Comparison of paediatric infectious disease deaths in public sector health facilities using different data sources in the Western Cape, South Africa (2007-2021).

BACKGROUND: Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources. METHODS: The three data sources: RHIS, Child PIP, and DN Surveillance are integrated and linked by the Western Cape Provincial Health Data Centre using a unique patient identifier. We calculated the deduplicated total number of infectious disease deaths and estimated admission mortality rates using all three data sources. We determined the completeness of Child PIP and DN Surveillance in identifying deaths recorded in RHIS and the level of agreement for causes of death between data sources. RESULTS: Completeness of recorded in-facility infectious disease deaths in Child PIP (23/05/2007-08/02/2021) and DN Surveillance (2010-2013) was 70% and 69% respectively. The greatest agreement in infectious causes of death were for diarrhoea and LRTI: 92% and 84% respectively between RHIS and Child PIP, and 98% and 83% respectively between RHIS and DN Surveillance. In-facility infectious disease admission mortality rates decreased significantly for the province: 1.60 (95% CI: 1.37-1.85) to 0.73 (95% CI: 0.56-0.93) deaths per 1000 live births from 2007 to 2020. CONCLUSION: RHIS had accurate causes of death amongst children dying from infectious diseases, particularly for diarrhoea and LRTI, with declining in-facility admission mortality rates over time. We recommend integrating data sources to ensure the most accurate assessment of child deaths.

Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial).

BACKGROUND: Late onset sepsis is a leading cause of death and morbidity in preterm infants. Despite optimal antibiotic treatment, sepsis related mortality and morbidity is still high. Pentoxifylline (PTX) is a methylxanthine with promising immunomodulatory properties, which can be used as an additional therapy next to antibiotics in preterm infants. PTX is increasingly used off-label in neonatal intensive care units, however up till now no dose finding study has been done for PTX in this specific population. The aim of this study (PTX-trial) is to determine the optimal dose of PTX in preterm infants (gestational age < 30 weeks) with (suspected) late onset sepsis. Dose finding in this particular population is unique, since for most drugs used in neonates the optimal dosage has not been investigated in phase II dose-seeking studies. METHODS: The PTX-trial is a prospective open label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design will be used, with dose step-up and step-down titration after every 3 patients. The PTX starting dosage will be 30 mg/kg/day in 6 hours as described in most previous neonatal studies. Efficacy is defined by means of biochemical and clinical parameters. Toxicity in these vulnerable patients is unwarranted. The optimal dose is defined as the ED75 (i.e., clinically and chemically effective dose for 75% of patients) in preterm neonates with late onset sepsis. We plan to include 30 neonates to determine the optimal dose using this study design. Subsequently, the optimal dose will be validated in 10 additional preterm neonates. In parallel, pharmacokinetics of PTX and its metabolites will be described as well as longitudinal evaluation of metabolomics and proteomics. DISCUSSION: The study has been approved by the Regional Medical Ethics Board of Erasmus Medical Center University Rotterdam (MEC 2019-0477) and registered at Clinicaltrials.gov (NCT04152980). Results of the main trial and each of the secondary endpoints will be submitted for publications in peer-reviewed journals. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04152980 , Registered November 6th, 2019.

Is health expenditure on immunisation associated with immunisation coverage in sub-Saharan Africa? A multicountry analysis, 2013-2017.

