Efficacy of oral corticosteroids for acute preschool wheeze: a systematic review and individual participant data meta-analysis of randomised clinical trials.

BACKGROUND: Oral corticosteroids are commonly used for acute preschool wheeze, although there is conflicting evidence of their benefit. We assessed the clinical efficacy of oral corticosteroids by means of a systematic review and individual participant data (IPD) meta-analysis. METHODS: In this systematic review with IPD meta-analysis, we systematically searched eight databases (PubMed, Ovid Embase, CINAHLplus, CENTRAL, ClinicalTrials.gov, EudraCT, EU Clinical Trials Register, WHO Clinical Trials Registry) for randomised clinical trials published from Jan 1, 1994, to June 30, 2020, comparing oral corticosteroids with placebo in children aged 12 to 71 months with acute preschool wheeze in any setting based on the Population, Intervention, Comparison, Outcomes framework. We contacted principal investigators of eligible studies to obtain deidentified individual patient data. The primary outcome was change in wheezing severity score (WSS). A key secondary outcome length of hospital stay. We also calculated a pooled estimate of six commonly reported adverse events in the follow-up period of IPD datasets. One-stage and two-stage meta-analyses employing a random-effects model were used. This study is registered with PROSPERO, CRD42020193958. FINDINGS: We identified 16 102 studies published between Jan 1, 1994, and June 30, 2020, from which there were 12 eligible trials after deduplication and screening. We obtained individual data from seven trials comprising 2172 children, with 1728 children in the eligible IPD age range; 853 (49·4%) received oral corticosteroids (544 [63·8%] male and 309 [36·2%] female) and 875 (50·6%) received placebo (583 [66·6%] male and 292 [33·4%] female). Compared with placebo, a greater change in WSS at 4 h was seen in the oral corticosteroids group (mean difference -0·31 [95% CI -0·38 to -0·24]; p=0·011) but not 12 h (-0·02 [-0·17 to 0·14]; p=0·68), with low heterogeneity between studies (I2=0%; τ2<0·001). Length of hospital stay was significantly reduced in the oral corticosteroids group (-3·18 h [-4·43 to -1·93]; p=0·0021; I2=0%; τ2<0·001). Subgroup analyses showed that this reduction was greatest in those with a history of wheezing or asthma (-4·54 h [-5·57 to -3·52]; pinteraction=0·0007). Adverse events were infrequently reported (four of seven datasets), but oral corticosteroids were associated with an increased risk of vomiting (odds ratio 2·27 [95% CI 0·87 to 5·88]; τ2<0·001). Most datasets (six of seven) had a low risk of bias. INTERPRETATION: Oral corticosteroids reduce WSS at 4 h and length of hospital stay in children with acute preschool wheeze. In those with a history of previous wheeze or asthma, oral corticosteroids provide a potentially clinically relevant effect on length of hospital stay. FUNDING: Asthma UK Centre for Applied Research.

Substantial Burden of Nonmedically Attended RSV Infection in Healthy-Term Infants: An International Prospective Birth Cohort Study.

BACKGROUND: During the first year of life, 1 in 4 infants develops a symptomatic respiratory syncytial virus (RSV) infection, yet only half seek medical attention. The current focus on medically attended RSV therefore underrepresents the true societal burden of RSV. We assessed the burden of nonmedically attended RSV infections and compared with medically attended RSV. METHODS: We performed active RSV surveillance until the age of 1 year in a cohort (n = 993) nested within the Respiratory Syncytial Virus Consortium in EUrope (RESCEU) prospective birth cohort study enrolling healthy term-born infants in 5 European countries. Symptoms, medication use, wheezing, and impact on family life were analyzed. RESULTS: For 97 of 120 (80.1%) nonmedically attended RSV episodes, sufficient data were available for analysis. In 50.5% (49/97), symptoms lasted ≥15 days. Parents reported impairment in usual daily activities in 59.8% (58/97) of episodes; worries, 75.3% (73/97); anxiety, 34.0% (33/97); and work absenteeism, 10.8% (10/93). Compared with medically attended RSV (n = 102, 9 hospital admissions), Respiratory Syncytial Virus NETwork (ReSViNET) severity scores were lower (3.5 vs 4.6, P < .001), whereas duration of respiratory symptoms and was comparable. CONCLUSIONS: Even when medical attendance is not required, RSV infection poses a substantial burden to infants, families, and society. These findings are important for policy makers when considering the implementation of RSV immunization. Clinical Trials Registration. ClinicalTrials.gov (NCT03627572).

