Effectiveness of high flow nasal Cannula (HFNC) therapy compared to standard oxygen therapy (SOT) and continuous positive airway pressure (CPAP) in bronchiolitis.

High Flow Nasal Cannula therapy (HFNC) is a form of respiratory support for bronchiolitis. Recent evidence confirms HFNC reduces the risk of treatment escalation by nearly half (45%) compared to standard oxygen therapy (SOT), although most patients (75%) with mild-moderate respiratory distress manage well on SOT. The majority of children (60%) failing SOT respond well to HFNC making rescue use of HFNC a more cost-effective approach compared to its first-line use. HFNC is compared toCPAP in the setting of moderate to severe bronchiolitis. Patients on HFNC have a slightly elevated risk of treatment failure especially in severe bronchiolitis, but this does not translate to a significant difference in patient or healthcare centred outcomes. HFNC has improved tolerance, a lower complication rate and is more easily available in peripheral hospitals. It is therefore the preferred first line option followed by rescue CPAP. HFNC is clinically effective and safe to use in bronchiolitis of all severities.

Prevalence, Associated Factors, and Outcomes of Severe Acute Kidney Injury in Pediatric Acute Liver Failure: Single-Center Retrospective Study, 2003-2017.

OBJECTIVES: Our aim was to determine the prevalence and explanatory factors associated with outcomes in children with acute liver failure (ALF) admitted to the PICU, who also develop severe acute kidney injury (AKI). DESIGN: Retrospective cohort, 2003 to 2017. SETTING: Sixteen-bed PICU in a university-affiliated tertiary care hospital. PATIENTS: Admissions to the PICU with ALF underwent data review of the first week and at least 90-day follow-up. Patients with stages 2-3 AKI using the British Association of pediatric Nephrology definitions, or receiving continuous renal replacement therapy (CRRT) for renal indications, were defined as severe AKI. We excluded ALF cases on CRRT for hepatic-only indications. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics, proportion with severe AKI, illness severity and interventions, and outcomes (i.e., transplant, survival with native liver, overall survival, duration of PICU stay, and mechanical ventilation).Ninety-four children with ALF admitted to the PICU were included. Over the first week, 29 had severe AKI, and another eight received CRRT for renal/mixed reno-hepatic indications; hence, the total severe AKI cohort was 37 of 94 (39.4%). In a multivariable logistic regression model, peak aspartate aminotransferase (AST) and requirement for inotropes on arrival were associated with severe AKI. Severe AKI was associated with longer PICU stay and duration of ventilation, and lower spontaneous survival with native liver. In another model, severe AKI was associated with greater odds of mortality (odds ratio 7.34 [95% CI, 1.90-28.28], p = 0.004). After 90 days, 3 of 17 survivors of severe AKI had serum creatinine greater than the upper limit of normal for age. CONCLUSIONS: Many children with ALF in the PICU develop severe AKI. Severe AKI is associated with the timecourse of PICU admission and outcome, including survival with native liver. Future work should look at ALF goal directed renoprotective strategies at the time of presentation.

Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement.

There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second-termed "mini-puberty"-in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications.

Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019.

OBJECTIVES: Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. DESIGN: Single-center, retrospective study, 2010-2019. SETTING: Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. PATIENTS: Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. CONCLUSIONS: Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.

Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis.

OBJECTIVE: Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism. DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713). RESULTS: After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high. CONCLUSIONS: This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.

Teaching in Paediatrics for UK Foundation Doctors: A Cross-Sectional Study.

Background Most doctors will care for children regularly during their careers in settings such as the emergency department, general practice, surgery, or, for a minority, during paediatric specialist training. As such, exposure to topics related to child health ought to be part of the broad curriculum of learning offered to UK Foundation Programme doctors. Objective This study aimed to quantify teaching in paediatrics that is accessed by Foundation doctors. Methods A cross-sectional electronic survey of foundation year one or two (F1/F2) doctors at the end of the 2020-2021 academic year. Ethical approval was granted by the Imperial College London (ICL) Education Ethics Review Process (EERP 2021-082). Results Two-hundred and five Foundation doctors completed the survey, from 16 of the 18 Foundation schools. Respondents attended a median of two hours (interquartile range (IQR) 0-10) of paediatric teaching during the past 12 months, including a median of one hour (IQR 0-2) of core teaching and a median of one hour (IQR 0-9) of non-core teaching. Those who had worked in a paediatric post in the past 12 months, or who were interested in Paediatrics as a career, attended more median hours of teaching. Conclusions Although many doctors will care for children routinely during their later careers, the number of teaching hours in paediatrics experienced by Foundation doctors is low. The UK Foundation Programme should incorporate more teaching in paediatrics to increase exposure to child health amongst newly graduated and as-yet unspecialised doctors.

