Paediatrics (RCH) - Research Publications
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ItemPrevalence and outcome of lymphopenia in the Paediatric Intensive Care Unit: A prospective observational study(WILEY, 2022-12)AIM: Leukopenia (lymphopenia or neutropenia) may be an important marker of altered immunity and risk in children with critical illness. We aimed to evaluate the prevalence, course, and outcome of leukopenia in children admitted to Paediatric Intensive Care Unit (PICU). METHODS: All consecutive children (n = 200) admitted to PICU for any reason except malignancy or pre-existing immune deficiency were enrolled during June-August 2018. RESULTS: Median (interquartile range) age was 2.2 (0.6-8.5) years. About 52% (n = 103) had undergone a surgical procedure; 34% (n = 68) being cardiac surgery. Among medical illnesses, respiratory disorders were the most common (n = 39, 20%). Laboratory confirmed infections were present in 63 (31.5%) children. Leukopenia was identified in 135 (67.5%) children in the first week; 117 (58.5%) had only lymphopenia, 16 (8%) had both lymphopenia and neutropenia, and 2 (1%) had only neutropenia. In 69 children who had follow-up blood counts, lymphopenia resolved in 33 (48%) within 48 h and in another 20 (29%) by 4 days, and in a further 10 (14%) by 7 days. Children with lymphopenia had higher frequency of cardiac surgery, longer cardiopulmonary bypass time, greater need for invasive ventilation and vasopressor/inotrope therapy, and a higher probability of organ failure on day 4 and longer hospital stay. CONCLUSION: In critically ill children, lymphopenia is very common, often transient, but may be associated with unfavourable outcomes. Further studies with follow-up of blood counts in a larger sample are required to determine the course and outcomes of lymphopenia.
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ItemThe impact of the introduction of ten- or thirteen-valent pneumococcal conjugate vaccines on antimicrobial-resistant pneumococcal disease and carriage: A systematic literature review(INT SOC GLOBAL HEALTH, 2023)BACKGROUND: A systematic review in 2019 found reductions in antimicrobial resistance (AMR) of pneumococcal vaccine serotypes following pneumococcal conjugate vaccine (PCV) introduction. However, few low- or middle-income countries were included as not many had introduced higher valent PCVs (PCV10 or PCV13). The aim of our review is to describe AMR rates in these samples following the introduction of PCV10 or PCV13. METHODS: We conducted a systematic literature review of published papers that compared AMR for invasive pneumococcal disease (IPD), otitis media (OM) and nasopharyngeal carriage (NPC) samples following introduction of PCV10 or PCV13 to the pre-PCV period. Included studies published from July 2017 to August 2020 had a post-licensure observational study design and reported on our defined outcomes: IPD, OM, NPC and other (sputum or mixed invasive and non-invasive pneumococcal) isolates from people of all ages. Rates of AMR in the pre- and post-period were extracted. RESULTS: Data were extracted from 31 studies. Among IPD isolates, penicillin AMR rates following PCV10 or PCV13 introduction declined in 32% (n = 9/29) of included studies, increased in 34% (n = 10/29) and showed no change in 34% (n = 10/29). Cephalosporins AMR declined in 32% (n = 6/19) of studies, increased in 21% (n = 4/19) and showed no change in 47% (n = 9/19). Macrolides AMR declined in 33% (n = 4/12) of studies, increased in 50% (n = 6/12), and showed no change in 17% (n = 2/12). AMR to other antibiotics (including multidrug resistance) declined in 23% (n = 9/39) of studies, increased in 41% (n = 16/39) and showed no change in AMR in 36% (n = 14/39). There were no obvious differences between AMR; in setting which used PCV10 vs PCV13, according to time since PCV introduction or by World Bank income status of the respective country. The only study including OM isolates found no change in penicillin resistance. There were few studies on AMR in NPC (four studies), OM (one study) or other isolates (five studies). The results followed similar patterns to IPD isolates. CONCLUSIONS: We observed considerable heterogeneity in the findings between and within studies, e.g. no evidence of reduction in amoxicillin AMR with an increase in macrolides AMR. Reasons for such diverse findings include the period covered by different studies and variation in other pressures towards AMR.