Outdoor air pollution and near-fatal/fatal asthma attacks in children: A systematic review.

BACKGROUND: Globally, observational studies have demonstrated an association between high levels of air pollution and asthma attacks in children. It remains unclear whether and to what extent exposure may be associated with increased near-fatal/fatal attacks. OBJECTIVE: To systematically review the evidence for an association between ambient outdoor air pollution and fatal and/or near-fatal asthma (NFA). METHODS: Following Cochrane methodology, we searched MEDLINE, EMBASE, Web of Science, Scopus, and Open Grey electronic databases for studies reporting the association of fatal/NFA and air pollution (particulate matter [PM], sulfur dioxide, nitrogen dioxide, black carbon and ozone [O3 ]) in children. NFA was defined as requiring intensive care unit (ICU) management. RESULTS: Two reviewers independently screened 1358 papers. A total of 276 studies identified asthma attacks related to air pollution, 272 did not meet inclusion criteria after full-text review. Four observational studies described fatal/NFA, of which three addressed NFA. PM2.5 (per 12.5 µg/m3 increase) and O3 (per 22 ppb increase) were associated with NFA in one study (PM2.5, relative risk: 1.26, confidence interval [CI] [1.10-1.44]), O3  (1.19 [1.01-1.40]). PM10 was associated with ICU admission in the context of thunderstorm asthma. Elemental carbon was associated equally with NFA that did not require an ICU admission (p = 0.67). Studies of fatal asthma including children did not demarcate age within the analysis. CONCLUSIONS: Ozone and PM2.5 have been associated with NFA in children but synthesis is limited by the paucity of studies and methodological heterogeneity. Poor reporting of severities of asthma attacks hinders the assessment of whether outdoor air pollution is associated with an increased number of NFA/fatal attacks in children.

Lung clearance index (LCI2.5 ) changes after initiation of Elexacaftor/Tezacaftor/Ivacaftor in children with cystic fibrosis aged between 6 and 11 years: The "real-world" differs from trial data.

BACKGROUND: Elexacaftor in combination with Tezacaftor and Ivacaftor (ETI) became licensed in the United Kingdom in early 2022 for children aged 6-11 years with cystic fibrosis (CF) and an eligible mutation. Many in this age group have excellent prior lung health making quantitative measurement of benefit challenging. Clinical trials purport that lung clearance index (LCI2.5 ) measurement is most suitable for this purpose. OBJECTIVES: This study aimed to understand the clinical utility of LCI2.5 in detecting change after commencing ETI in the real world. PATIENT SELECTION/METHODS: Baseline anthropometric data were collected along with spirometry (forced expiratory volume in 1 s [FEV1 ], forced vital capacityFV and LCI2.5 measures in children aged 6-11 years with CF before starting ETI. Measures were repeated after a mean (range) of 8.2 (7-14) months of ETI treatment. The primary endpoint was a change in LCI2.5 , with secondary endpoints including change in FEV1 and change in body mass index (BMI) also reported. RESULTS: Twelve children were studied (seven male, mean age 9.5 years at baseline). Our study population had a mean (SD) LCI2.5 of 7.01 (1.14) and FEV1 of 96 (13) %predicted at baseline. Mean (95% confidence interval) changes in LCI2.5 [-0.7 (-1.4, 0), p = .06] and BMI [+0.7 (+0.1, +1.3), p = .03] were observed, along with changes in FEV1 of +3.1 (-1.9, +8.1) %predicted. CONCLUSIONS: Real-world changes in LCI2.5 (-0.7) are different to those reported in clinical trials (-2.29). Lower baseline LCI2.5 as a result of prior modulator exposure, high baseline lung health, and new LCI2.5 software analyses all contribute to lower LCI2.5 values being recorded in the real world of children with CF.

Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks.

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.

The clinical impact of serious respiratory disease in children under the age of two years during the 2021-2022 bronchiolitis season in England, Scotland and Ireland.

BACKGROUND: Interventions introduced to reduce the spread of SARS-CoV-2 led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. METHODS: We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection or first episode of wheeze to 59 Emergency Departments across England, Scotland and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. RESULTS: The BronchStart study collected data on 17,899 presentations for 17,164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1,907/3,912 (48.7%) tested positive. We estimate that every year in England and Scotland 28,561 (95% confidence interval 27,637-29,486) infants are admitted with RSV infection. CONCLUSIONS: RSV infection was the main cause of hospitalisations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Background: Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Methods: Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. Results: We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. Discussion: If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. Conclusion: s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.

