BackgroundPneumonia, diarrhoea, and malaria are among the leading causes of death in children. These deaths are largely preventable if appropriate care is sought early. This review aimed to determine the percentage of caregivers in low- and middle-income countries (LMICs) with a child less than 5 years who were able to recognise illness in their child and subsequently sought care from different types of healthcare providers.Methods and FindingsWe conducted a systematic literature review of studies that reported recognition of, and/or care seeking for episodes of diarrhoea, pneumonia or malaria in LMICs. The review is registered with PROSPERO (registration number: CRD42011001654). Ninety-one studies met the inclusion criteria. Eighteen studies reported data on caregiver recognition of disease and seventy-seven studies on care seeking. The median sensitivity of recognition of diarrhoea, malaria and pneumonia was low (36.0%, 37.4%, and 45.8%, respectively). A median of 73.0% of caregivers sought care outside the home. Care seeking from community health workers (median: 5.4% for diarrhoea, 4.2% for pneumonia, and 1.3% for malaria) and the use of oral rehydration therapy (median: 34%) was low.ConclusionsGiven the importance of this topic to child survival programmes there are few published studies. Recognition of diarrhoea, malaria and pneumonia by caregivers is generally poor and represents a key factor to address in attempts to improve health care utilisation. In addition, considering that oral rehydration therapy has been widely recommended for over forty years, its use remains disappointingly low. Similarly, the reported levels of care seeking from community health workers in the included studies are low even though global action plans to address these illnesses promote community case management. Giving greater priority to research on care seeking could provide crucial evidence to inform child mortality programmes.

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Many paediatric clinical research studies, whether observational or interventional, have as an eventual aim the identification or quantification of causal relationships. One might ask: does screen time influence childhood obesity? Could overuse of paracetamol in infancy cause wheeze? How does breastfeeding affect later cognitive outcomes? In this review, we present causal Directed Acyclic Graphs (DAGs) to a paediatric audience. DAGs are a graphical tool which provide a way to visually represent and better understand the key concepts of exposure, outcome, causation, confounding, and bias. We use clinical examples, including those outlined above, framed in the language of DAGs, to demonstrate their potential applications. We show how DAGs can be most useful in identifying confounding and sources of bias, demonstrating inappropriate statistical adjustments for presumed biases, and understanding threats to validity in randomised controlled trials. We believe that a familiarity with DAGs, and the concepts underlying them, will be of benefit both to researchers planning studies, and practicing clinicians interpreting them.

ObjectivesTo determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020.DesignNational retrospective cohort study.SettingEmergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records.Participants273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years.Main outcome measuresRates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016–2019.ResultsThe rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016–2019.ConclusionsNational lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.

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Long INterspersed Element class 1 (LINE‐1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition‐competent LINE‐1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE‐1 repressors and when mutated cause the autoinflammatory disorder Aicardi‐Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE‐1 retrotransposition. It has therefore been suggested that increased LINE‐1 activity may be the cause of aberrant innate immune activation in AGS. Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE‐1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE‐1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE‐1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE‐1‐derived nucleic acids driving autoinflammation in AGS.

The non-pharmaceutical interventions implemented to slow the spread of SARS-CoV-2 have had consequences on the transmission of other respiratory viruses, most notably paediatric respiratory syncytial virus (RSV) and influenza. At the beginning of 2020, lockdown measures in the southern hemisphere led to a winter season with a marked reduction in both infections. Intermittent lockdowns in the northern hemisphere also appeared to interrupt transmission during winter 2020/21. However, a number of southern and northern hemisphere countries have now seen delayed RSV peaks. We examine the implications of these unpredictable disease dynamics for health service delivery in Europe, such as paediatric hospital and intensive care bed space planning, or palivizumab prophylaxis. We discuss the challenges for RSV vaccine trials and influenza immunisation campaigns, and highlight the considerable research opportunities that have arisen with the SARS-CoV-2 pandemic. We argue that the rapid advances in viral whole genome sequencing, phylogenetic analysis, and open data sharing during the pandemic are applicable to the ongoing surveillance of RSV and influenza. Lastly, we outline actions to prepare for forthcoming influenza seasons and for future implementation of RSV vaccines.

A mother's expressed breast milk (MEBM) is overall the best feed for her preterm baby during the neonatal period, and is associated with improved short-term and long-term outcomes. Neonatal services should commit the resources needed to optimise its use. The place of banked donor expressed breast milk (DEBM) is less clear, but it probably has a role in reducing the risk of necrotising enterocolitis and sepsis in preterm infants at particularly high risk. There is considerable variation in the composition of human milk and nutrient fortification is often needed to achieve intrauterine growth rates. Human milk can transmit potentially harmful micro-organisms, and pasteurisation, which denatures some of the bioactive factors, is the only known way of preventing this. This is carried out for DEBM but not MEBM in the UK. Future research on human milk should focus on (a) critical exposure periods, (b) understanding better its bioactive properties, (c) the role of DEBM and (d) nutritional quality assurance.