Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups. The group identified key challenges to paediatric critical care research, including lower patient numbers than for adult critical care, heterogeneity related to cognitive development, comorbidities and illness or injury, consent challenges, disproportionately little research funding for paediatric critical care, and poor infrastructure in resource-limited settings. A seven-point roadmap was proposed: (1) formation of an international paediatric critical care research network; (2) development of a web-based toolkit library to support paediatric critical care trials; (3) establishment of a global paediatric critical care trial repository, including systematic prioritisation of topics and populations for interventional trials; (4) development of a harmonised trial minimum set of trial data elements and data dictionary; (5) building of infrastructure and capability to support platform trials; (6) funder advocacy; and (7) development of a collaborative implementation programme. Implementation of this roadmap will contribute to the successful design and conduct of trials that match the needs of globally diverse paediatric populations.

Background Paediatric sepsis remains a significant contributor to morbidity and mortality, particularly in low- and middle-income countries (LMICs), where healthcare resources are often limited. Paediatric sepsis bundles, which include prompt administration of antibiotics, fluid resuscitation and continuous organ function monitoring, are crucial for improving outcomes, especially when initiated within the first ‘golden hour’ of sepsis recognition. These bundles, adapted from adult sepsis care protocols through the Surviving Sepsis Campaign, are increasingly emphasised in global sepsis management guidelines. However, the implementation of these protocols in LMICs is challenged by resource limitations and systemic barriers.Methods This situational analysis, conducted at two hospitals in Ghana—a tertiary facility and a district (secondary) facility—maps the availability of critical resources for paediatric sepsis care through a structured environmental scan using survey methodology. We assess staffing levels, access to medications, airway support and diagnostic capabilities. Methods were conceptualised through inner and outer settings of the Consolidated Framework for Implementation Research (CFIR) and reported through the Donabedian model for healthcare quality.Results This study compared paediatric care at a tertiary hospital (Komfo Anokye Teaching Hosptial (KATH)) and a district hospital (Presbyterian Hospital, Agogo (PreHA)) in Ghana, highlighting KATH’s emergency and intensive care unit (ICU) services, specialised staff and broader respiratory support. PreHA, although without a paediatric-specific ICU, leveraged research funding to enhance clinical care capacity. Both hospitals experienced regular power outages but had reliable generators, and while they offered basic medications and treatments, resource limitations, including out-of-pocket costs for families, impacted access to essential medications and laboratory tests.Conclusion Concerns around resource availability, compounded by structural determinants such as financial barriers and historical underfunding hypothesised to be rooted in colonialism, highlight the need for context-sensitive adaptations of paediatric sepsis bundles. Our findings underscore the importance of a participatory approach to guideline adaptation and resource distribution, incorporating local expertise and addressing structural inequities to improve paediatric sepsis outcomes in Ghana. Future qualitative research will explore pre- and peri-hospital barriers to care and inform more effective, contextually appropriate interventions.

Background Children in resource-constrained settings (RCS) have disproportionately high illness and mortality; however, the prevalence in RCS of paediatric acute critical illness (P-ACI; life-threatening conditions that require time-sensitive interventions) is unknown. Most P-ACI can be managed with basic critical care (stabilisation, fluid resuscitation, oxygen, and vital-organ support), but RCS hospitals often lack such essential services. This study estimated the prevalence and examined the aetiology of P-ACI among children at RCS hospitals to support critical care capacity building and inform resource allocation. Methods We conducted a hybrid prospective cohort and multinational point prevalence study of acutely ill or injured children aged 28 days to 14 years who presented to RCS hospitals on four designated days between July 20, 2021, and July 12, 2022. We measured the proportion of participants with P-ACI, applying the definition for acute paediatric critical illness (DEFCRIT) framework for research in resource-variable settings, and followed up admitted patients for hospital outcomes. In participants with P-ACI, we report diagnoses associated with critical illness. We used descriptive statistics to summarise site and cohort data by country sociodemographic category (Socio-demographic Index; SDI) and multivariable logistic regression to assess whether country sociodemographic category was independently associated with P-ACI. Findings The study included 46 sites, 19 countries, and 7538 children, among whom 2651 (352%) were admitted to hospital and 68 died (all-cause mortality 09% [95% CI 07-11]). 985 (131% [95% CI 123-139]) participants had P-ACI. Among all sociodemographic categories, P-ACI prevalence was highest (280% [260-301]; 512 of 1828 participants) in low-SDI countries (p<00001). Mortality among those with P-ACI was 63% (49-80; 62 deaths). The most common P-ACI diagnoses were pneumonia (152 [154%] of 985 participants), sepsis or septic shock (102 [104%]), and malaria (95 [96%]). In an adjusted model, country sociodemographic category was not significantly associated with P-ACI frequency. Among all 68 deaths in the study, 40 (59% [46-71]) occurred within 48 h of presentation. Interpretation P-ACI in RCS hospitals is common, associated with high mortality, disproportionately elevated in low- SDI countries, and associated with conditions that can be managed with basic critical care. This study underlines the need for investment in basic critical care services in RCS to address a major contributor to preventable mortality in hospitalised children.