Safety and efficacy of continuous renal replacement therapy for children less than 10 kg using standard adult machines.

Continuous Renal Replacement Therapy (CRRT) machines are used off-label in patients less than 20 kg. Infant and neonates-dedicated CRRT machines are making their way into current practice, but these machines are available only in select centres. This study assesses the safety and efficacy of CRRT using adult CRRT machines in children ≤ 10 kg and to determines the factors affecting the circuit life in these children. DESIGN: Retrospective cohort study of children ≤ 10 kg who received CRRT (January 2010-January 2018) at a PICU in a tertiary care centre in London, UK. Primary diagnosis, markers for illness severity, CRRT characteristics, length of PICU admission and survival to PICU discharge were collected. Descriptive analysis compared survivors and non-survivors. A subgroup analysis compared children ≤ 5 kg to children 5-10 kg. Fifty-one patients ≤ 10 kg received 10,328 h of CRRT, with median weight of 5 kg. 52.94% survived to hospital discharge. Median circuit life was 44 h (IQR 24-68). Bleeding episodes occurred with 6.7% of sessions and hypotension for 11.9%. Analysis of efficacy showed a reduction in fluid overload at 48 h (P = 0.0002) and serum creatinine at 24 and 48 h (P = 0.001). Blood priming was deemed to be safe as serum potassium decreased at 4 h (P = 0.005); there was no significant change in serum calcium. Survivors had a lower PIM2 score at PICU admission (P < 0.001) and had longer PICU length of stay (P < 0.001).    Conclusion: Pending neonatal and infant dedicated CRRT machines, CRRT can be safely and effectively applied to children weighing ≤ 10 kg using adult-sized CRRT machines. WHAT IS KNOWN: • Continuous Renal Replacement Therapy can be used for a variety of renal and non-renal indications to improve outcomes for children in the paediatric intensive care unit. These include, persistent oliguria, fluid overload, hyperkalaemia, metabolic acidosis, hyperlactatemia, hyperammonaemia, and hepatic encephalopathy. • Young children ≤ 10 kg are most often treated using standard adult machines, off-label. This potentially places them at risk of side effects due to high extracorporeal circuit volumes, relatively higher blood flows, and difficulty in achieving vascular access. WHAT IS NEW: • This study found that standard adult machines were effective in reducing fluid overload and creatinine in children ≤ 10 kg. This study also assessed safety of blood priming in this group and found no evidence of an acute fall in haemoglobin or calcium, and a fall in serum potassium by a median of 0.3 mmol/L. The frequency of bleeding episodes was 6.7%, and hypotension requiring vasopressors or fluid resuscitation occurred with 11.9% of treatment sessions. • These findings suggest that adult CRRT machines are sufficiently safe and efficacious for routine use in PICU for children ≤ 10 kg and suggest that further research is undertaken, regarding the routine rollout of dedicated machines.

Building referral mechanisms for neonatal care in humanitarian emergency settings: A systematic review.

AIM: During humanitarian emergencies, women and children are particularly vulnerable to health complications and neonatal mortality rates have been shown to rise. Additionally, health cluster partners face challenges in coordinating referrals, both between communities and camps to health facilities and across different levels of health facilities. The purpose of this review was to identify the primary referral needs of neonates during humanitarian emergencies, current gaps and barriers, and effective mechanisms for overcoming these barriers. METHODS: A systematic review was performed using four electronic databases (CINAHL, EMBASE, Medline, and Scopus) between June and August 2019 (PROSPERO registration number CRD42019127705). Title, abstract, and full text screening were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The target population was neonates born during humanitarian emergencies. Studies from high-income countries and prior to 1991 were excluded. The STROBE checklist was used to assess for risk of bias. RESULTS: A total of 11 articles were included in the analysis; these were mainly cross-sectional, field-based studies. The primary needs identified were referrals from homes to health facilities before and during labour, and inter-facility referrals after labour to more specialised services. Some of the main barriers included a lack of roads and infrastructure for transport, staff shortages-especially among more specialised services, and a lack of knowledge among patients for self-referral. Mechanisms for addressing these needs and gaps included providing training for community healthcare workers (CHWs) or traditional birth attendants to identify and address antenatal and post-natal complications; education programmes for pregnant women during the antenatal period; and establishing ambulance services in partnership with local Non-Governmental Organizations. CONCLUSION: This review benefited from a strong consensus among selected studies but was limited in the quality of data and types of data that were reported. Based on the above findings, the following recommendations were compiled: Focus on local capacity-building programmes to address programmes acutely. Recruit CHWs to raise awareness of neonatal complications among pregnant women. Upskill CHWs to provide timely, appropriate and quality care during humanitarian emergencies.