OBJECTIVES: The designing of contextually tailored sustainable plans to finance the procurement of vaccines and the running of appropriate immunisation programmes are necessary to address the high burden of vaccine-preventable diseases and low immunisation coverage in sub-Saharan Africa (SSA). We sought to estimate the minimum fraction of a country's health budget that should be invested in national immunisation programmes to achieve national immunisation coverage of 80% or greater depending on the context, with and without donors' support. DESIGN: Multicountry analysis of secondary data using retrieved publicly available data from the WHO, Global Alliance for Vaccines and Immunization (GAVI) and World Bank databases. SETTING: Data on 24 SSA countries, between 2013 and 2017. METHODS: We model the variations in immunisation coverage across the different SSA countries using a fractional logit model. Three different generalised linear models were fitted to explore how various explanatory variables accounted for the variability in each of the three different vaccines-measles-containing vaccine (MCV)1, diphtheria, pertussis, tetanus (DPT3) and BCG. RESULTS: We observed an association between current health expenditure (as a percentage of gross domestic product) and immunisation coverage for BCG (OR=1.01, 95% CI: 1.01 to 1.04, p=0.008) and DPT3 (OR=1.01, 95% CI: 1.0 to 1.02, p=0.020) vaccines. However, there was no evidence to indicate that health expenditure on immunisation (as a proportion of current health expenditure) could be a strong predictor of immunisation coverage (DPT, OR 0.96 (95% CI 0.78 to 1.19; p=0.702); BCG, OR 0.91 (0.69 to 1.19; p=0.492); MCV, OR 0.91 (0.69 to 1.19; p=0.482)). We demonstrate in selected countries that to achieve the GAVI target of 80% in the countries with low DPT3 coverage, health expenditure would need to be increased by more than 45%. CONCLUSIONS: There is a need to facilitate the development of strategies that support African countries to increase domestic financing for national immunisation programmes towards achieving 2030 targets for immunisation coverage.

Developing films to support vaccine-hesitant, ethnically diverse parents' decision-making about the human papillomavirus (HPV) vaccine: a codesign study.

OBJECTIVE: To illustrate an evidence-, theory- and person-based approach to codesign the COMMUNICATE films that support parental decision-making about the human papillomavirus (HPV) vaccine for their teenagers. DESIGN: Codesign study. SETTING: Localities covered by two immunisation teams in London and the south-west of England. METHODS: The intervention planning phase involved combining evidence from a literature review with qualitative interview data to identify barriers and facilitators to HPV vaccine uptake, as well as design features that should be incorporated within the COMMUNICATE films. The intervention development phase involved identifying guiding principles for the COMMUNICATE films, mapping behaviour change techniques onto the behaviour change wheel and codesigning the COMMUNICATE films. Feedback from users informed modifications to maximise acceptability and feasibility and to support behaviour change. RESULTS: The primary and secondary evidence highlighted important content to include within the COMMUNICATE films: emphasise the benefits of the HPV vaccine, provide transparent information about the safety profile and side effects and emphasise the universality and commonality of HPV infection. A series of scripts were used to guide 4 film shoots to create the content in multiple community languages with 16 participants, including vaccine-hesitant, ethnically diverse parents and professionals. Overall, participants were positive about the films. Potential messengers and ways the films could be distributed, identified by parents, include local social media networks or text messages from general practices. The need for information about the HPV vaccine to be shared by schools ahead of consent being sought was also raised. CONCLUSIONS: By using an integrated approach to intervention development, this study has begun to address the need for an intervention to support vaccine-hesitant, ethnically diverse parents' decision-making about the HPV vaccination programme. A future study to codesign, implement and evaluate a communication strategy for the COMMUNICATE films is planned.

High-resolution mapping of essential maternal and child health service coverage in Nigeria: a machine learning approach.

BACKGROUND: National-level coverage estimates of maternal and child health (MCH) services mask district-level and community-level geographical inequities. The purpose of this study is to estimate grid-level coverage of essential MCH services in Nigeria using machine learning techniques. METHODS: Essential MCH services in this study included antenatal care, facility-based delivery, childhood vaccinations and treatments of childhood illnesses. We estimated generalised additive models (GAMs) and gradient boosting regressions (GB) for each essential MCH service using data from five national representative cross-sectional surveys in Nigeria from 2003 to 2018 and geospatial socioeconomic, environmental and physical characteristics. Using the best-performed model for each service, we map predicted coverage at 1 km2 and 5 km2 spatial resolutions in urban and rural areas, respectively. RESULTS: GAMs consistently outperformed GB models across a range of essential MCH services, demonstrating low systematic prediction errors. High-resolution maps revealed stark geographic disparities in MCH service coverage, especially between rural and urban areas and among different states and service types. Temporal trends indicated an overall increase in MCH service coverage from 2003 to 2018, although with variations by service type and location. Priority areas with lower coverage of both maternal and vaccination services were identified, mostly located in the northern parts of Nigeria. CONCLUSION: High-resolution spatial estimates can guide geographic prioritisation and help develop better strategies for implementation plans, allowing limited resources to be targeted to areas with lower coverage of essential MCH services.