Background Bubble continuous positive airway pressure (bCPAP) is a low-cost, non-invasive respiratory support therapy for children with respiratory distress, but its effectiveness is dependent on the context. We aimed to understand contextual factors influencing bCPAP implementation for children aged 1–59 months in low-income and middle-income countries (LMICs) and to develop a theory explaining how these factors influence implementation outcomes. Methods In this realist review, we generated an initial programme theory comprising candidate context–mechanism–outcome configurations (CMOCs) via review of key references and team discussion. On July 25, 2023, we conducted a search for peer-reviewed and grey literature, without date restrictions, describing bCPAP use for paediatric respiratory distress in LMICs. We included references describing related contexts, mechanisms, or outcomes. We coded statements from the literature supporting each CMOC, iteratively revising and adding CMOCs using inductive and deductive logic. We assembled an international, interdisciplinary panel of 22 bCPAP stakeholders to refine CMOCs using iterative surveys, focus groups, and interviews until we reached thematic saturation. This realist review is registered with PROSPERO (CRD42023403584). Findings Of 1640 peer-reviewed references and eight grey literature references retrieved, 38 peer-reviewed articles and two grey literature documents were deemed eligible for inclusion after removal of duplicates and screening. After four rounds of expert surveys and three focus groups, we identified 18 CMOCs. CMOCs were synthesised into a final programme theory operating at five levels to influence implementation feasibility, fidelity, and sustainability: (1) the bCPAP device, (2) local partnerships and infrastructure, (3) clinical and technical teams, (4) caregivers and the community, and (5) institutional practices. Interpretation Using realist methods with a diverse, international stakeholder panel, we generated a theory that could explain how bCPAP therapy works in different contexts. This theory could be leveraged to enhance the rigour of future bCPAP implementation trials. Funding Yale National Clinician Scholars Program, US National Center for Advancing Translational Science (TL1TR001864), and National Heart, Lung, and Blood Institute (T32HL155000).

Pneumonia is the leading cause of death in children, however, the microbial aetiology of pneumonia is not well elucidated in low- and middle-income countries. Our study was aimed at determining the microbial aetiologies of childhood pneumonia and associated risk factors in HIV and non-HIV infected children. We conducted a case-control study that enrolled children with pneumonia as cases and non-pneumonia as controls from July 2017 to May 2020. Induced sputum and blood samples were investigated for microbial organisms using standard microbiological techniques. DNA/RNA was extracted from sputum samples and tested for viral and bacterial agents. Four hundred and four (404) subjects consisting of 231 (57.2%) cases and 173 (42.8%) controls were enrolled. We identified a significant (p = 0.011) proportion of viruses in cases (125; 54.1%, 95%CI: 47.4-60.7) than controls (71; 33.6%, 95%CI: 33.6-48.8) and these were mostly contributed to by Respiratory Syncytial Virus. Staphylococcus aureus (16; 4.0%), Klebsiella spp. (15, 3.7%) and Streptococcus pneumoniae (8, 2.0%) were the main bacterial agents identified in sputum or induced sputum samples. HIV infected children with viral-bacterial co-detection were found to have very severe pneumonia compared to those with only viral or bacterial infection. Indoor cooking (OR = 2.36; 95%CI:1.41-3.96) was found to be associated with pneumonia risk in patients. This study demonstrates the importance of various microbial pathogens, particularly RSV, in contributing to pneumonia in HIV and non-HIV paediatric populations. There is a need to accelerate clinical trials of RSV vaccines in African populations to support improvement of patient care.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.

