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ObjectivesAlthough croup is a common respiratory illness, there is little published regarding symptom course. We aimed to assess symptom progression and caregiver burden, and whether age, sex or season and initial severity of disease are associated with symptom duration.Design, setting and participantsWe conducted a secondary analysis of two Canadian prospective cohorts of children 0–16 years old diagnosed with croup; one recruited from a paediatric emergency department (ED) (307 children) between November 1999 and March 2000, and the other from 26 general EDs (1214 children) between September 2002 and April 2006. Baseline data included age, sex, season, corticosteroid treatment and clinical severity score based on the presence or absence of a barky cough, stridor at rest or with agitation and chest wall indrawing (mild, moderate or severe). For both cohorts, the child’s primary caregiver was telephoned daily to collect symptom progression and psychosocial data (caregiver stress, lost sleep and work) until the child was symptom-free for over 24 hours.ResultsThe paediatric and general ED cohorts are reported separately; croup symptoms peaked at initial ED presentation for 96% and 77%, respectively. The longest-lived symptom was a barky cough, resolving by 34 and 47 hours for 50%, and 78 and 119 hours for 90% of children, respectively. Neither sex nor severity at presentation were significantly associated with symptom duration in either cohort. Season of illness was associated in both; age was associated in the general but not the paediatric ED cohort. The primary caregiver lost a mean (SD) of 4.1 (4.9) and 2.8 (4.7) hours of sleep during the illness.ConclusionsMost children with croup presented for care at the peak of symptom severity. Symptoms resolved for half of the children in 1.5–2 days and for 90% in 3–5 days after presentation. Caregivers experienced a significant loss of sleep.

IntroductionWard-based high-flow nasal cannula (HFNC) is an effective therapy for children with bronchiolitis who have failed standard oxygen therapy. However, HFNC can increase hospital length of stay perhaps because there is a lack of evidence to guide weaning strategies.We aim to conduct a pilot study to identify the most effective weaning strategy for infants, up to 12 months, supported on HFNC for bronchiolitis. This may lead to reduced time on respiratory support and shorter length of stay. If this pilot study is deemed feasible, it will inform a larger multicentre trial.Methods and analysisThis open label, non-blinded, randomised controlled trial will be conducted over 24 months at the Noah’s Ark Children’s Hospital for Wales, Cardiff, and will aim to recruit 20 patients. It will compare high-flow only weaning (high-flow discontinued at FiO2 of 21%) to HFNC and low-flow weaning (HFNC discontinued at 30% and replaced by low-flow up to 2 L/min). HFNC therapy will be delivered at 2 L/kg/min (maximum 20 L/min). The primary outcome is to examine the feasibility of different weaning strategies for infants with bronchiolitis requiring HFNC. Secondary outcomes include the time from decision to wean HFNC to the patient no longer requiring respiratory support and a safety assessment of the weaning strategies.Ethics and disseminationHealth Research Authority and Health and Care Research Wales approval was granted on 8 September 2020 following review by the NHS research ethics committee.The sponsor is Cardiff and Vale University Health Board. We will publish the results in a peer-reviewed medical journal, via websites and newsletters.Trial registration numberNCT04287959.

IntroductionCall and recall systems provide actionable intelligence to improve equity and timeliness of childhood vaccinations, which have been disrupted during the COVID-19 pandemic. We will evaluate the effectiveness, fidelity and sustainability of a data-enabled quality improvement programme delivered in primary care using an Active Patient Link Immunisation (APL-Imms) call and recall system to improve timeliness and equity of uptake in a multiethnic disadvantaged urban population. We will use qualitative methods to evaluate programme delivery, focusing on uptake and use, implementation barriers and service improvements for clinical and non-clinical primary care staff, its fidelity and sustainability.Methods and analysisThis is a mixed-methods observational study in 284 general practices in north east London (NEL). The target population will be preschool-aged children eligible to receive diphtheria, tetanus and pertussis (DTaP) or measles, mumps and rubella (MMR) vaccinations and registered with an NEL general practice. The intervention comprises an in-practice call and recall tool, facilitation and training, and financial incentives. The quantitative evaluation will include interrupted time Series analyses and Slope Index of Inequality. The primary outcomes will be the proportion of children receiving at least one dose of a DTaP-containing or MMR vaccination defined, respectively, as administered between age 6 weeks and 6 months or between 12 and 18 months of age. The qualitative evaluation will involve a ‘Think Aloud’ method and semistructured interviews of stakeholders to assess impact, fidelity and sustainability of the APL-Imms tool, and fidelity of the implementation by facilitators.Ethics and disseminationThe research team has been granted permission from data controllers in participating practices to use deidentified data for audit purposes. As findings will be specific to the local context, research ethics approval is not required. Results will be disseminated in a peer-reviewed journal and to stakeholders, including parents, health providers and commissioners.