Coutilisation of oral rehydration solution and zinc for treating diarrhoea and its associated factors among under-five children in East Africa: a multilevel robust Poisson regression.

OBJECTIVE: This study aimed to assess the coutilisation of oral rehydration solution (ORS) and zinc for treating diarrhoea and its associated factors among under-5 children in East Africa. DESIGN: Cross-sectional study design. Multilevel Poisson regression analysis with robust variance was fitted to identify predictors of zinc and ORS coutilisation. An adjusted prevalence ratio (aPR) with a 95% CI was reported to declare the statistical significance. SETTING: Twelve East African countries. PARTICIPANTS: 16 850 under-5 children who had diarrhoea were included in the study. RESULT: In East African nations, the coutilisation of ORS and zinc for the treatment of diarrhoea in children under 5 was 53.27% with a 95% CI (52.54% to 54.01%). Children of mothers with primary education (aPR 1.15, 95% CI 1.09 to 1.20), secondary education (aPR 1.08, 95% CI 1.02 to 1.14), higer education (aPR 1.19, 95% CI 1.10 to 1.29), those from maternal age category of 20-24 (aPR 1.14, 95% CI 1.07 to 1.21), age category of 25-29 (aPR 1.13, 95% CI 1.06 to 1.21), age category of 30-34 (aPR 1.09, 95% CI 1.02 to 1.16), those from wealthy households (aPR 1.04, 95% CI 1.01 to 1.09) and those who have a media exposure (aPR 1.04, 95% CI 1.01 to 1.08) were more likely to receive combination. CONCLUSION: Only half of the under-5 children with diarrhoea in East Africa were treated with a combination of ORS and zinc. To increase the use of the suggested combination therapy of ORS with zinc, it is important to empower women through education and prevent teen pregnancy.

Cohort profile: Rahima Moosa Mother and Child Hospital maternal HIV cohort, Johannesburg, South Africa.

PURPOSE: The Rahima Moosa Mother and Child Hospital (RMMCH) maternal HIV cohort originated from data systems that were developed to support HIV-related birth care and track outcomes of a complete birth cohort of HIV-exposed infants at Rahima Moosa Hospital and their mothers living with HIV. PARTICIPANTS: Supported by the Empilweni Services and Research Unit, maternal and infant data from 13 654 pregnant women living with HIV who delivered their infants (and a subset also attended antenatal care) were collected at RMMCH in Johannesburg, South Africa since 2013. Maternal data were collected using counsellor-administered interviews and the 2013-2018 subset of this cohort was linked to the National Health Laboratory Services (NHLS) national HIV cohort-a longitudinal cohort of people living with HIV accessing care in the public sector antiretroviral therapy programme in South Africa that can observe national access to HIV care through laboratory testing data. FINDINGS TO DATE: Topics addressed by the cohort include antenatal care history, HIV treatment exposure, delivery/birth management, prophylaxis and maternal blood results relevant to HIV captured at delivery. The cohort was also one of the first to describe implementation of early infant diagnosis procedures in South Africa including evaluations of novel point-of-care testing strategies demonstrating improvements in uptake of HIV care among infants accessing point-of-care services. FUTURE PLANS: Annual linkage of infant delivery and testing data to longitudinal laboratory test data in the NHLS national HIV cohort is planned to allow for analysis of both infant continuity of care outcomes and as well as evaluation of maternal-infant pair treatment and mobility outcomes in the post partum and later period.

