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Minority ethnic groups have been disproportionately affected by the COVID-19 pandemic. While the exact reasons for this remain unclear, they are likely due to a complex interplay of factors rather than a single cause. Reducing these inequalities requires a greater understanding of the causes. Research to date, however, has been hampered by a lack of theoretical understanding of the meaning of ‘ethnicity’ (or race) and the potential pathways leading to inequalities. In particular, quantitative analyses have often adjusted away the pathways through which inequalities actually arise (ie, mediators for the effect of interest), leading to the effects of social processes, and particularly structural racism, becoming hidden. In this paper, we describe a framework for understanding the pathways that have generated ethnic (and racial) inequalities in COVID-19. We suggest that differences in health outcomes due to the pandemic could arise through six pathways: (1) differential exposure to the virus; (2) differential vulnerability to infection/disease; (3) differential health consequences of the disease; (4) differential social consequences of the disease; (5) differential effectiveness of pandemic control measures and (6) differential adverse consequences of control measures. Current research provides only a partial understanding of some of these pathways. Future research and action will require a clearer understanding of the multiple dimensions of ethnicity and an appreciation of the complex interplay of social and biological pathways through which ethnic inequalities arise. Our framework highlights the gaps in the current evidence and pathways that need further investigation in research that aims to address these inequalities.

[...]the participating hospitals were either university hospitals (n = 9) or large teaching hospitals (n = 3), and 11 EDs had paediatric intensive care facilities. Collected data included age, sex, season, referral, comorbidity (chronic condition expected to last at least 1 year) [22], triage urgency, fever duration, fever measured at ED, presence of “red traffic light” symptoms for identifying risk of serious illness (alarming signs) (from the National Institute for Health and Care Excellence [NICE] guideline on fever [23]: decreased consciousness, ill appearance, work of breathing, meningeal signs, focal neurology, non-blanching rash, dehydration, status epilepticus), previous antibiotic use, vital signs (heart rate, respiratory rate, oxygen saturation, temperature, capillary refill time), laboratory results (white blood cell count, C-reactive protein [CRP], urinalysis), imaging (chest X-ray and other imaging), microbiological investigations (cultures and respiratory viral tests), and disposition (intensive care unit admission, general ward admission or discharge). The focus of infection was categorised as upper respiratory tract (otitis media, tonsillitis/pharyngitis, other), lower respiratory tract, gastrointestinal tract, urinary tract, skin, musculoskeletal, sepsis, central nervous system, flu-like illness, childhood exanthem, inflammatory syndrome, undifferentiated fever, or other. CRP, C-reactive protein; LRTI, lower respiratory tract infection; URTI, upper respiratory tract infection. *Patients could have identified viral co-infection. https://doi.org/10.1371/journal.pmed.1003208.g001 We aimed to improve data quality and standardised data collection by using a training module for the local clinical and research teams to optimise clinical assessment and data collection for febrile children.

Background Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability. Methods Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis. Results Patients most commonly presented clinically with sepsis without a source ( n  = 278, 35%), meningitis/encephalitis ( n  = 182, 23%), or pneumonia ( n  = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis ( n  = 131, 31%) and Streptococcus pneumoniae ( n  = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P  = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P  < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3–6.1, P  < 0.01; disability OR 3.4, 95% CI 1.8–6.4, P  < 0.001). Conclusions Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.

Background. The emergence of influenza A(H1N1) 2009 was met with increased reports of associated neurological manifestations. We aimed to describe neurological manifestations of influenza in adults and children in the United Kingdom that presented at this time. Methods. A 2-year surveillance study was undertaken through the British adult and pediatric neurological surveillance units from February 2011. Patients were included if they met clinical case definitions within 1 month of proven influenza infection. Results. Twenty-five cases were identified: 21 (84%) in children and 4 (16%) in adults. Six (29%) children had preexisting neurological disorders. Polymerase chain reaction of respiratory secretions identified influenza A in 21 (81%; 20 of which [95%] were H1N1) and influenza B in 4 (15%). Twelve children had encephalopathy (1 with movement disorder), 8 had encephalitis, and 1 had meningoencephalitis. Two adults had encephalopathy with movement disorder, 1 had encephalitis, and 1 had Guillain-Barré syndrome. Seven individuals (6 children) had specific acute encephalopathy syndromes (4 acute necrotizing encephalopathy, 1 acute infantile encephalopathy predominantly affecting the frontal lobes, 1 hemorrhagic shock and encephalopathy, 1 acute hemorrhagic leukoencephalopathy). Twenty (80%) required intensive care, 17 (68%) had poor outcome, and 4 (16%) died. Conclusions. This surveillance study described a cohort of adults and children with neurological manifestations of influenza. The majority were due to H1N1. More children than adults were identified; many children had specific encephalopathy syndromes with poor outcomes. None had been vaccinated, although 8 (32%) had indications for this. A modified classification system is proposed based on our data and the increasing spectrum of recognized acute encephalopathy syndromes.