IntroductionEdinburgh and Lothians’ Viral Intervention Study Kids is a parallel, open-label, randomised controlled trial of hypertonic saline (HS) nose drops (~2.6% sodium chloride) vs standard care in children <7 years of age with symptoms of an upper respiratory tract infection (URTI).Methods and analysisChildren are recruited prior to URTI or within 48 hours of developing URTI symptoms by advertising in areas such as local schools/nurseries, health centres/hospitals, recreational facilities, public events, workplaces, local/social media. Willing parents/guardians, of children <7 years of age will be asked to contact the research team at their local site. Children will be randomised to either a control arm (standard symptomatic care), or intervention arm (three drops/nostril of HS, at least four times a day, until 24 hours after asymptomatic or a maximum of 28 days). All participants are requested to provide a nasal swab at the start of the study (intervention arm: before HS drops) and then daily for four more days. Parent/guardian complete a validated daily diary, an end of illness diary, a satisfaction questionnaire and a wheeze questionnaire (day 28). The parent/guardian of a child in the intervention arm is taught to prepare HS nose drops. Parent/guardian of children asymptomatic at recruitment are requested to inform the research team within 48 hours of their child developing an URTI and follow the instructions already provided. The day 28 questionnaire determines if the child experienced a wheeze following illness. Participation in the study ends on day 28.Ethics and disseminationThe study has been approved by the West of Scotland Research Ethics Service (18/WS/0080). It is cosponsored by Academic and Clinical Central Office for Research and Development—a partnership between the University of Edinburgh and National Health Service Lothian Health Board. The findings will be disseminated through peer-reviewed publications, conference presentations and via the study website.Trial registration numberNCT03463694.

BackgroundMortality rates from cervical cancer demonstrate deep inequality in health between richer and poorer populations. Over 310 000 women died of this preventable disease in 2018, mostly in low-income and middle-income countries (LMICs) where screening and treatment are beyond the capacity of health systems. Immunisation against human papillomavirus (HPV) offers a primary prevention strategy, but rates of vaccination uptake are unclear. Understanding coverage levels and factors affecting uptake can inform immunisation strategies.ObjectivesThe aim of this study is to evaluate the status of HPV vaccination coverage from nationally reported indicators and to estimate global coverage in a single year cohort of vaccine-eligible girls.DesignThis study provides quantitative population-level estimates of important global health indicators. Using data from the Global Cancer Observatory and WHO/UNICEF, incidence of and mortality from cervical cancer and HPV vaccination coverage are described for countries, categorised by income group. Characteristics of LMICs achieving high coverage are explored using selected development indicators from World Bank sources. Global HPV immunisation coverage is calculated and its impact on cervical cancer mortality estimated.ResultsIncidence and mortality for cervical cancer correlate with poverty. Whilst all WHO member states report high infant measles vaccination rates, fewer than half report on HPV vaccination. Even amongst high-income countries, coverage varies widely. In upper-middle-income countries, there is a trend for higher coverage with increased health spending per capita. Four LMICs report good coverage levels, all associated with external funding. Global HPV immunisation coverage for 2018 is estimated at 12.2%. Of the global cohort of 61 million 15-year-old girls in 2018, 7000 are likely to die from cervical cancer, almost all in LMICs.ConclusionsCountries in all income groups must devise strategies to achieve and maintain higher levels of HPV immunisation. For all but the richest, affordability remains a barrier.

ObjectiveTo investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants.DesignA prospective observational study.SettingPublic healthcare system in Santa Clara County (California, USA).ParticipantsWomen with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021.OutcomesSARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life.ResultsOf 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60–180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1–4, 5–12, and 13–28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection.ConclusionsMaternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.

ObjectivesThe WHO currently recommends stool testing using GeneXpert MTB/Rif (Xpert) for the diagnosis of paediatric tuberculosis (TB). The simple one-step (SOS) stool method enables processing for Xpert testing at the primary healthcare (PHC) level. We modelled the impact and cost-effectiveness of implementing the SOS stool method at PHC for the diagnosis of paediatric TB in Ethiopia and Indonesia, compared with the standard of care.SettingAll children (age <15 years) presenting with presumptive TB at primary healthcare or hospital level in Ethiopia and Indonesia.Primary outcomeCost-effectiveness estimated as incremental costs compared with incremental disability-adjusted life-years (DALYs) saved.MethodsDecision tree modelling was used to represent pathways of patient care and referral. We based model parameters on ongoing studies and surveillance, systematic literature review, and expert opinion. We estimated costs using data available publicly and obtained through in-country expert consultations. Health outcomes were based on modelled mortality and discounted life-years lost.ResultsThe intervention increased the sensitivity of TB diagnosis by 19–25% in both countries leading to a 14–20% relative reduction in mortality. Under the intervention, fewer children seeking care at PHC were referred (or self-referred) to higher levels of care; the number of children initiating anti-TB treatment (ATT) increased by 18–25%; and more children (85%) initiated ATT at PHC level. Costs increased under the intervention compared with a base case using smear microscopy in the standard of care resulting in incremental cost-effectiveness ratios of US$132 and US$94 per DALY averted in Ethiopia and Indonesia, respectively. At a cost-effectiveness threshold of 0.5×gross domestic product per capita, the projected probability of the intervention being cost-effective in Ethiopia and Indonesia was 87% and 96%, respectively. The intervention remained cost-effective under sensitivity analyses.ConclusionsThe addition of the SOS stool method to national algorithms for diagnosing TB in children is likely to be cost-effective in both Ethiopia and Indonesia.