Association between caregiver and household alcohol use and child behavior problems in KwaZulu Natal, South Africa.

We explored the association between household alcohol use and behavior problems among South-African children, using data from the Asenze study, a population-based cohort of South African children and their caregivers. Household alcohol use and child behavior were assessed when children were 6-8 years old. To examine the association, we performed linear regressions. The sample included 1383 children with complete data under the care of 1251 adults. Children living in a household where self-reported caregiver alcohol use was scored as hazardous (4.6%) had higher levels of problem behavior (ß = 1.94, 95% CI 0.06-3.82). There were no statistically significant associations between reported hazardous alcohol use by another member of the household (14.5%) and child problem behavior. Hazardous household alcohol use was associated with child problem behavior and this effect appeared to be mainly driven by primary caregiver use.

Characterization of a Hepatitis Outbreak in Children, 2021 to 2022.

Importance: After a cluster of pediatric cases of hepatitis of unknown etiology were identified in Scotland in March 2022, the World Health Organization published an outbreak alert, and more than 1010 probable cases were reported. Some cases progressed to acute liver failure and required liver transplant. Although many patients had positive results for adenovirus on polymerase chain reaction testing from whole blood samples and/or reported recent COVID-19 infection (with or without seropositivity), the precise pathogenesis remains unclear despite the high potential morbidity of this condition. Objective: To summarize the currently available evidence regarding novel pediatric hepatitis of unknown etiology (or novel hepatitis), encompassing case numbers, testing, management, and outcomes. Evidence Review: A rapid review of the literature from April 1, 2021, to August 30, 2022, aimed to identify all available published case series and case-control studies of novel hepatitis. The search included PubMed and references and citations of short-listed studies. Findings: A total of 22 available case series and case-control studies describing 1643 cases were identified, with 120 children (7.3%) receiving liver transplants and 24 deaths (1.5%). Outcome reporting and testing for adenovirus and SARS-CoV-2 was incomplete. Assessment of disease severity and management was mixed and results regarding testing for adenovirus and SARS-CoV-2 were inconsistent for both serological testing and testing of explant or biopsy liver samples. More recent studies suggest a more plausible role for adenovirus and/or adeno-associated virus 2. Conclusions and Relevance: This systematic review without meta-analysis describes the challenge posed by hepatitis of unknown etiology in terms of investigation and management, with many cases progressing to acute liver failure. The lack of clarity regarding pathogenesis means that these children may be missing the potential for targeted therapies to improve outcomes and avert the need for transplant. Clinicians, immunologists, and epidemiologists must collaborate to investigate the pathogenesis of this novel hepatitis.

Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder.

BACKGROUNDHypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODSUsing psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTSMC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSIONThese data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATIONClinicalTrials.gov NCT04179734.FUNDINGThis is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (CS-2018-18-ST2-002 and RP-2014-05-001).

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Importance: Despite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown. Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD. Design, Setting, and Participants: This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021. Interventions: A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion. Main Outcomes and Measures: Blood oxygen level-dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli. Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects. Conclusions and Relevance: These findings lay the foundations for clinical applications for kisspeptin in women with HSDD. Trial Registration: ISRCTN trial registry identifier: ISRCTN17271094.

Advances in medical management of acute liver failure in children: promoting native liver survival.