Infection, particularly in the first 5 years of life, is a major cause of childhood deaths globally, many deaths from infections such as pneumonia and meningococcal disease are avoidable, if treated in time. Some factors that contribute to morbidity and mortality can be modified. These include organisational and environmental factors as well as those related to the child, family or professional. Examine what organizational and environmental factors and individual child, family and professional factors affect timing of admission to hospital for children with a serious infectious illness. Systematic review. Key search terms were identified and used to search CINAHL Plus, Medline, ASSIA, Web of Science, The Cochrane Library, Joanna Briggs Institute Database of Systematic Review. Primary research (e.g. quantitative, qualitative and mixed methods studies) and literature reviews (e.g., systematic, scoping and narrative) were included if participants included or were restricted to children under 5 years of age with serious infectious illnesses, included parents and/or first contact health care professionals in primary care, urgent and emergency care and where the research had been conducted in OECD high income countries. The Mixed Methods Appraisal Tool was used to review the methodological quality of the studies. Thirty-six papers were selected for full text review; 12 studies fitted the inclusion criteria. Factors influencing the timing of admission to hospital included the variability in children's illness trajectories and pathways to hospital, parental recognition of symptoms and clinicians non-recognition of illness severity, parental help-seeking behaviour and clinician responses, access to services, use and non-use of 'gut feeling' by clinicians, and sub-optimal management within primary, secondary and tertiary services. The pathways taken by children with a serious infectious illness to hospital are complex and influenced by a variety of potentially modifiable individual, organisational, environmental and contextual factors. Supportive, accessible, respectful services that provide continuity, clear communication, advice and safety-netting are important as is improved training for clinicians and a mandate to attend to 'gut feeling'. Relatively simple interventions such as improved communication have the potential to improve the quality of care and reduce morbidity and mortality in children with a serious infectious illness.

Background Paediatric early warning systems (PEWS) are a means of tracking physiological state and alerting healthcare professionals about signs of deterioration, triggering a clinical review and/or escalation of care of children. A proactive end-to-end deterioration solution (the DETECT surveillance system) with an embedded e-PEWS that included sepsis screening was introduced across a tertiary children's hospital. One component of the implementation programme was a sub-study to determine an understanding of the DETECT e-PEWS in terms of its clinical utility and its acceptability. Aim This study aimed to examine how parents and health professionals view and engage with the DETECT e-PEWS apps, with a particular focus on its clinical utility and its acceptability. Method A prospective, closed (tick box or sliding scale) and open (text based) question, e-survey of parents (n = 137) and health professionals (n = 151) with experience of DETECT e-PEWS. Data were collected between February 2020 and February 2021. Results Quantitative data were analysed using descriptive and inferential statistics and qualitative data with generic thematic analysis. Overall, both clinical utility and acceptability (across seven constructs) were high across both stakeholder groups although some challenges to utility (e.g., sensitivity of triggers within specific patient populations) and acceptability (e.g., burden related to having to carry extra technology) were identified. Conclusion Despite the multifaceted nature of the intervention and the complexity of implementation across a hospital, the system demonstrated clinical utility and acceptability across two key groups of stakeholders: parents and health professionals.

Little evidence exists about parental satisfaction and their influence on referral to paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT). This study aimed to examine the experiences of parents, children and clinicians of OPAT at a large tertiary children's hospital. A prospective e-survey, using closed and open questions, of parents (n = 33) of 33 children who had received OPAT (3 children completed a survey), and clinicians (n = 31) involved in OPAT at a tertiary hospital. Data were collected September 2016 to July 2018. Data were analysed using simple descriptive statistics. The results show that OPAT offered benefits (less stress, re-establishment of family life) compared to hospital-based treatment for parents and children, although some were anxious. Clinicians' referral judgements were based on child, home, and clinical factors. Some clinicians found the process of referral complex. Most parents and children were satisfied with the OPAT service and preferred the option of home-based treatment as it promoted the child's comfort and recovery and supported family routines.

