practical guidance and recommendations based on available evidence and published expert opinion, for the adoption of CPAP into routine care in low resource settings and for reporting of future CPAP studies. Conclusions: CPAP is a safe intervention in settings that can provide intensive monitoring and supportive care, and the strongest evidence for a benefit of CPAP is in infants (aged less than 1 year) with bronchiolitis. The available published evidence and clinical experience can be used to help facilities assess appropriateness of implementing CPAP, guide health workers in refining selection of patients most likely to benefit from it, and provide a framework for components of safe and effective CPAP therapy. Protocol registration: PROSPERO registration: CRD42020210597.

Can child pneumonia in low-resource settings be treated without antibiotics? A systematic review & meta-analysis.

Background: WHO guidelines recommend the use of antibiotics for all cases of pneumonia in children, despite the majority being caused by viruses. We performed a systematic review and meta-analysis to determine which children aged 2-59 months with WHO-defined fast breathing pneumonia, if any, can be safely treated without antibiotics. Methods: We systematically searched medical databases for articles published in the last 20 years. We included both observational and interventional studies that compared antibiotics to no antibiotics in children aged 2-59 months diagnosed with fast breathing pneumonia in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, and assessed for risk of bias using the Effective Public Health Practice Project (EPHPP) framework. Overall, we included 13 studies in this review. We performed a meta-analysis of four included studies comparing amoxicillin to placebo. Results: Most children with fast breathing pneumonia will have a good outcome, regardless of whether or not they are treated with antibiotics. Meta-analysis of four RCTs comparing amoxicillin to placebo for children with pneumonia showed higher risk of treatment failure in the placebo group (odds ratio OR 1.40, 95% confidence interval CI = 1.00-1.96). We did not identify any child pneumonia subgroups in whom antibiotics can be safely omitted. Limited data suggest that infants with clinically-diagnosed bronchiolitis are a particular low-mortality group who may be safely treated without antibiotics in some contexts. Conclusions: Children with WHO-defined fast breathing pneumonia in LMICs should continue to be treated with antibiotics. Future studies should seek to identify which children stand to benefit most from antibiotic therapy, and identify those in whom antibiotics may not be required, and in which circumstances.

Childhood pneumonia in humanitarian emergencies in low- and middle-income countries: A systematic scoping review.

Background: Humanitarian emergencies increase many risk factors for pneumonia, including disruption to food, water and sanitation, and basic health services. This review describes pneumonia morbidity and mortality among children and adolescents affected by humanitarian emergencies. Methods: We searched MEDLINE, EMBASE, and PubMed databases for publications reporting pneumonia morbidity or mortality among children aged 1 month to 17 years in humanitarian emergencies (eg, natural disaster, armed conflict, displacement) in low- and middle-income countries (LMICs). Results: We included 22 papers published between January 2000 and July 2021 from 33 countries, involving refugee/displaced persons camps (n = 5), other conflict settings (n = 14), and natural disaster (n = 3). Population pneumonia incidence was high for children under 5 years of age (73 to 146 episodes per 100 patient-years); 6%-29% met World Health Organization (WHO) criteria for severe pneumonia requiring admission. Pneumonia accounted for 13%-34% of child and adolescent presentations to camp health facilities, 7%-48% of presentations and admissions to health facilities in other conflict settings, and 12%-22% of admissions to hospitals following natural disasters. Pneumonia related deaths accounted for 7%-30% of child and adolescent deaths in hospital, though case-fatality rates varied greatly (0.5%-17.2%). The risk for pneumonia was greater for children who are: recently displaced, living in crowded settings (particularly large camps), with deficient water and sanitation facilities, and those who are malnourished. Conclusion: Pneumonia is a leading cause of morbidity and mortality in children and adolescents affected by humanitarian emergencies. Future research should address population-based pneumonia burden, particularly for older children and adolescents, and describe contextual factors to allow for more meaningful interpretation and guide interventions.

Management of tuberculosis infection in Victorian children: A retrospective clinical audit of factors affecting treatment completion.

