Paediatrics (RCH) - Research Publications

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    Can child pneumonia in low-resource settings be treated without antibiotics? A systematic review & meta-analysis
    Walker, PJB ; Wilkes, C ; Duke, T ; Graham, HR (INT SOC GLOBAL HEALTH, 2022)
    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.
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    Continuous Positive Airway Pressure (CPAP) for severe pneumonia in low- and middle-income countries: A systematic review of contextual factors
    Wilkes, C ; Subhi, R ; Graham, HR ; Duke, T (INT SOC GLOBAL HEALTH, 2022)
    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.
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    Systematic review of the clinical outcomes of pneumonia with a penicillin-group resistant pneumococcus in respiratory and blood culture specimens in children in low- and middle-income countries
    Hume-Nixon, M ; Lim, R ; Russell, F ; Graham, H ; von Mollendorf, C ; Mulholland, K ; Gwee, A ; ARI, RG (INT SOC GLOBAL HEALTH, 2022)
    BACKGROUND: Streptococcus pneumoniae is one of the most common bacteria causing pneumonia and the World Health Organization (WHO) recommends first-line treatment of pneumonia with penicillins. Due to increases in the frequency of penicillin resistance, this systematic review aimed to determine the clinical outcomes of children with pneumonia in low- and middle-income countries (LMICs), with penicillin-group resistant pneumococci in respiratory and/or blood cultures specimens. METHODS: English-language articles from January 2000 to November 2020 were identified by searching four databases. Systematic reviews and epidemiological studies from LMICs that included children aged one month to 9 years and reported outcomes of pneumonia with a penicillin-resistant pneumococcus in respiratory and blood culture specimens with or without comparison groups were included. Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. A narrative synthesis of findings based on the results of included studies was performed. RESULTS: We included 7 articles involving 2864 children. One strong- and four medium-quality studies showed no difference in clinical outcomes (duration of symptoms, length of hospital stay and mortality) between those children with penicillin non-susceptible compared to susceptible pneumococci. Two weak quality studies suggested better outcomes in the penicillin-susceptible group. CONCLUSIONS: Current evidence suggests no difference in clinical outcomes of child pneumonia due to a penicillin-resistant S. pneumoniae and as such, there is no evidence to support a change in current WHO antibiotic guidelines.
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    Review of the role of additional treatments including oseltamivir, oral steroids, macrolides, and vitamin supplementation for children with severe pneumonia in low- and middle-income countries
    Hume-Nixon, M ; Graham, H ; Russell, F ; Mulholland, K ; Gwee, A ; Group, ARIR (INT SOC GLOBAL HEALTH, 2022)
    BACKGROUND: Pneumonia is a major cause of death in children aged under five years. As children with severe pneumonia have the highest risk of morbidity and mortality, previous studies have evaluated the additional benefit of adjunctive treatments such as oseltamivir, oral steroids, macrolides, and vitamin supplementation that can be added to standard antibiotic management to improve clinical outcomes. The study reviewed the evidence for the role of these additional treatments for children with severe pneumonia in low- and middle-income countries (LMICs). METHODS: Four electronic databases were searched for English-language articles between 2000 to 2020. Systematic reviews (SRs) with meta-analyses, comparative cohort studies, and randomised controlled trials (RCTs) from LMICs that reported clinical outcomes for children with severe pneumonia aged between one month to 9 years who received adjunct treatment in addition to standard care were included. Risk of bias of included SRs was assessed using AMSTAR 2, and of individual studies using the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies. RESULTS: Overall, the search identified 2147 articles, 32 of which were eligible, including 7 SRs and 25 RCTs. These studies evaluated zinc (4 SRs, 17 RCTs), Vitamin D (1 SR, 4 RCTs), Vitamin A (3 SRs, 1 RCT), Vitamin C (1 SR, 2 RCTs) and micronutrients (1 RCT). Most studies reported clinical outcomes of time to improvement, length of stay, and treatment failure (including mortality). No studies of oseltamivir, steroids, or macrolides fulfilling the inclusion criteria were identified. For zinc, pooled analyses from SRs showed no evidence of benefit. Similarly, a Cochrane review and one RCT found that Vitamin A did not improve clinical outcomes. For Vitamin D, an RCT evaluating a single high dose of 100 000 international units (IU) of vitamin D found a reduction in time to improvement, with 38%-40% documented vitamin D deficiency at baseline. However, two other studies of 1000 IU daily did not show any effect, but vitamin D status was not measured. For vitamin C, two studies found a reduction in time to symptom resolution in those with severe disease, with one reporting a shorter length of hospital stay. However, both studies were of weak quality. Most studies excluded malnourished children, and studies which included these children did not report specifically on the effect of micronutrients. CONCLUSIONS: This review found that adjunctive zinc and vitamin A, in addition to standard care, does not improve clinical outcomes in children with severe pneumonia in LMICs (strong evidence). However, a reduction in time to symptom resolution was reported with high dose vitamin D supplementation in children with documented vitamin D deficiency (strong evidence from one study) and vitamin C (weak evidence), although further research is needed, especially in underweight children.