Paediatric acute liver failure (PALF) is defined as a biochemical evidence of acute liver injury in a child with no previous history of chronic liver disease characterised by an international normalised ratio (INR) of 1·5 or more unresponsive to vitamin K with encephalopathy, or INR of 2·0 or more with or without encephalopathy. PALF can rapidly progress to multiorgan dysfunction or failure. Although the transplant era has substantially changed the outlook for these patients, transplantation itself is not without risks, including those associated with life-long immunosuppression. Consequently, there has been an increased focus on improving medical management to prioritise bridging of patients to native liver survival, which is possible due to improved understanding of the underlying pathophysiology of multiorgan involvement in PALF. In this Review, we discuss recent advances in the medical management of PALF with an aim of reducing the need for liver transplantation. The Review will focus on the non-specific immune-mediated inflammatory response, extracorporeal support devices, neuromonitoring and neuroprotection, and emerging cellular and novel future therapeutic options.

Diabetes self-management during the COVID-19 pandemic and its associations with COVID-19 anxiety syndrome, depression and health anxiety.

INTRODUCTION: The effects of the COVID-19 pandemic on mental health have been profound. Mental health and diabetes self-care are inter-related. We examined whether COVID-19 anxiety, depressive symptoms and health anxiety were associated with domains of diabetes self-management and investigated whether greater COVID-19 anxiety syndrome would independently contribute to suboptimal diabetes self-care. RESEARCH DESIGN AND METHODS: Surveys were sent to people attending diabetes clinics of three London hospitals. Participants completed the Diabetes Self-Management Questionnaire (DSMQ), the COVID-19 Anxiety Syndrome Scale (C-19 ASS), which measures perseveration and avoidant maladaptive coping behaviour, assessed with measures of co-existent depressive symptoms and anxiety, controlling for age, gender and social deprivation. Clinical data, including pre- and post-lockdown HbA1c measures, were obtained from hospital records for 369 respondents, a response rate of 12.8%. RESULTS: Depressive symptom scores were high. Both pre-existing health anxiety and depressive symptoms were independently linked to improvable measures of diabetes care, as was lower socio-economic rank. However, avoidant COVID-19 anxiety responses were independently associated with higher diabetes self-care scores. HbA1c levels improved modestly over the year of UK lockdown in this cohort. CONCLUSION: During the height of lockdown, avoidant coping behaviours characteristic of the COVID-19 anxiety syndrome may in fact work to improve diabetes self-care, at least in the short term. We recommend screening for depressive symptoms and being aware of the significant minority of people with COVID-19 anxiety syndrome who may now find it difficult to re-engage with face-to-face clinic opportunities.

Social and Educational Outcomes in Patients With Biliary Atresia: A Systematic Review.

OBJECTIVES: To systematically review the social outcomes of patients with biliary atresia (BA), including educational, employment and family outcomes. METHODS: We conducted a systematic review of Medline, EMBASE, Global Health, Maternity and Infant Care Database, supplemented by reference searching. National Heart, Lung and Blood Institute scoring was conducted for quality assessment. The PROSPERO registration ID was CRD42020178846. RESULTS: Fifty-one studies were included (41 cohort, 10 cross-sectional), including 4631 participants across 16 countries. Cohorts were BA post-liver transplant (LT) (18 studies), native liver survivors (NLS) (16 studies), mixed (13 studies) and four other cohorts. Outcomes covered; education (n = 35), employment (n = 16), family outcomes (n = 22), and social functioning (n = 22). BA patients had lower school functioning scores than controls, with no difference between NLS versus post-LT. Between 2% and 48% of children required additional educational support. Between 60% and 100% of adult patients with BA were employed. Pregnancies were described in 17 studies, with small samples, and some noted complications. Social functioning scores were similar to healthy controls in 8 of 11 comparisons. CONCLUSIONS: Despite BA being the primary indication for liver transplantation in childhood, social outcomes for children and adolescents are predominantly reported in non-controlled, single-centre survey-based studies. School functioning is lower compared to peer groups, with no evidence of a difference for those having a liver transplant. We recommend routine psychosocial assessment of these patients during follow-up, alongside multi-centre collaborations, to maximise the quality of evidence for future patients.

Therapeutic plasma exchange in children with acute liver failure (ALF): is it time for incorporation into the ALF armamentarium?