Near-fatal and fatal asthma and air pollution: are we missing an opportunity to ask key questions?

There is an increasing body of evidence supporting the link between asthma attacks and air pollution in children. To our knowledge, there has only been one reported case of a fatal asthma attack in a child associated with air pollution and this was in the UK. This article considers why there is a lack of evidence on fatal/near-fatal asthma and air pollution. We also explore three challenges. First, fatal and near-fatal asthma events are rare and not yet well understood. Second, measuring and interpreting personal exposure to air pollution with sufficient temporal and spatial detail are challenging to interpret in the context of individual fatal or near-fatal asthma attacks. Third, current studies are not designed to answer the question of whether or to what extent air pollution is associated with fatal/near-fatal asthma attacks in children. Conclusive evidence is not yet available and systems of data collection for both air pollution and fatal and near-fatal asthma attacks should be enhanced to ensure risk can be determined and impact minimised.

Multi-Modal Portable Respiratory Rate Monitoring Device for Childhood Pneumonia Detection.

Accurate assessment of Respiratory Rate (RR) is the most important mechanism in detecting pneumonia in low-resource settings. Pneumonia is a disease with one of the highest mortality rates among young children under five. However, the diagnosis of pneumonia for infants remains challenging, especially in low- and middle-income countries (LMIC). In such situations, RR is most often measured manually with visual inspection. Accurate RR measurement requires the child to remain calm without any stress for a few minutes. The difficulty in achieving this with a sick child in a clinical environment can result in errors and misdiagnosis, even more so when the child is crying and non-cooperating around unfamiliar adults. Therefore, we propose an automated novel RR monitoring device built with textile glove and dry electrodes which can make use of the relaxed posture when the child is resting on the carer's lap. This portable system is non-invasive and made with affordable instrumentation integrated on customized textile glove. The glove has multi-modal automated RR detection mechanism that simultaneously uses bio-impedance and accelerometer data. This novel textile glove with dry electrodes can easily be worn by a parent/carer and is washable. The real-time display on a mobile app shows the raw data and the RR value, allowing a healthcare professional to monitor the results from afar. The prototype device has been tested on 10 volunteers with age variation of 3 years to 33 years, including male and female. The maximum variation of measured RR with the proposed system is ±2 compared to the traditional manual counting method. It does not create any discomfort for either the child or the carer and can be used up to 60 to 70 sessions/day before recharging.

Feasibility and acceptability of bubble continuous positive airway pressure oxygen therapy for the treatment of childhood severe pneumonia and hypoxaemia in Bangladeshi children.

Background: Effective management of hypoxaemia is key to reducing pneumonia deaths in children. In an intensive care setting within a tertiary hospital in Bangladesh, bubble continuous positive airway pressure (bCPAP) oxygen therapy was beneficial in reducing deaths in this population. To inform a future trial, we investigated the feasibility of introducing bCPAP in this population in non-tertiary/district hospitals in Bangladesh. Methods: We conducted a qualitative assessment using a descriptive phenomenological approach to understand the structural and functional capacity of the non-tertiary hospitals (Institute of Child and Mother Health and Kushtia General Hospital) for the clinical use of bCPAP. We conducted interviews and focus group discussions (23 nurses, seven physicians, 14 parents). We retrospectively (12 months) and prospectively (three months) measured the prevalence of severe pneumonia and hypoxaemia in children attending the two study sites. For the feasibility phase, we enrolled 20 patients with severe pneumonia (age two to 24 months) to receive bCPAP, putting in place safeguards to identify risk. Results: Retrospectively, while 747 of 3012 (24.8%) children had a diagnosis of severe pneumonia, no pulse oxygen saturation information was available. Of 3008 children prospectively assessed with pulse oximetry when attending the two sites, 81 (3.7%) had severe pneumonia and hypoxaemia. The main structural challenges to implementation were the inadequate number of pulse oximeters, lack of power generator backup, high patient load with an inadequate number of hospital staff, and inadequate and non-functioning oxygen flow meters. Functional challenges were the rapid turnover of trained clinicians in the hospitals, limited post-admission routine care for in-patients by hospital clinicians due to their extreme workload (particularly after official hours). The study implemented a minimum of four hourly clinical reviews and provided oxygen concentrators (with backup oxygen cylinders), and automatic power generator backup. Twenty children with a mean age of 6.7 (standard deviation (SD) = 5.0)) months with severe pneumonia and hypoxaemia (median (md) SpO2 = 87% in room air, interquartile range (IQR) = 85-88)) with cough (100%) and severe respiratory difficulties (100%) received bCPAP oxygen therapy for a median of 16 hours (IQR = 6-16). There were no treatment failures or deaths. Conclusions: Implementation of low-cost bCPAP oxygen therapy is feasible in non-tertiary/district hospitals when additional training and resources are allocated.