Background/purpose Sepsis is a leading cause of morbidity, mortality and healthcare utilisation for children worldwide, particularly in resource-limited regions. In Kumasi, Ghana, organ system failure and mortality in children who present to the emergency department (ED) with symptoms of sepsis are often due to late presentation and lack of recognition and implementation of time-critical evidence-based interventions. The purpose of this study was to assess the barriers and facilitators for families in seeking healthcare for their septic children; and to understand the barriers and facilitators for ED providers in Kumasi to recognise and implement sepsis bundle interventions.Design Single-centre qualitative interviews of 39 caregivers and 35 ED providers in a teaching hospital in Kumasi, Ghana.Results Thematic analysis of data from caregivers about barriers included: fear of hospital, finances, transportation, delay from referring hospital, cultural/spiritual differences, limited autonomy and concerns with privacy and confidentiality. Negative impacts on family life included financial strain and neglect of other children. ED providers reported barriers included: lack of training, poor work environment and accessibility of equipment. Facilitators from caregivers and providers included some support from the National Health Insurance. Caregivers reported having positive experiences with frontline clinicians, which encouraged them to return to seek health services.Implications Qualitative structured interviews identified facilitator and critical barrier themes about seeking healthcare, and sepsis identification/management in the paediatric population arriving for care in our centre in Kumasi, Ghana. This study highlights significant deficiencies in healthcare systems that make sepsis management challenging in these settings.

Background:Craniofacial Trauma and Anomalies affect a substantial proportion of the global society, especially those in the low-and middle-income countries (LMICs). The literature stresses the concept of a team approach for craniofacial surgery and the need for the interaction of many specialists to provide optimal care for the patient. Craniofacial surgery is practiced mainly in the advanced countries of Europe and America. This report describes the establishment of craniofacial care in an African country. It reports on 6-year early outcomes of craniofacial surgery in a low-resourced country, counting the successes, challenges, and prospects. Methods: The establishment of an international collaboration that facilitated the training in craniofacial surgery is described. A 6-year retrospective review of craniofacial surgery cases managed by the Multidisciplinary Cleft and Craniofacial team at the Komfo Anokye Teaching Hospital (KATH) was done from January 2016 to December 2022. Results: Two Ghanaian surgeons were trained in Alabama, USA (a maxillofacial surgeon and a neurosurgeon), then returned to Kumasi to begin a Craniofacial practice with the help of the craniofacial team in Children of Alabama Birmingham Al, USA. A total of 646 procedures were performed (616 cases of orofacial cleft, 20 cases of craniofacial anomalies, and 10 cases of craniofacial trauma involving the cranial vault or base of the skull). Ninety percent of the cases were cleft lip and palate, with the remainder being a mixture of isolated and syndromic craniosynostosis, craniofacial trauma, encephalocele, and craniofacial fibrous dysplasia. Conclusion: The Commonest craniofacial procedure performed was cleft lip and palate repair. Other surgeries were for the repair of velopharyngeal incompetence (VPI) and atypical facial clefts. Complex craniosynostosis and encephaloceles are also now being repaired at KATH. The foundation for a sub-regional center of excellence in cleft and craniofacial surgery is being laid in Ghana at KATH.

Introduction: Multicenter, multinational collaborative research has increased across differing resource capacities by country. Inconsistencies in ethical review processes is an under recognized resource limitation and in resource-limited settings across regions may lead to barriers to rapid deployment of important clinical studies. Methods: An ancillary prospective study of the global PARITY (pediatric acute critical illness study) point prevalence study of pediatric critical illness in resource-limited settings. We surveyed participating sites to explore ethical and board review processes. The aim of the study was to describe the time, costs, and barriers in obtaining institutional review board and ethics approval for a multinational, multicenter, non-interventional study in critically ill children involving low and middle-income countries. Results: Fifty-six centers completed the survey. Of those hospitals, 72% (n= 40) required a full board review of the global PARITY study prior to approval, and 17% (n=9) accepted an ethics approval from a separate institution. The frequency of institutional review board (irb) committee is variable between centers, 16% (n=9) weekly, 56% (n=31) meet every 1 – 2 month, 11% (n=6) every 3 – 6 month and in 16% (n=9) > six months. The IRB approval process took a median of 62 days (n=40; range 1-294 days). Sixteen centers (30%) reported costs associated with ethical review. The waived consent was approved by 71% (n=38) of the centers, and 23% (n=12) required a data sharing agreement. The protocol required translation to local language in 47% (n=26) centers, from which 25% (n=6) required a professional certificated translation. Of the centers surveyed, 32% (n=17) required a legal review of protocol or data sharing agreement. Conclusions: There is great variability in ethical review requirements and time of approval for a non-interventional multinational study of critically ill children in low and middle-income countries in both private and public hospitals. We show that this time resource must be considered when planning multinational studies. Enhancing the capacity for ethics and board review process across regions will allow for better matching of disease burden with clinical research and likely increase participation in this multicenter research.