BACKGROUND: Tuberculosis preventive treatment (TPT) is strongly recommended for children following infection with Mycobacterium tuberculosis because of their high risk of progression to active tuberculosis, including severe disseminated disease. We describe the implementation of TPT for children and adolescents with evidence of tuberculosis infection (TBI) at Victoria's largest children's hospital and examine factors affecting treatment completion. METHODS: We conducted a retrospective clinical audit of all children and adolescents aged <18 years diagnosed with latent TBI at the Royal Children's Hospital, Melbourne, between 2010 and 2016 inclusive. The primary outcome was treatment completion, defined as completing TPT to within one month of a target duration for the specified regimen (for instance, at least five months of a six-month isoniazid course), confirmed by the treating clinician. Factors associated with treatment adherence were evaluated by univariate and multivariate analysis. RESULTS: Of 402 participants with TBI, 296 (74%) met the criteria for treatment "complete". The most common TPT regimen was six months of daily isoniazid (377, 94%). On multivariate logistic regression analysis, treatment completion was more likely among children and adolescents who had refugee health screening performed (OR 2.31, 95%CI 1.34-4.00) or who were also treated for other medical conditions (OR 1.67 95%CI 1.0-2.85), and less likely among those who experienced side-effects (OR 0.32, 95%CI 0.11-0.94). However, TPT was generally well tolerated with side-effects reported in 15 participants (3.7%). CONCLUSION: Identification of factors associated with TPT completion and deficiencies in the existing care pathway have informed service provision changes to further improve outcomes for Victorian children and adolescents with TBI.

Cost-effectiveness and sustainability of improved hospital oxygen systems in Nigeria.

INTRODUCTION: Improving hospital oxygen systems can improve quality of care and reduce mortality for children, but we lack data on cost-effectiveness or sustainability. This study evaluated medium-term sustainability and cost-effectiveness of the Nigeria Oxygen Implementation programme. METHODS: Prospective follow-up of a stepped-wedge trial involving 12 secondary-level hospitals. Cross-sectional facility assessment, clinical audit (January-March 2021), summary admission data (January 2018-December 2020), programme cost data. INTERVENTION: pulse oximetry introduction followed by solar-powered oxygen system installation with clinical and technical training and support. PRIMARY OUTCOMES: (i) proportion of children screened with pulse oximetry; (ii) proportion of hypoxaemic (SpO2 <90%) children who received oxygen. Comparison across three time periods: preintervention (2014-2015), intervention (2016-2017) and follow-up (2018-2020) using mixed-effects logistic regression. Calculated cost-effectiveness of the intervention on child pneumonia mortality using programme costs, recorded deaths and estimated counterfactual deaths using effectiveness estimates from our effectiveness study. Reported cost-effectiveness over the original 2-year intervention period (2016-2017) and extrapolated over 5 years (2016-2020). RESULTS: Pulse oximetry coverage for neonates and children remained high during follow-up (83% and 81%) compared with full oxygen system period (94% and 92%) and preintervention (3.9% and 2.9%). Oxygen coverage for hypoxaemic neonates/children was similarly high (94%/88%) compared with full oxygen system period (90%/82%). Functional oxygen sources were present in 11/12 (92%) paediatric areas and all (8/8) neonatal areas; three-quarters (15/20) of wards had a functional oximeter. Of 32 concentrators deployed, 23/32 (72%) passed technical testing and usage was high (median 10 797 hours). Estimated 5-year cost-effectiveness US$86 per patient treated, $2694-4382 per life saved and $82-125 per disability-adjusted life year-averted. We identified practical issues for hospitals and Ministries of Health wishing to adapt and scale up pulse oximetry and oxygen. CONCLUSION: Hospital-level improvements to oxygen and pulse oximetry systems in Nigerian hospitals have been sustained over the medium-term and are a highly cost-effective child pneumonia intervention.

Hypoxaemia prevalence and management among children and adults presenting to primary care facilities in Uganda: A prospective cohort study.

Hypoxaemia (low blood oxygen) is common among hospitalised patients, increasing the odds of death five-fold and requiring prompt detection and treatment. However, we know little about hypoxaemia prevalence in primary care and the role for pulse oximetry and oxygen therapy. This study assessed the prevalence and management of hypoxaemia at primary care facilities in Uganda. We conducted a cross sectional prevalence study and prospective cohort study of children with hypoxaemia in 30 primary care facilities in Uganda, Feb-Apr 2021. Clinical data collectors used handheld pulse oximeters to measure blood oxygen level (SpO2) of all acutely unwell children, adolescents, and adults. We followed up a cohort of children aged under 15 years with SpO2<93% by phone after 7 days to determine if the patient had attended another health facility, been admitted, or recovered. Primary outcome: proportion of children under 5 years of age with severe hypoxaemia (SpO2<90%). Secondary outcomes: severe (SpO2<90%) and moderate hypoxaemia (SpO2 90-93%) prevalence by age/sex/complaint; number of children with hypoxaemia referred, admitted and recovered. We included 1561 children U5, 935 children 5-14 years, and 3284 adolescents/adults 15+ years. Among children U5, the prevalence of severe hypoxaemia was 1.3% (95% CI 0.9 to 2.1); an additional 4.9% (3.9 to 6.1) had moderate hypoxaemia. Performing pulse oximetry according to World Health Organization guidelines exclusively on children with respiratory complaints would have missed 14% (3/21) of severe hypoxaemia and 11% (6/55) of moderate hypoxaemia. Hypoxaemia prevalence was low among children 5-14 years (0.3% severe, 1.1% moderate) and adolescents/adults 15+ years (0.1% severe, 0.5% moderate). A minority (12/27, 44%) of severely hypoxaemic patients were referred; 3 (12%) received oxygen. We followed 87 children aged under 15 years with SpO2<93%, with complete data for 61 (70%), finding low rates of referral (6/61, 10%), hospital attendance (10/61, 16%), and admission (6/61, 10%) with most (44/61, 72%) fully recovered at day 7. Barriers to referral included caregiver belief it was unnecessary (42/51, 82%), cost (8/51, 16%), and distance or lack of transport (3/51, 6%). Hypoxaemia is common among acutely unwell children under five years of age presenting to Ugandan primary care facilities. Routine pulse oximetry has potential to improve referral, management and clinical outcomes. Effectiveness, acceptability, and feasibility of pulse oximetry and oxygen therapy for primary care should be investigated in implementation trials, including economic analysis from health system and societal perspectives.