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ItemWhat are the risk factors for death among children with pneumonia in low- and middle-income countries? A systematic review(INT SOC GLOBAL HEALTH, 2023)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.
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ItemInfluenza vaccine administration in a paediatric intensive care unit(WILEY, 2022-10)AIM: We describe the clinical profile of children and outcomes of influenza immunisation for patients in a paediatric intensive care unit (PICU). METHODS: Over two influenza seasons: 19/04/2018 to 07/08/2018 and 02/05/2019 to 10/10/2019, an immunisation nurse and PICU nurse coordinator met weekly and identified patients to receive the influenza vaccine. An inpatient list of PICU patients was screened for eligible patients: greater than 6 months of age, did not have imminent procedures (e.g. surgery) or were not critically unwell, as determined by the treating team, to receive the influenza vaccine. Patients were excluded if they had undergone surgery in the previous 24 hours or were being treated palliatively. RESULTS: Sixty patients in PICU were identified, with 43% (26/60) receiving the vaccine while in PICU and 17% (10/60) once discharged from PICU to the general ward environment. The majority of patients immunised were in PICU due to cardiac surgery/cardiology or general medical conditions, such as cerebral palsy or RSV bronchiolitis. There were no reported adverse events following immunisation. CONCLUSIONS: We have demonstrated the suitability and acceptability of children in the PICU receiving the seasonal influenza vaccine and tailored interventions to follow-up once discharged from PICU to optimise protection.
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ItemCan child pneumonia in low-resource settings be treated without antibiotics? A systematic review & meta-analysis(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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ItemPerception and experience of clinicians and caregivers in treating childhood severe pneumonia and hypoxemia using bubble continuous positive airway pressure in Ethiopian tertiary and general hospitals.(Public Library of Science (PLoS), 2022)BACKGROUND: In low and middle-income countries (LMICs), severe pneumonia with hypoxemia is the leading cause of child deaths, even with the provision of WHO-recommended antibiotic therapy, oxygen therapy and other supportive care. Previous studies found positive outcomes from the use of bubble continuous positive airway pressure (bCPAP) for treating these children compared to the standard oxygen therapy. Due to lack of data on the perceptions and experiences of hospital health care workers and caregivers of children on the feasibility and acceptability of bCPAP in treating children with severe pneumonia and hypoxemia in real-life settings, we examined these issues in tertiary and general hospitals in Ethiopia. METHODS: As part of a three-stages clinical trial, this qualitative study was conducted in two tertiary (stage I) and two general (stage II) hospitals from September 2019 to July 2020. During stages I and II, we have consecutively enrolled children with severe pneumonia and hypoxemia and put them on bCPAP to examine its feasibility and acceptability by clinicians and parents. A total of 89 children were enrolled (49 from two tertiary and 40 from two general hospitals). Then qualitative data were collected through 75 repeated in-depth interviews by social-science experts with purposively selected 30 hospital health workers and 15 parents of 12 children who received bCPAP oxygen therapy in the hospitals. Interview data were supplemented by 6 observations in the hospitals. Data were analyzed using a thematic approach. RESULTS: Identified structural and functional challenges for the introduction of bCPAP in treating childhood severe pneumonia and hypoxemia in the study hospitals include: inadequate number of pulse oximeters; unavailability of nasal prongs with age-specific size; inadequate and non-functioning oxygen flow meters, concentrator, and cylinders; disruption in power-supply; and inadequate number of staff. The opportunities in introducing bCPAP oxygen therapy included the availability of a dedicated corner for the study patients situated in front of nurse's station, required medicines and satisfactory level of clinicians' knowledge and skills for treating severe pneumonia patients. Additionally, the identified operational challenges were occasional lack of bubbling in the water-filled plastic bottle, lack of stand for holding the water-filled plastic bottle, and delayed shifting of oxygen source from an oxygen concentrator to a cylinder, particularly during electricity disruption. Participants (clinicians and parents) expressed their satisfaction as bCPAP oxygen therapy was found to be simple to handle, children had ease of breathing and recovered fast without major ill effects. CONCLUSION: Our study identified some important structural, functional, and operational challenges that need to be addressed before implementation of bCPAP oxygen therapy especially in frontline general hospitals with limited resources. In spite of these observed challenges, the clinicians and caregivers were highly satisfied with the overall performance of bCPAP oxygen therapy.