Effective interventions for improving routine childhood immunisation in low and middle-income countries: a systematic review of systematic reviews.

OBJECTIVE: An umbrella review providing a comprehensive synthesis of the interventions that are effective in providing routine immunisation outcomes for children in low and middle-income countries (L&MICs). DESIGN: A systematic review of systematic reviews, or an umbrella review. DATA SOURCES: We comprehensively searched 11 academic databases and 23 grey literature sources. The search was adopted from an evidence gap map on routine child immunisation sector in L&MICs, which was done on 5 May 2020. We updated the search in October 2021. ELIGIBILITY CRITERIA: We included systematic reviews assessing the effectiveness of any intervention on routine childhood immunisation outcomes in L&MICs. DATA EXTRACTION AND SYNTHESIS: Search results were screened by two reviewers independently applying predefined inclusion and exclusion criteria. Data were extracted by two researchers independently. The Specialist Unit for Review Evidence checklist was used to assess review quality. A mixed-methods synthesis was employed focusing on meta-analytical and narrative elements to accommodate both the quantitative and qualitative information available from the included reviews. RESULTS: 62 systematic reviews are included in this umbrella review. We find caregiver-oriented interventions have large positive and statistically significant effects, especially those focusing on short-term sensitisation and education campaigns as well as written messages to caregivers. For health system-oriented interventions the evidence base is thin and derived from narrative synthesis suggesting positive effects for home visits, mixed effects for pay-for-performance schemes and inconclusive effects for contracting out services to non-governmental providers. For all other interventions under this category, the evidence is either limited or not available. For community-oriented interventions, a recent high-quality mixed-methods review suggests positive but small effects. Overall, the evidence base is highly heterogenous in terms of scope, intervention types and outcomes. CONCLUSION: Interventions oriented towards caregivers and communities are effective in improving routine child immunisation outcomes. The evidence base on health system-oriented interventions is scant not allowing us to reach firm conclusions, except for home visits. Large evidence gaps exist and need to be addressed. For example, more high-quality evidence is needed for specific caregiver-oriented interventions (eg, monetary incentives) as well as health system-oriented (eg, health workers and data systems) and community-oriented interventions. We also need to better understand complementarity of different intervention types.

Challenges and support experienced by family caregivers seeking antiretroviral therapy services for children living with HIV/AIDS: a phenomenological study in Ghana.

BACKGROUND: Family caregivers of children living with HIV/AIDS in most cases are found to be overwhelmed and under-resourced, yet they are believed to be the primary source of support for children living with HIV/AIDS. Family caregivers experience different challenges that affect their children's antiretroviral therapy (ART) adherence. AIM: This study explored the lived experiences of family caregivers of children living with HIV/AIDS who sought ART services for these children at the St Joseph's Hospital of Jirapa, Ghana. METHOD: Using a qualitative phenomenology design and a semistructured in-depth interview guide and using purposive sampling, data were gathered from 13 family caregivers of children living with HIV/AIDS receiving ART treatment at St Joseph's Hospital, Jirapa following ethical approval. All interviews were audio-taped and transcribed verbatim. Reflexive thematic analysis was used to analyse the transcribed data. FINDINGS: Six themes were generated: five challenges and one support. Family caregivers of children living with HIV/AIDS experienced: (1) Financial challenges, (2) Human-related challenges, (3) Challenges at HIV testing and counselling (HTC) centres, (4) Challenges with transportation, (5) Challenges in disclosing children's HIV status to them and (6) Support received from HTC and their family members. CONCLUSION AND RECOMMENDATION: Family caregivers of children living with HIV/AIDS experience daunting challenges in their quest to care for their children. Governmental and non-governmental HIV/AIDS programme support should include small business skills training and acquisition including capital to help set up small-scale businesses for such caregivers to reduce their financial challenges. Access to ART at clinics closer to caregivers is also key to promoting adherence. Family and community support has been recognised as key to enhancing ART adherence. Education of caregivers on policy regarding disclosure of the HIV/AIDS status of children, the need to work to reduce the time spent by caregivers at HTC, and ensuring privacy by limiting access to HTCs to only caregivers and their children, are important to enhancing adherence.