ObjectivesTo identify the risk factors for neonatal sepsis in Sub-Saharan Africa.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Web of Science, African Index Medicus and ClinicalTrials.gov were searched for observational studies from January 2010 to August 2020.SettingSub-Saharan Africa, at all levels of healthcare facilities.Participants‘Neonates’ (<28 days of age) at risk of developing either clinical and/or laboratory-dependent diagnosis of sepsis.Outcome measuresIdentification of any risk factors for neonatal sepsis.ResultsA total of 36 studies with 23 605 patients from secondary or tertiary level of care facilities in 10 countries were included. Six studies were rated as good quality, 8 as fair and 22 as poor. Four studies were omitted in the meta-analysis due to insufficient data. The significant risk factors were resuscitation (OR 2.70, 95% CI 1.36 to 5.35), low birth weight <1.5 kg (OR 3.37, 95% CI 1.59 to 7.13) and 1.5–2.5 kg (OR 1.36, 95% CI 1.01 to 1.83), low Apgar score at the first minute (OR 3.69, 95% CI 2.34 to 5.81) and fifth minute (OR 2.55, 95% CI 1.46 to 4.45), prematurity <37 weeks (OR 1.91, 95% CI 1.27 to 2.86), no crying at birth (OR 3.49, 95% CI 1.42 to 8.55), male sex (OR 1.30, 95% CI 1.01 to 1.67), prolonged labour (OR 1.57, 95% CI 1.08 to 2.27), premature rupture of membranes (OR 2.15, 95% CI 1.34 to 3.47), multiple digital vaginal examinations (OR 2.22, 95% CI 1.27 to 3.89), meconium-stained amniotic fluid (OR 2.72, 95% CI 1.58 to 4.69), intrapartum maternal fever (OR 2.28, 95% CI 1.18 to 4.39), foul-smelling vaginal discharge (OR 3.31, 95% CI 2.16 to 5.09) and low socioeconomic status (OR 1.93, 95% CI 1.11 to 3.35). We found considerable heterogeneity in the meta-analysis of 11 out of 15 identified risk factors.ConclusionMultiple risk factors for neonatal sepsis in Sub-Saharan Africa were identified. We revealed risk factors not listed by the WHO guidelines. The included studies overall had high risk of bias and high heterogeneity and thus, additional research of high quality is needed.PROSPERO registration numberCRD42020191067.

ObjectiveTo evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.DesignLongitudinal cohort study.SettingHospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.ParticipantsInfants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database.InterventionsGeneral movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6–8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database.Main outcome measuresMotor Optimality Scores Revised (MOS-R) at 3–5 months. Presence of developmental delay (DD) at 6–8 months.Results239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21–24, range 9–28) vs 25 (IQR 24–26, range 20–28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6–8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96).ConclusionsCompared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development.

ObjectiveTo determine the associations of WHO/UNICEF Joint Monitoring Program Water, Sanitation and Hygiene (WASH) Service Ladder service levels and sociodemographic factors with diarrhoeal disease among children under 5 years in Bishoftu town, Ethiopia.DesignA community-based cross-sectional study.SettingBishoftu town, Ethiopia, January–February 2022.ParticipantsA total of 1807 mothers with at least one child under 5 years were included. Sociodemographic and WASH variables were collected using a structured questionnaire. 378 drinking water samples were collected.OutcomeThe response variable was diarrhoeal disease among children under 5 years.ResultsThe 2-week prevalence of diarrhoeal disease among children under 5 years was 14.8%. Illiteracy (adjusted OR 3.15; 95% CI 1.54 to 6.47), occupation (0.35; 0.20 to 0.62), mother’s age (1.63; 1.15 to 2.31), family size (2.38; 1.68 to 3.39), wealth index (5.91; 3.01 to 11.59), residence type (1.98; 1.35 to 2.90), sex of the child (1.62; 1.17 to 2.24), child’s age (3.52; 2.51 to 4.93), breastfeeding status (2.83; 1.74 to 4.59), food storage practice (3.49; 1.74 to 8.26), unimproved drinking water source (8.16; 1.69 to 39.46), limited drinking water service (4.68; 1.47 to 14.95), open defecation practice (5.17; 1.95 to 13.70), unimproved sanitation service (2.74; 1.60 to 4.67), limited sanitation service (1.71; 1.10 to 2.65), no hygiene service (3.43; 1.91 to 6.16) and limited hygiene service (2.13; 1.17 to 3.86) were significantly associated with diarrhoeal disease.ConclusionIn this study, diarrhoea among children is a significant health issue. Child’s age, drinking water service, residence type and hygiene service were the largest contributors with respect to the prevalence of diarrhoeal disease. This investigation provides information that could help to inform interventions to reduce childhood diarrhoea. The findings suggest that state authorities should initiate robust WASH strategies to achieve the Sustainable Development Goal 3 agenda.