Paediatric acute liver failure (PALF) is a rare but devastating condition with high mortality. An exaggerated inflammatory response is now recognised as pivotal in the pathogenesis and prognosis of ALF, with cytokine spill from the liver to systemic circulation implicated in development of multi-organ failure associated with ALF. With advances in medical management, especially critical care, there is an increasing trend towards spontaneous liver regeneration, averting the need for emergency liver transplantation or providing stability to the patient awaiting a graft. Hence, research is ongoing for therapies, including extracorporeal liver support devices, that can bridge patients to transplant or spontaneous liver recovery. Considering the immune-related pathogenesis and inflammatory phenotype of ALF, plasma exchange serves as an ideal liver assist device as it performs both the excretory and synthetic functions of the liver and, in addition, works as an immunomodulatory therapy by suppressing the early innate immune response in ALF. After a recent randomised controlled trial in adults demonstrated a beneficial effect of high-volume plasma exchange on clinical outcomes, this therapy was incorporated in European Association for the Study of Liver (EASL) recommendations for managing adult patients with ALF, but no guidelines exist for PALF. In this review, we discuss rationale, timing, practicalities, and existing evidence regarding the use of plasma exchange as an immunomodulatory treatment in PALF. We discuss controversies in delivery of this therapy as an extracorporeal device, and practicalities of use of plasma exchange as a 'hybrid' therapy alongside other extracorporeal liver assist devices, before finally reviewing outstanding research questions for the future.

'Birthing a Better Future': A mixed-methods evaluation of an exhibition on the early years of life.

BACKGROUND: Our study aimed to evaluate to what extent Zero2 Expo's 'Birthing a Better Future', a co-created multimedia exhibition, was effective in raising awareness on the importance of the first 1001 days of life and explore what refinements would help to optimize the impact of future exhibitions. METHODS: We conducted a mixed-methods evaluation of the exhibition delivered in the John Radcliffe Hospital, Oxford. Through convenience sampling, 14 participants were selected to participate in 12 structured interviews and 19 participants completed a questionnaire. Interviews were thematically analysed alongside quantitative analysis of questionnaire responses through Likert scales. RESULTS: The majority (78.6%, n = 11/14) of participants who completed the questionnaire either agreed or strongly agreed that the exhibition raised their awareness about the first 1001 days of life. This was supported by the analysis of interviews. The use of art was found to provoke an emotional engagement from participants. Participants felt that the length of the written pieces and location of the exhibition were important factors for designers to consider in future exhibitions. CONCLUSION: This study demonstrated that multimedia exhibitions, combining science with art, may be an effective way to raise awareness of public health messages. Engaging with key stakeholders will be an essential step in order to improve future public health exhibitions. PUBLIC CONTRIBUTION: When designing the study, the public reviewed the study tools, which were refined based on their feedback. At every phase of the study, members of the public who are artists co-created the exhibition content.

Adult Liver Disease Prognostic Modelling for Long-term Outcomes in Biliary Atresia: An Observational Cohort Study.

OBJECTIVES: To assess the utility of prognostic scoring systems for adolescents with biliary atresia (BA) surviving with native liver, for predicting the subsequent requirement for liver transplantation (LT). METHODS: Single-centre retrospective analysis of 397 BA patients who received Kasai Portoenterostomy (KP) 1980-1996 and survived with the native liver at 16 years. Laboratory and clinical variables at 16 years (timepoint 16 years) were used to calculate (i) LT allocation scores; Model for End-Stage Liver Disease [MELD/MELD-sodium (Na)], and UK End-Stage Liver Disease (UKELD); (ii) Mayo Primary Sclerosing Cholangitis risk score (MayoPSC) and (iii) a modified Paediatric End-Stage Liver Disease (PELD) score. Scores were compared between patients requiring LT after 16 years of age (LT > 16 years), and those who survived with native liver, at the latest follow-up. Additional subgroup analysis for patients with data available at 12 years (timepoint 12 years). RESULTS: MELD (area under the receiver operating characteristic [AUROC] 0.847) and UKELD (AUROC: 0.815) at 16 years of age predict the need for LT > 16 years. No advantage for MELD-Na over MELD was demonstrated. MELD >8.5 and UKELD >47 predicted LT > 16 years with 84% and 79% sensitivity and 73% and 73% specificity. PELD had a similar performance to MELD, but superiority to UKELD. MayoPSC revealed predictive accuracy for LT >16 years (AUROC 0.859), with a score of >0.87 predicting LT > 16 years with 85% sensitivity and 82% specificity. At timepoint 12 years, MELD and MayoPSC predicted LT >16 years. Change in MELD, PELD and MayoPSC between 12 and 16 years of age, was associated with LT >16 years. CONCLUSIONS: Adult LT allocation scores may help monitor progress in adolescent BA, but the omission of relevant risk factors limits their utility for listing in this cohort. A BA-specific prognostic score would improve the management of adolescent BA.