Background Electronic early warning systems have been used in adults for many years to prevent critical deterioration events (CDEs). However, implementation of similar technologies for monitoring children across the entire hospital poses additional challenges. While the concept of such technologies is promising, their cost-effectiveness is not established for use in children. In this study we investigate the potential for direct cost savings arising from the implementation of the DETECT surveillance system. Methods Data were collected at a tertiary children’s hospital in the United Kingdom. We rely on the comparison between patients in the baseline period (March 2018 to February 2019) and patients in the post-intervention period (March 2020 to July 2021). These provided a matched cohort of 19,562 hospital admissions for each group. From these admissions, 324 and 286 CDEs were observed in the baseline and post-intervention period, respectively. Hospital reported costs and Health Related Group (HRG) National Costs were used to estimate overall expenditure associated with CDEs for both groups of patients. Results Comparing post-intervention with baseline data we found a reduction in the total number of critical care days, driven by an overall reduction in the number of CDEs, however without statistical significance. Using hospital reported costs adjusted for the Covid-19 impact, we estimate a non-significant reduction of total expenditure from £16.0 million to £14.3 million (corresponding to £1.7 million of savings – 11%). Additionally, using HRG average costs, we estimated a non-significant reduction of total expenditure from £8.2 million to £ 7.2 million (corresponding to £1.1 million of savings – 13%). Discussion and conclusion Unplanned critical care admissions for children not only impose a substantial burden on patients and families but are also costly for hospitals. Interventions aimed at reducing emergency critical care admissions can be crucial to contribute to the reduction of these episodes’ costs. Even though cost reductions were identified in our sample, our results do not support the hypothesis that reducing CDEs using technology leads to a significant reduction on hospital costs. Trial registration Current Controlled Trials ISRCTN61279068, date of registration 07/06/2019, retrospectively registered.

Group A streptococcal (GAS) disease shows increasing incidence worldwide. We characterised children admitted with GAS infection to European hospitals and studied risk factors for severity and disability. This is a prospective, multicentre, cohort study (embedded in EUCLIDS and the Swiss Pediatric Sepsis Study) including 320 children, aged 1 month to 18 years, admitted with GAS infection to 41 hospitals in 6 European countries from 2012 to 2016. Demographic, clinical, microbiological and outcome data were collected. A total of 195 (61%) patients had sepsis. Two hundred thirty-six (74%) patients had GAS detected from a normally sterile site. The most common infection sites were the lower respiratory tract (LRTI) (22%), skin and soft tissue (SSTI) (23%) and bone and joint (19%). Compared to patients not admitted to PICU, patients admitted to PICU more commonly had LRTI (39 vs 8%), infection without a focus (22 vs 8%) and intracranial infection (9 vs 3%); less commonly had SSTI and bone and joint infections ( p  < 0.001); and were younger (median 40 (IQR 21–83) vs 56 (IQR 36–85) months, p  = 0.01). Six PICU patients (2%) died. Sequelae at discharge from hospital were largely limited to patients admitted to PICU (29 vs 3%, p  < 0.001; 12% overall) and included neurodisability, amputation, skin grafts, hearing loss and need for surgery. More patients were recruited in winter and spring ( p  < 0.001). Conclusion : In an era of observed marked reduction in vaccine-preventable infections, GAS infection requiring hospital admission is still associated with significant severe disease in younger children, and short- and long-term morbidity. Further advances are required in the prevention and early recognition of GAS disease. What is Known: • Despite temporal and geographical variability, there is an increase of incidence of infection with group A streptococci. However, data on the epidemiology of group A streptococcal infections in European children is limited. What is New: • In a large, prospective cohort of children with community-acquired bacterial infection requiring hospitalisation in Europe, GAS was the most frequent pathogen, with 12% disability at discharge, and 2% mortality in patients with GAS infection. • In children with GAS sepsis, IVIG was used in only 4.6% of patients and clindamycin in 29% of patients.

Acute kidney injury (AKI), a common complication in paediatric intensive care units (PICU), is associated with increased morbidity and mortality. In this single centre, prospective, observational cohort study, neutrophil gelatinase-associated lipocalin in urine (uNGAL) and plasma (pNGAL) and renal angina index (RAI), and combinations of these markers, were assessed for their ability to predict severe (stage 2 or 3) AKI in children and young people admitted to PICU. In PICU children and young people had initial and serial uNGAL and pNGAL measurements, RAI calculation on day 1, and collection of clinical data, including serum creatinine measurements. Primary outcomes were severe AKI and renal replacement therapy (RRT). Secondary outcomes were length of stay, hospital acquired infection and mortality. The area under the Receiver Operating Characteristic (ROC) curves and Youden index was used to determine biomarker performance and identify optimum cut-off values. Of 657 children recruited, 104 met criteria for severe AKI (15∙8%) and 47 (7∙2%) required RRT. Severe AKI was associated with increased length of stay, hospital acquired infection, and mortality. The area under the curve (AUC) for severe AKI prediction for Day 1 uNGAL, Day 1 pNGAL and RAI were 0.75 (95% Confidence Interval [CI] 0∙69, 0∙81), 0∙64 (95% CI 0∙56, 0∙72), and 0.73 (95% CI 0∙65, 0∙80) respectively. The optimal combination of measures was RAI and day 1 uNGAL, giving an AUC of 0∙80 for severe AKI prediction (95% CI 0∙71, 0∙88). In this heterogenous PICU cohort, urine or plasma NGAL in isolation had poorer prediction accuracy for severe AKI than in previously reported homogeneous populations. However, when combined together with RAI, they produced good prediction for severe AKI.