Economic burden and health-related quality-of-life among infants with respiratory syncytial virus infection: A multi-country prospective cohort study in Europe.

BACKGROUND: Respiratory syncytial virus (RSV) causes a considerable disease burden in young children globally, but reliable estimates of RSV-related costs and health-related quality-of-life (HRQoL) are scarce. This study aimed to evaluate the RSV-associated costs and HRQoL effects in infants and their caregivers in four European countries. METHODS: Healthy term-born infants were recruited at birth and actively followed up in four European countries. Symptomatic infants were systematically tested for RSV. Caregivers recorded the daily HRQoL of their child and themselves, measured by a modified EQ-5D with Visual Analogue Scale, for 14 consecutive days or until symptoms resolved. At the end of each RSV episode, caregivers reported healthcare resource use and work absenteeism. Direct medical costs per RSV episode were estimated from a healthcare payer's perspective and indirect costs were estimated from a societal perspective. Means and 95% confidence intervals (CI) of direct medical costs, total costs (direct costs + productivity loss) and quality-adjusted life-day (QALD) loss per RSV episode were estimated per RSV episode, as well as per subgroup (medical attendance, country). RESULTS: Our cohort of 1041 infants experienced 265 RSV episodes with a mean symptom duration of 12.5 days. The mean (95% CI) cost per RSV episode was €399.5 (242.3, 584.2) and €494.3 (317.7, 696.1) from the healthcare payer's and societal perspective, respectively. The mean QALD loss per RSV episode of 1.9 (1.7, 2.1) was independent of medical attendance (in contrast to costs, which also differed by country). Caregiver and infant HRQoL evolved similarly. CONCLUSION: This study fills essential gaps for future economic evaluations by prospectively estimating direct and indirect costs and HRQoL effects on healthy term infants and caregivers separately, for both medically attended (MA) and non-MA laboratory-confirmed RSV episodes. We generally observed greater HRQoL losses than in previous studies which used non-community and/or non-prospective designs.

The ability of non-physician health workers to identify chest indrawing to detect pneumonia in children below five years of age in low- and middle-income countries: A systematic review and meta-analysis.

Background: Non-physician health workers play a vital role in diagnosing and treating pneumonia in children in low- and middle-income countries (LMICs). Chest indrawing is a key indicator for pneumonia diagnosis, signifying the severity of the disease. We conducted this systematic review to summarize the evidence on non-physician health workers' ability to identify chest indrawing to detect pneumonia in children below five years of age in LMICs. Methods: We comprehensively searched four electronic databases, including MEDLINE, Embase, Web of Science, and Scopus, and reference lists from the identified studies, from January 1, 1990, to January 20, 2022, with no language restrictions. Studies evaluating the performance of non-physician health workers in identifying chest indrawing compared to a reference standard were included. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess the methodological quality of the selected studies and conducted a meta-analysis following a bivariate random effects model to estimate the pooled sensitivity and specificity. Results: We identified nine studies covering 4468 children that reported the accuracy of a non-physician health worker in identifying chest indrawing. Most studies were conducted in the 1990s, based at health facility settings, with children aged 2-59 months, and with pediatricians/physicians as the reference standard. Using the QUADAS-2, we evaluated most studies as having a low risk of bias and a low concern regarding applicability in all domains. The median sensitivity, specificity, positive predictive value, and negative predictive value were 44%, 97%, 55%, and 95%, respectively. We selected five studies for the meta-analysis. The pooled sensitivity was 46% (95% confidence interval (CI) = 37-56), and the pooled specificity was 95% (95% CI = 91-97). Conclusions: We found the ability of non-physician health workers in LMICs in identifying chest indrawing pneumonia is relatively poor. Appropriate measures, such as targeted identification and training, supportive supervision, regular performance assessment, and feedback for those who have a poor ability to recognize chest indrawing, should be taken to improve the diagnosis of pneumonia in children. New studies are needed to assess the new generation of health workers. Registration: PROSPERO (CRD42022306954).

Exercise as airway clearance therapy (ExACT) in cystic fibrosis: a UK-based e-Delphi survey of patients, caregivers and health professionals.