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    Which children with chest-indrawing pneumonia can be safely treated at home, and under what conditions is it safe to do so? A systematic review of evidence from low- and middle-income countries
    Wilkes, C ; Graham, H ; Walker, P ; Duke, T (INT SOC GLOBAL HEALTH, 2022)
    BACKGROUND: WHO pneumonia guidelines recommend that children (aged 2-59 months) with chest indrawing pneumonia and without any "general danger sign" can be treated with oral amoxicillin without hospital admission. This recommendation was based on trial data from limited contexts whose generalisability is unclear. This review aimed to identify which children with chest-indrawing pneumonia in low- and middle-income countries can be safely treated at home, and under what conditions is it safe to do so. METHODS: We searched MEDLINE, EMBASE, and PubMed for observational and interventional studies of home-based management of children (aged 28 days to four years) with chest-indrawing pneumonia in low- or middle-income countries. RESULTS: We included 14 studies, including seven randomised trials, from a variety of urban and rural contexts in 11 countries. Two community-based and two hospital-based trials in Pakistan and India found that home treatment of chest-indrawing pneumonia was associated with similar or superior treatment outcomes to hospital admission. Evidence from trials (n = 3) and observational (n = 6) studies in these and other countries confirms the acceptability and feasibility of home management of chest-indrawing pneumonia in low-risk cases, so long as safeguards are in place. Risk assessment includes clinical danger signs, oxygen saturation, and the presence of comorbidities such as undernutrition, anaemia, or HIV. Pulse oximetry is a critical risk-assessment tool that is currently not widely available and can identify severely ill patients with hypoxaemia otherwise possibly missed by clinical assessment alone. Additional safeguards include caregiver understanding and ability to return for review. CONCLUSIONS: Home treatment of chest-indrawing pneumonia can be safe but should only be recommended for children confirmed to be low-risk and in contexts where appropriate care and safety measures are in place.
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    Childhood pneumonia in humanitarian emergencies in low- and middle-income countries: A systematic scoping review
    Chen, SJ ; Walker, PJB ; Mulholland, K ; Graham, HR (INT SOC GLOBAL HEALTH, 2022)
    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.
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    Quality of care for children with acute respiratory infections in health facilities: A comparative analysis of assessment tools
    Quach, A ; Tosif, S ; Graham, SM ; von Mollendorf, C ; Mulholland, K ; Graham, H ; Duke, T ; Russell, FM (INT SOC GLOBAL HEALTH, 2022)
    BACKGROUND: Severe childhood pneumonia requires treatment in hospital by trained health care workers. It is therefore important to determine if health facilities provide quality health services for children with acute respiratory infections (ARI), including pneumonia. Using established indicators from WHO to measure quality of care (QoC) as a reference standard, this review aims to evaluate how well existing tools assess QoC for children presenting to health facilities with ARI. METHODS: Existing assessment tools identified from a published systematic literature review that evaluated QoC assessment tools for children (<15 years) in health facilities for all health conditions were included in this ARI-specific review. 27 ARI-specific indicators or "quality measures" from the WHO "Standards for improving quality of care for children and young adolescents in health facilities" were selected for use as a reference standard to assess QoC for children presenting to health facilities with ARI symptoms. Each included assessment tool was evaluated independently by two paediatricians to determine how many of the WHO ARI quality measures were assessable by the tool. The assessment tools were then ranked in order of percentage of ARI quality measures assessable. RESULTS: Nine assessment tools that assessed QoC for children attending health facilities were included. Two hospital care tools developed by WHO had the most consistency with ARI-specific indicators, assessing 22/27 (81.5%) and 20/27 (74.1%) of the quality measures. The remaining tools were less consistent with the ARI-specific indicators, including between zero to 16 of the 27 quality measures. The most common indicators absent from the tools were assessment of appropriate use of pulse oximetry and administration of oxygen, how often oxygen supply was unavailable, and mortality rates. CONCLUSIONS: The existing WHO hospital-based QoC assessment tools are comprehensive but could be enhanced by improved data quality around oxygen availability and appropriate use of pulse oximetry and oxygen administration. Any tools, however, should be considered within broader assessments of QoC, rather than utilised in isolation. Further adaptation to local settings will improve feasibility and facilitate progress in the delivery of quality health care for children with ARI. REGISTRATION: The protocol of the original systematic review was registered in PROSPERO ID: CRD42020175652.