Prevalence of pneumonia and malnutrition among children in Jigawa state, Nigeria: a community-based clinical screening study.

OBJECTIVE: To estimate the point prevalence of pneumonia and malnutrition and explore associations with household socioeconomic factors. DESIGN: Community-based cross-sectional study conducted in January-June 2021 among a random sample of households across all villages in the study area. SETTING: Kiyawa Local Government Area, Jigawa state, Nigeria. PARTICIPANTS: Children aged 0-59 months who were permanent residents in Kiyawa and present at home at the time of the survey. MAIN OUTCOME MEASURES: Pneumonia (non-severe and severe) defined using WHO criteria (2014 revision) in children aged 0-59 months. Malnutrition (moderate and severe) defined using mid-upper arm circumference in children aged 6-59 months. RESULTS: 9171 children were assessed, with a mean age of 24.8 months (SD=15.8); 48.7% were girls. Overall pneumonia (severe or non-severe) point prevalence was 1.3% (n=121/9171); 0.6% (n=55/9171) had severe pneumonia. Using an alternate definition that did not rely on caregiver-reported cough/difficult breathing revealed higher pneumonia prevalence (n=258, 2.8%, 0.6% severe, 2.2% non-severe). Access to any toilet facility was associated with lower odds of pneumonia (aOR: 0.56; 95% CI: 0.31 to 1.01). The prevalence of malnutrition (moderate or severe) was 15.6% (n=1239/7954) with 4.1% (n=329/7954) were severely malnourished. Being older (aOR: 0.22; 95% CI: 0.17 to 0.27), male (aOR: 0.77; 95% CI: 0.66 to 0.91) and having head of compound a business owner or professional (vs subsistence farmer, aOR 0.71; 95% CI: 0.56 to 0.90) were associated with lower odds of malnutrition. CONCLUSIONS: In this large, representative community-based survey, there was a considerable pneumonia and malnutrition morbidity burden. We noted challenges in the diagnosis of Integrated Management of Childhood Illness-defined pneumonia in this context.

Pulse oximetry and oxygen services for the care of children with pneumonia attending frontline health facilities in Lagos, Nigeria (INSPIRING-Lagos): study protocol for a mixed-methods evaluation.

INTRODUCTION: The aim of this evaluation is to understand whether introducing stabilisation rooms equipped with pulse oximetry and oxygen systems to frontline health facilities in Ikorodu, Lagos State, alongside healthcare worker (HCW) training improves the quality of care for children with pneumonia aged 0-59 months. We will explore to what extent, how, for whom and in what contexts the intervention works. METHODS AND ANALYSIS: Quasi-experimental time-series impact evaluation with embedded mixed-methods process and economic evaluation. SETTING: seven government primary care facilities, seven private health facilities, two government secondary care facilities. TARGET POPULATION: children aged 0-59 months with clinically diagnosed pneumonia and/or suspected or confirmed COVID-19. INTERVENTION: 'stabilisation rooms' within participating primary care facilities in Ikorodu local government area, designed to allow for short-term oxygen delivery for children with hypoxaemia prior to transfer to hospital, alongside HCW training on integrated management of childhood illness, pulse oximetry and oxygen therapy, immunisation and nutrition. Secondary facilities will also receive training and equipment for oxygen and pulse oximetry to ensure minimum standard of care is available for referred children. PRIMARY OUTCOME: correct management of hypoxaemic pneumonia including administration of oxygen therapy, referral and presentation to hospital. SECONDARY OUTCOME: 14-day pneumonia case fatality rate. Evaluation period: August 2020 to September 2022. ETHICS AND DISSEMINATION: Ethical approval from University of Ibadan, Lagos State and University College London. Ongoing engagement with government and other key stakeholders during the project. Local dissemination events will be held with the State Ministry of Health at the end of the project (December 2022). We will publish the main impact results, process evaluation and economic evaluation results as open-access academic publications in international journals. TRIAL REGISTRATION NUMBER: ACTRN12621001071819; Registered on the Australian and New Zealand Clinical Trials Registry.