Replacing traditional airway clearance therapy (tACT) with exercise (ExACT) in people with cystic fibrosis (pwCF) is a top research priority. A UK-based e-Delphi consensus was performed to inform the type(s), duration and intensity of ExACT. The expert panel comprised CF physiotherapists, doctors, pwCF and parents/partners. Exercise ACT was considered to be aerobic activity, of at least 20 min duration and intense enough to elicit deep breathing. Consensus was reached that assessment breaths, coughs and huffs should accompany exercise to remove loose secretions, with support for trials to investigate ExACT versus tACT during times of stable disease but not pulmonary exacerbations.

Socioeconomic position, bronchiolitis and asthma in children: counterfactual disparity measures from a national birth cohort study.

BACKGROUND: The debated link between severe respiratory syncytial virus (RSV) infection in early life and asthma has yet to be investigated within a social inequity lens. We estimated the magnitude of socioeconomic disparity in childhood asthma which would remain if no child were admitted to hospital for bronchiolitis, commonly due to RSV, during infancy. METHODS: The cohort, constructed from national administrative health datasets, comprised 83853 children born in Scotland between 1 January 2007 and 31 June 2008. Scottish Index for Multiple Deprivation (SIMD) was used to capture socioeconomic position. Emergency admissions for bronchiolitis before age 1 year were identified from hospital records. Yearly indicators of asthma/wheeze from ages 2 to 9 years were created using dispensing data and hospital admission records. RESULTS: Using latent class growth analysis, we identified four trajectories of asthma/wheeze: early-transient (2.2% of the cohort), early-persistent (2.0%), intermediate-onset (1.8%) and no asthma/wheeze (94.0%). The estimated marginal risks of chronic asthma (combining early-persistent and intermediate-onset groups) varied by SIMD, with risk differences for the medium and high deprivation groups, relative to the low deprivation group, of 7.0% (95% confidence interval: 3.7-10.3) and 13.0% (9.6-16.4), respectively. Using counterfactual disparity measures, we estimated that the elimination of bronchiolitis requiring hospital admission could reduce these risk differences by 21.2% (4.9-37.5) and 17.9% (10.4-25.4), respectively. CONCLUSIONS: The majority of disparity in chronic asthma prevalence by deprivation level remains unexplained. Our paper offers a guide to using causal inference methods to study other plausible pathways to inequities in asthma using complex, linked administrative data.

The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available. METHODS: We performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572. FINDINGS: In total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0-28·6) and that of medically attended RSV infection was 14·1% (12·3-16·0). INTERPRETATION: RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.

Developing a video expert panel as a reference standard to evaluate respiratory rate counting in paediatric pneumonia diagnosis: protocol for a cross-sectional study.

INTRODUCTION: Manual counting of respiratory rate (RR) in children is challenging for health workers and can result in misdiagnosis of pneumonia. Some novel RR counting devices automate the counting of RR and classification of fast breathing. The absence of an appropriate reference standard to evaluate the performance of these devices is a challenge. If good quality videos could be captured, with RR interpretation from these videos systematically conducted by an expert panel, it could act as a reference standard. This study is designed to develop a video expert panel (VEP) as a reference standard to evaluate RR counting for identifying pneumonia in children. METHODS AND ANALYSIS: Using a cross-sectional design, we will enrol children aged 0-59 months presenting with suspected pneumonia at different levels of health facilities in Dhaka and Sylhet, Bangladesh. We will videorecord a physician/health worker counting RR manually and also using an automated RR counter (Children's Automated Respiration Monitor) from each child. We will establish a standard operating procedure for capturing quality videos, make a set of reference videos, and train and standardise the VEP members using the reference videos. After that, we will assess the performance of the VEP as a reference standard to evaluate RR counting. We will calculate the mean difference and proportions of agreement within±2 breaths per minute and create Bland-Altman plots with limits of agreement between VEP members. ETHICS AND DISSEMINATION: The study protocol was approved by the National Research Ethics Committee of Bangladesh Medical Research Council, Bangladesh (registration number: 39315022021) and Edinburgh Medical School Research Ethics Committee (EMREC), Edinburgh, UK (REC Reference: 21-EMREC-040). Dissemination of the study findings will be through conference presentations and publications in peer-reviewed scientific journals.

Introducing pulse oximetry for outpatient management of childhood pneumonia: An implementation research adopting a district implementation model in selected rural facilities in Bangladesh.