Background: following the importation of the first Coronavirus disease 2019 (COVID-19) case into Africa on 14 February 2020 in Egypt, the World Health Organisation (WHO) regional office for Africa (AFRO) activated a three-level incident management support team (IMST), with technical pillars, to coordinate planning, implementing, supervision, and monitoring of the situation and progress of implementation as well as response to the pandemic in the region. At WHO AFRO, one of the pillars was the health operations and technical expertise (HOTE) pillar with five sub-pillars: case management, infection prevention and control, risk communication and community engagement, laboratory, and emergency medical team (EMT). This paper documents the learnings (both positive and negative for consideration of change) from the activities of the HOTE pillar and recommends future actions for improving its coordination for future emergencies, especially for multi-country outbreaks or pandemic emergency responses. Method: we conducted a document review of the HOTE pillar coordination meetings’ minutes, reports, policy and strategy documents of the activities, and outcomes and feedback on updates on the HOTE pillar given at regular intervals to the Regional IMST. In addition, key informant interviews were conducted with 14 members of the HOTE sub pillar. Key Learnings: the pandemic response revealed that shared decision making, collaborative coordination, and planning have been significant in the COVID-19 response in Africa. The HOTE pillar’s response structure contributed to attaining the IMST objectives in the African region and translated to timely support for the WHO AFRO and the member states. However, while the coordination mechanism appeared robust, some challenges included duplication of coordination efforts, communication, documentation, and information management. Recommendations: we recommend streamlining the flow of information to better understand the challenges that countries face. There is a need to define the role and responsibilities of sub-pillar team members and provide new team members with information briefs to guide them on where and how to access internal information and work under the pillar. A unified documentation system is important and could help to strengthen intra-pillar collaboration and communication. Various indicators should be developed to constantly monitor the HOTE team’s deliverables, performance and its members.

Arias, A. V.; Lintner Rivera, M.; Shafi, N. I.; Anwar, A.; Bhutta, A. T.; Bleakly Kortz, T.; Agulnik, A.; Abbas, O. (Qalab; Abdelhafeez, Hafeez; Ali, Muhammad; Ammar, Hala; Appiah, John; Attebery, Jonah; Villalobos, Willmer Diaz; Ferreira, Daiane; Dambrauskas, Sebastián González; Habib, Muhammad Irfan; Lee, Jan Hau; Kissoon, Niranjan; Tekleab, Atnafu Mekonnen; Molyneux, Elizabeth M.; Morrow, Brenda M.; Nadkarni, Vinay M.; Rivera, Jocelyn; Silvers, Rebecca; Steere, Mardi; Tatay), Daniel Author Information

CLINICAL QUESTION What is the role of drug interventions in the treatment and prevention of covid-19? RECOMMENDATIONS The first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines. HOW this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven byan urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems. THE EVIDENCE A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence). UNDERSTANDING THE RECOMMENDATIONS The panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health anda patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy. UPDATES This isa living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline. READERS NOTE This is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number. SUBMITTED August 28 ACCEPTED August 31 As of 1 September 2020, 25 327 098 people worldwide have been diagnosed with covid-19, according to the international World Health Organization (WHO) dashboard. 1 The pandemic has claimed 848 255 lives, and a resurgence in the number of new cases and continued growth is some countries has threatened high resource and low resource countries alike.

López Barón, E.; Holloway, A.; Agulnik, A.; Abbas, Q.; Appiah, J. A.; Attebery, J. E.; He, D.; Caporal, P.; Fink, E. L.; Hooli, S.; Kissoon, N.; Lee, J. H.; Miller, E.; Muttalib, F.; Nielsen, K.; Puerto Torres, M.; Remy, K. E.; Andre Von Arnim, A. V.; Sakaan, F. M.; Tabor, E. A.; Wiens, M. O.; Kortz, T. B.; Bhutta, A. T.; Murthy, S. Author Information

Sakaan, F. M.1; Agulnik, A.1; Puerto Torres, M.1; Holloway