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    Global research priorities on COVID-19 for maternal, newborn, child and adolescent health
    Ahmed, ASMNU ; Maamri, A ; Falade, AG ; Ayede, AI ; Bhutta, A ; Gambhir, A ; Tagarro, A ; Abdelmegeid, A ; Ahmadi, AR ; Barros, AJD ; Mekasha, A ; Srinivasaiyer, AK ; Araujo da Silva, AR ; Schultz, A ; Fatima, B ; Dhar, B ; Magowan, B ; Wills, B ; Raynes-Greenow, C ; Homer, C ; Maclennan, C ; Ward, C ; Garcia, DM ; Ross, D ; Murdoch, D ; Wilson, DJ ; Adejuyigbe, E ; Stasii, E ; Scudder, E ; Sacks, E ; McCollum, ED ; Althabe, F ; Russell, F ; Kumar, GS ; Sommerfelt, H ; Graham, H ; Blencowe, H ; Tappis, H ; Saloojee, H ; Ben Masaud, HA ; Tiwary, H ; Asiodu, I ; Newton, JB ; Bourdaire, J ; Adze, JA ; Martines, J ; Lozano, JM ; Walson, J ; Rankin, J ; Allegaert, K ; Pelle, KG ; Edmond, K ; Rabiei, K ; Rasmussen, KM ; Yunis, K ; Ferguson, L ; Greenslade, L ; Kiapi, L ; Noguchi, L ; Bont, L ; Day, LT ; Mofenson, L ; Aboumayaleh, M ; Aquzouz, M ; Wahba, M ; Nagai, M ; Knight, M ; Melkumova, M ; Jenyfa, M ; Neuman, MI ; Meremikwu, M ; Kinney, M ; Gravett, M ; Hawkes, MT ; Pacque, M ; Walsh, M ; McGuire, MK ; AlShawafi, NA ; Khuri-Bulos, N ; Thacker, N ; Rollins, N ; Kissoon, N ; Starets, O ; Picone, O ; Oladapo, OT ; Erdeve, O ; Smith, PB ; Van de Perre, P ; Kumar, P ; Mangtani, P ; Abbas, Q ; Khatoon, R ; Bahl, R ; Lodha, R ; Grais, R ; Richards-Kortum, R ; Rasaily, R ; Aryeetey, R ; Pattinson, R ; Petrucci, R ; Rossi, R ; Pace, RM ; Yoshida, S ; Walani, SR ; Godakandage, SSP ; Bauler, S ; Comstock, SS ; Basu, S ; Kebede, S ; Saha, S ; Bhatnagar, S ; Lee, SK ; Gupta, S ; Antara, SN ; Downe, S ; Freedman, S ; Lye, SJ ; Miller, S ; Sulimani, S ; Ley, SH ; Mangal, TD ; Lavin, T ; Shi, T ; Florin, TA ; Sundekilde, UK ; Baltag, V ; Valdes, V ; Cherniak, W ; Bin Nisar, Y ; Shamszai, ZZ ; Navabi, ZS (INT SOC GLOBAL HEALTH, 2021)
    BACKGROUND: This research prioritization aimed to identify major research gaps in maternal, newborn, child and adolescent health (MNCAH) to help mitigate the direct and indirect effects of the COVID-19 pandemic. METHODS: We adapted the Child Health and Nutrition Research Initiative methodology. We defined scope, domains, themes and scoring criteria. We approached diverse global experts via email to submit their research ideas in MNCAH and MNCAH-related cross-cutting/health systems area. We curated the research ideas as research questions (RQs) and sent them to the consenting experts for scoring via the online link. For each RQ, the research priority score (RPS) was calculated as an average of individual criterion scores and ranked based on RPS in each area. RESULTS: We identified top-ranked 10 RQs in each maternal, newborn, and child and adolescent health and 5 in the cross-cutting/health systems area. In maternal health, indirect effects on care, measures to improve care, health risks and outcomes, and preventing and managing SARS-CoV-2 infection/COVID-19 disease were priority RQs. In newborn health, clinical characterization and managing SARS-CoV-2 infection/COVID-19 disease, mode of transmission and interventions to prevent transmission were the focus. For child and adolescent health, top-ranked RQs were indirect effects on care, clinical status and outcomes, interventions to protect against SARS-CoV-2 infection/COVID-19 disease, and educational institute-related RQs. The cross-cutting RQs were the effects of the pandemic on availability, access, care-seeking and utilization of MNCAH services and potential solutions. CONCLUSIONS: We call on partners, including governments, non-governmental organizations, research institutes, and donors, to address this urgent research agenda.