Background: Pulse oximetry has potential for identifying hypoxaemic pneumonia and substantially reducing under-five deaths in low- and middle-income countries (LMICs) setting. However, there are few examples of introducing pulse oximetry in resource-constrained paediatric outpatient settings, such as Integrated Management of Childhood Illness (IMCI) services. Methods: The National IMCI-programme of Bangladesh designed and developed a district implementation model for introducing pulse oximetry in routine IMCI services through stakeholder engagement and demonstrated the model in Kushtia district adopting a health system strengthening approach. Between December 2020 and June 2021, two rounds of assessment were conducted based on WHO's implementation research framework and outcome variables, involving 22 IMCI service-providers and 1680 children presenting with cough/difficulty-in-breathing in 12 health facilities. The data collection procedures included structured-observations, re-assessments, interviews, and data-extraction by trained study personnel. Findings: We observed that IMCI service-providers conducted pulse oximetry assessments on all eligible children in routine outpatient settings, of which 99% of assessments were successful; 85% (95% CI 83,87) in one attempt, and 69% (95% CI 67,71) within one minute. The adherence to standard operating procedure related to pulse oximetry was 92% (95% CI 91,93), and agreement regarding identifying hypoxaemia was 97% (95% CI 96,98). The median performance-time was 36 seconds (IQR 20,75), which was longer among younger children (2-11 months: 44s, IQR 22,78; 12-59 months: 30s, IQR 18,53, p < 0.01) and among those classified as pneumonia/severe-pneumonia than as no-pneumonia (41s, IQR 22,70; 32s, IQR 20,62, p < 0.01). We observed improvements in almost all indicators in round-2. IMCI service-providers and caregivers showed positive attitudes towards using this novel technology for assessing their children. Interpretation: This implementation research study suggested the adoption, feasibility, fidelity, appropriateness, acceptability, and sustainability of pulse oximetry introduction in routine IMCI services in resource-poor settings. The learning may inform the evidence-based scale-up of pulse oximetry linked with an oxygen delivery system in Bangladesh and other LMICs. Funding: This research was funded by the UK National Institute for Health Research (NIHR) (Global Health Research Unit on Respiratory Health (RESPIRE); 16/136/109) using UK aid from the UK Government to support global health research.

Success and time implications of SpO2 measurement through pulse oximetry among hospitalised children in rural Bangladesh: Variability by various device-, provider- and patient-related factors.

Background: Hypoxaemia is one of the strongest predictors of mortality among children with pneumonia. It can be identified through pulse oximetry instantaneously, which is a non-invasive procedure but can be influenced by factors related to the specific measuring device, health provider and patient. Following WHO's global recommendation in 2014, Bangladesh decided to introduce pulse oximetry in paediatric outpatient services, ie, the Integrated Management of Childhood Illness (IMCI) services in 2019. A national committee updated the existing IMCI implementation package and decided to test it by assessing the pulse oximetry performance of different types of assessors in real-life inpatient settings. Methods: We adopted an observational design and conducted a technology assessment among children admitted to a rural district hospital. Eleven nurses and seven paramedics received one-day training on pulse oximetry as assessors. Each assessor performed at least 30 pulse oximetry measurements on children with two types of handheld devices. The primary outcome of interest was obtaining a successful measurement of SpO2, defined as observing a stable (±1%) reading for at least 10 seconds. Performance time, ie, time taken to obtain a successful measurement of SpO2 was considered the secondary outcome of interest. In addition, we used Generalized Estimating Equation to assess the effect of different factors on the pulse oximetry performance. Results: The assessors obtained successful measurements of SpO2 in all attempts (n = 1478) except one. The median time taken was 30 (interquartile range (IQR) = 22-42) seconds, and within 60 seconds, 92% of attempts were successful. The odds of obtaining a successful measurement within 60 seconds were 7.3 (95% confidence interval (CI) = 3.7-14.2) times higher with a Masimo device than a Lifebox device. Similarly, assessors aged >25 years were 4.8 (95% CI = 1.2, 18.6) times more likely to obtain a successful measurement within 60 seconds. The odds of obtaining a successful measurement was 2.6 (95% CI = 1.6, 4.2) times higher among children aged 12-59 months compared to 2-11 months. Conclusions: Our study indicated that assessors could achieve the necessary skills to perform pulse oximetry successfully in real-life inpatient settings through a short training module, with some effect of device-, provider- and patient-related factors. The National IMCI Programme of Bangladesh can use these findings for finalising the national IMCI training modules and implementation package incorporating the recommendation of using pulse oximetry for childhood pneumonia assessment.