Risk of transmission of HIV to infants during breast/chest feeding when mothers/birthing parents living with HIV are on antiretroviral therapy: a protocol for a rapid review.

INTRODUCTION: HIV is a major public health issue affecting millions globally. Women and girls account for 46% of new HIV infections in 2022 and approximately 1.3 million females become pregnant every year. Vertical transmission of HIV from persons living with HIV (PLHIV) to infants may occur through different modalities, such as through breast/chest feeding. Notably, 82% of PLHIV who chose to breast/chest feed are on antiretroviral therapy (ART) when feeding their infants. Precise estimates of the risk of postpartum transmission to infants during breast/chest feeding at varying viral load levels remain a significant gap in the literature. METHODS AND ANALYSIS: A rapid systematic search of electronic databases will be conducted from January 2005 to the present, including Medline, Embase and Global Health. The objective of this rapid review is to explore and assess the available evidence on the effect of varying viral load levels on the risk of HIV transmission to infants during breast/chest feeding when the birthing or gestational parent living with HIV is on ART. Study characteristics will be summarised and reported to support the narrative summary of the findings. The focus will be on the absolute risk of HIV transmission from birthing parent to infant during chest/breast feeding. The findings will also be stratified by month, including the risk of HIV transmission for 6 months and greater than 6 months postpartum. We will ascertain the risk of bias using A Measurement Tool to Assess Systematic Reviews 2, Quality of Prognosis Studies and Downs and Black checklist for the appropriate study type. A summary score will not be calculated, rather the strengths and limitations of the studies will be narratively described. ETHICS AND DISSEMINATION: No human subjects will be involved in the research. The findings of this rapid review will inform a future systematic review and will be disseminated through peer-reviewed publications, presentations and conferences. PROSPERO REGISTRATION NUMBER: CRD42024499393.

Cohort profile: longitudinal and population comparison of children who are HIV-exposed uninfected and children who are HIV unexposed in Kenya (HOPE study).

PURPOSE: Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of the impact of HIV and recent antiretroviral therapy regimen exposure on neurodevelopmental, hearing and mental health outcomes from infancy to adolescence. PARTICIPANTS: The study includes a prospective mother-infant cohort and cross-sectional child/youth-caregiver cohorts conducted in Kenya.Between 2021 and 2022, the study enrolled 2000 mother-infant pairs (1000 HEU and 1000 HIV-unexposed uninfected (HUU)) for longitudinal follow-up. Infants were eligible if they were aged 4-10 weeks and healthy. Mothers were eligible if their HIV status was known and were ≥18 years. Study visits are 6 monthly until the child reaches age 3 years.Cross-sectional cohorts spanning ages 3-18 years started enrolment in 2022. Target enrolment is 4400 children/youth (4000 HEU and 400 HUU). Children and youth are eligible if they are HIV negative, maternal HIV status and timing of diagnosis is known, and caregivers are ≥18 years.Data on infant/child/youth growth, neurodevelopment, mental health, morbidity and hearing are collected at enrolment using standardised tools. Dry blood spots samples are collected for telomere length assessment at baseline and yearly for the longitudinal cohort. Growth z-scores, neurodevelopmental scores, telomere length and prevalence of developmental and hearing problems will be compared between HEU/HUU populations. FINDINGS TO DATE: Full cohort enrolment for the longitudinal cohort is complete and participants are in follow-up. At 1 year of age, comparing HEU to HUU neurodevelopment using the Malawi developmental assessment tool, we found that HEU infants had higher language scores and comparable scores in fine motor, gross motor and social scores. The cross-sectional cohort has enrolled over 2000 participants and recruitment is ongoing. FUTURE PLANS: Longitudinal cohort follow-up and enrolment to the cross-sectional study will be completed in June 2024.