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ItemContinuous Positive Airway Pressure (CPAP) for severe pneumonia in low- and middle-income countries: A systematic review of contextual factors(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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ItemEffectiveness of Bubble Continuous Positive Airway Pressure (BCPAP) for Treatment of Children Aged 1-59 Months with Severe Pneumonia and Hypoxemia in Ethiopia: A Pragmatic Cluster Randomized Controlled Clinical Trial.(MDPI AG, 2022-08-23)Despite the beneficial effect of bubble continuous positive airway pressure (BCPAP) oxygen therapy for children with severe pneumonia under the supervision of physicians that has been shown in different studies, effectiveness trials in developing country settings where low-flow oxygen therapy is the standard of care are still needed. Thus, the aim of this study is to assess the effectiveness of bubble CPAP oxygen therapy compared to the WHO standard low-flow oxygen therapy among children hospitalized with severe pneumonia and hypoxemia in Ethiopia. This is a cluster randomized controlled trial where six district hospitals are randomized to BCPAP and six to standard WHO low-flow oxygen therapy. The total sample size is 620 per arm. Currently, recruitment of the patients is still ongoing where the management and follow-up of the enrolled patients are performed by general physicians and nurses under the supervision of pediatricians. The primary outcome is treatment failure and main secondary outcome is death. We anticipate to complete enrollment by September 2022 and data analysis followed by manuscript writing by December 2022. Findings will also be disseminated in December 2022. Our study will provide data on the effectiveness of BCPAP in treating childhood severe pneumonia and hypoxemia in a real-world setting.
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ItemCost-effectiveness and sustainability of improved hospital oxygen systems in Nigeria(BMJ PUBLISHING GROUP, 2022-08)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.
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ItemCharacteristics, management and changing incidence of children with empyema in a paediatric intensive care unit(WILEY, 2022-06)AIM: Paediatric intensive care unit (PICU) admissions for empyema increased following the 13-valent pneumococcal conjugate vaccine (PCV13). We describe the clinical characteristics, management and outcomes for children with empyema and compare incidence before and after PCV13. METHODS: Retrospective study of patients <18 years admitted to The Royal Children's Hospital Melbourne PICU with empyema between January 2016 and July 2019. We investigated the incidence of empyema during two time periods: 2007-2010 (pre-PCV13) and 2016-2019 (post-PCV13). RESULTS: Seventy-one children (1.9% of all PICU admissions) were admitted to PICU with empyema between 2016 and 2019. Sixty-one (86%) had unilateral disease, 11 (16%) presented with shock and 44 (62%) were ventilated. Streptococcus pneumoniae and group A Streptococcus were the most commonly identified pathogens. Forty-five (63%) were managed with video-assisted thoracoscopic surgery (VATS). There was a 31% reduction in empyema hospitalisations as a proportion of all hospitalisations (IRR 0.69, 95% CI 0.59-0.8), but a 2.8-fold increase in empyema PICU admissions as a proportion of all PICU admissions (95% CI 2.2-3.5, P < 0.001). For the PICU cohort, this was accompanied by reduction in PIM2 probability of death (median 1% vs. 1.9%, P = 0.02) and duration of intubation (median 69 h vs. 126.5 h, P = 0.045). CONCLUSIONS: In children with empyema in PICU 62% required ventilation, 16% had features of shock and 63% received VATS. Empyema admissions, as a proportion of all PICU admissions, increased in the era post-PCV13 compared to pre-PCV13 despite no increase in illness severity at admission.