Integrated Sustainable childhood Pneumonia and Infectious disease Reduction in Nigeria (INSPIRING) through whole system strengthening in Jigawa, Nigeria: study protocol for a cluster randomised controlled trial.

BACKGROUND: Child mortality remains unacceptably high, with Northern Nigeria reporting some of the highest rates globally (e.g. 192/1000 live births in Jigawa State). Coverage of key protect and prevent interventions, such as vaccination and clean cooking fuel use, is low. Additionally, knowledge, care-seeking and health system factors are poor. Therefore, a whole systems approach is needed for sustainable reductions in child mortality. METHODS: This is a cluster randomised controlled trial, with integrated process and economic evaluations, conducted from January 2021 to September 2022. The trial will be conducted in Kiyawa Local Government Area, Jigawa State, Nigeria, with an estimated population of 230,000. Clusters are defined as primary government health facility catchment areas (n = 33). The 33 clusters will be randomly allocated (1:1) in a public ceremony, and 32 clusters included in the impact evaluation. The trial will evaluate a locally adapted 'whole systems strengthening' package of three evidence-based methods: community men's and women's groups, Partnership Defined Quality Scorecard and healthcare worker training, mentorship and provision of basic essential equipment and commodities. The primary outcome is mortality of children aged 7 days to 59 months. Mortality will be recorded prospectively using a cohort design, and secondary outcomes measured through baseline and endline cross-sectional surveys. Assuming the following, we will have a minimum detectable effect size of 30%: (a) baseline mortality of 100 per 1000 livebirths, (b) 4480 compounds with 3 eligible children per compound, (c) 80% power, (d) 5% significance, (e) intra-cluster correlation of 0.007 and (f) coefficient of variance of cluster size of 0.74. Analysis will be by intention-to-treat, comparing intervention and control clusters, adjusting for compound and trial clustering. DISCUSSION: This study will provide robust evidence of the effectiveness and cost-effectiveness of community-based participatory learning and action, with integrated health system strengthening and accountability mechanisms, to reduce child mortality. The ethnographic process evaluation will allow for a rich understanding of how the intervention works in this context. However, we encountered a key challenge in calculating the sample size, given the lack of timely and reliable mortality data and the uncertain impacts of the COVID-19 pandemic. TRIAL REGISTRATION: ISRCTN 39213655 . Registered on 11 December 2019.

Oxygen systems strengthening as an intervention to prevent childhood deaths due to pneumonia in low-resource settings: systematic review, meta-analysis and cost-effectiveness.

OBJECTIVES: Increasing access to oxygen services may improve outcomes among children with pneumonia living in low-resource settings. We conducted a systematic review to estimate the impact and cost-effectiveness of strengthening oxygen services in low-income and middle-income countries with the objective of including oxygen as an intervention in the Lives Saved Tool. DESIGN: We searched EMBASE and PubMed on 31 March 2021 using keywords and MeSH terms related to 'oxygen', 'pneumonia' and 'child' without restrictions on language or date. The risk of bias was assessed for all included studies using the quality assessment tool for quantitative studies, and we assessed the overall certainty of the evidence using Grading of Recommendations, Assessment, Development and Evaluations. Meta-analysis methods using random effects with inverse-variance weights was used to calculate a pooled OR and 95% CIs. Programme cost data were extracted from full study reports and correspondence with study authors, and we estimated cost-effectiveness in US dollar per disability-adjusted life-year (DALY) averted. RESULTS: Our search identified 665 studies. Four studies were included in the review involving 75 hospitals and 34 485 study participants. We calculated a pooled OR of 0.52 (95% CI 0.39 to 0.70) in favour of oxygen systems reducing childhood pneumonia mortality. The median cost-effectiveness of oxygen systems strengthening was $US62 per DALY averted (range: US$44-US$225). We graded the risk of bias as moderate and the overall certainty of the evidence as low due to the non-randomised design of the studies. CONCLUSION: Our findings suggest that strengthening oxygen systems is likely to reduce hospital-based pneumonia mortality and may be cost-effective in low-resource settings. Additional implementation trials using more rigorous designs are needed to strengthen the certainty in the effect estimate.