How the COVID-19 pandemic affected infant vaccination trends in rural and urban communities in Ibadan, Nigeria: a cross-sectional study.

OBJECTIVES: This study compared the infant vaccination trends a year before and a year after the onset of the COVID-19 pandemic in selected urban and rural communities in Ibadan, Nigeria. DESIGN: This was a cross-sectional study in which data were extracted from infant vaccination records. SETTING: Two rural and three urban vaccination centres in primary health clinics at Ibadan Southeast and Olúyòlé local government areas, respectively. PARTICIPANTS: Infant vaccination records 1 year before and 1 year after the onset of the COVID-19 pandemic (March 2019-February 2020 and March 2020-February 2021, respectively). OUTCOME MEASURES: Timeliness of vaccination (vaccination taken within 2 weeks of appointment) and vaccination completion according to the Nigerian routine infant vaccination schedule. RESULTS: 2000 vaccination records were included in the study (1013 (50.6%) for male infants). 840 (42.0%) of the records were from the rural immunisation clinics. There were 1194 (59.7%) and 806 (40.3%) records from before and after the onset of the COVID-19 pandemic, respectively. Before the pandemic, birth dose vaccines were timelier among infants from urban communities, while vaccines given at 6 weeks were timelier in the rural areas. Following the onset of the pandemic, the rural communities had a higher proportion of infants with timelier and complete vaccination except for the birth dose vaccines. Overall, there was higher vaccination completion before the pandemic, and this was higher in the rural compared with the urban communities both before (54.8% vs 11.7%) and after (23.6% vs 1.0%) the onset of the pandemic. CONCLUSIONS: A decline in infant vaccination uptake, timeliness and completion persisted 1 year after the COVID-19 pandemic onset, and urban communities were more affected. More efforts are required to ensure optimal infant vaccination, especially in urban communities, to forestall outbreaks of vaccine-preventable diseases.

Spatial analysis and factors associated with low birth weight in Ghana using data from the 2017 Ghana Maternal Health Survey: spatial and multilevel analysis.

OBJECTIVE: Low birth weight (LBW) is an important indicator of newborn health and can have long-term implications for a child's development. Spatial exploratory analysis provides a toolkit to gain insight into inequalities in LBW. Few studies in Ghana have explored the spatial distribution of LBW to understand the extent of the problem geographically. This study explores individual and cluster-level distributions of LBW using spatial exploration components for common determinants from nationally representative survey data. DESIGN: We used data from the 2017 Ghana Maternal Health Survey and conducted individual-level and cluster-level analyses of LBW with place and zone of residence in both bivariate and multivariate analyses. By incorporating spatial and survey designs methodology, logistic and Poisson regression models were used to model LBW. SETTING: Ghana. PARTICIPANTS: A total of 4127 women aged between 15 and 49 years were included in the individual-level analysis and 864 clusters corresponding to birth weight. PRIMARY AND SECONDARY OUTCOME MEASURES: Individual and cluster-level distribution for LBW using spatial components for common determinants. RESULTS: In the individual-level analysis, place and zone of residence were significantly associated with LBW in the bivariate model but not in a multivariate model. Hotspot analysis indicated the presence of LBW clusters in the middle and northern zones of Ghana. Compared with rural areas, clusters in urban areas had significantly lower LBW (p=0.017). Clusters in the northern zone were significantly associated with higher LBW (p=0.018) compared with the coastal zones. CONCLUSION: Our findings from choropleth hotspot maps suggest LBW clusters in Ghana's northern and middle zones. Disparities between the rural and urban continuum require specific attention to bridge the healthcare system gap for Ghana's northern and middle zones.

Defining complicated urinary tract infection and route of antibiotics in children presenting to the emergency department: a cohort study using the Melbourne RUPERT clinical score.

OBJECTIVES: Most children with uncomplicated urinary tract infections (UTI) can be managed with oral antibiotics. However, identifying those likely to fail oral and need intravenous antibiotics due to complicating features at presentation is challenging. We aimed to derive, validate and test a score to guide initial antibiotic route. DESIGN: This cohort study enrolled children both prospectively and retrospectively. Patients were divided into two groups based on whether they received intravenous or oral antibiotics after 24 hours, including those who switched between routes. Children diagnosed with confirmed UTI were used to derive then validate the score, comparing complicating clinical features between the two groups. Combinations of significantly differentiating features generated receiver operating characteristic curves and the optimal cut-off for intravenous antibiotic use was selected. SETTING: The emergency department of a tertiary paediatric hospital. PARTICIPANTS: All children aged 3 months-17 years with suspected UTI were eligible, and were included if they fulfilled the diagnostic criteria for UTI. OUTCOME MEASURES: The effectiveness of the derived clinical score to differentiate patients at presentation who had complicated UTI requiring ongoing intravenous antibiotics. RESULTS: There were 1240 patients, of whom 167 children aged 12 months-11 years with confirmed UTI comprised the derivation cohort. The combination of features that performed optimally (area under curve 0.85, 95% CI 0.79 to 0.91) were: rigors, urological abnormality, fever (≥38°C), emesis, recurrent (≥3) UTI, tachycardia: the RUPERT score (1 point each, maximum 6). A score ≥3 accurately classified route of antibiotics after 24 hours for 80% patients (sensitivity 77%, specificity 81%). For the 168 patients in the validation cohort, the score accurately classified 76% (sensitivity 67%, specificity 78%). The score tested well in 'probable' UTI and adolescents, and less well in infants. CONCLUSION: The Melbourne RUPERT score provides the first standardised, easy-to-use score to aid clinicians in deciding route of antibiotics for more complicated UTI in children. It now needs prospective validation.

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland.

OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588.

CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Persistent symptoms and conditions among children and adolescents hospitalised with COVID-19 illness: a qualitative study.

OBJECTIVES: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection. DESIGN, SETTING AND PARTICIPANTS: A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo. RESULTS: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems. CONCLUSIONS: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities.

Multicomponent interventions to improve routine childhood vaccine uptake in low and middle-income countries: a scoping review protocol.

INTRODUCTION: Vaccine coverage remains inequitable globally. Many systematic reviews have looked at the effectiveness of strategies to improve vaccine uptake; however, these reviews frequently lack data from low and middle-income countries (LMICs), where evidence of cost-effective strategies is most valuable. This is partly because reviews often exclude non-randomised, observational or unpublished evaluations that are common in LMICs. Many reviews also exclude multicomponent interventions due to challenges isolating the effect of each component. A comprehensive mapping of multicomponent interventions implemented in LMICs would increase the visibility of studies excluded from systematic reviews and improve comparability of future evaluations by providing guidance for researchers on evaluation frameworks. This scoping review aims to identify, compare and summarise the properties and evaluation methods of multicomponent interventions to improve uptake of routine childhood vaccines in LMICs, and to assess the strengths and limitations of evaluation frameworks applied. METHODS AND ANALYSIS: This review will be conducted using the Joanna Briggs Institute methodology for scoping reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews guidelines. We will search the following databases: MEDLINE, Embase, PubMed, Cochrane, Eldis and Global Health (CAB Direct), Global Index Medicus, 3ie Portal, Google Scholar, COnnecting REpositories, and reference lists. One author will screen titles and abstracts and extract data from included articles using a pretested data extraction template. Uncertainties will be resolved through discussion with another author. Only studies published in English will be included for full review. We will assess the practicability, applicability, sensitivity and specificity of the evaluation frameworks used and present results using descriptive statistics, summary tables and charts. ETHICS AND DISSEMINATION: Ethics approval is not required. The review will be submitted as part of a doctoral thesis, presented at conferences and published in peer-reviewed journals. STUDY REGISTRATION: https://osf.io/7r84g.