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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., Author(s): Emma C. Alexander [sup.1] , Akash Deep [sup.1] [sup.2] Author Affiliations: (1) grid.429705.d, 0000 0004 0489 4320, Paediatric Intensive Care Unit, King's College Hospital NHS Foundation Trust, , Denmark [...]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND. Hypoactive 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. METHODS. Using 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. RESULTS. MC4R 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. CONCLUSION. These 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 REGISTRATION. ClinicalTrials.gov NCT04179734. FUNDING. This 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)., Introduction Sexual arousal and desire are fundamental physiological processes in humans and are designed to drive sexual activity and ultimately reproduction at a population level. The presence of sexual arousal [...]

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. [ABSTRACT FROM AUTHOR]

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 (β = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the literature with the primary aim of identifying behavioural interventions to improve vitamin D stores in children from at-risk ethnic groups.Design: Review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PROSPERO registration number: CRD42017080932. Health Behaviour Model and Behaviour Change Wheel framework constructs used to underpin evaluation of interventions. Methodological quality evaluated using Cochrane Risk of Bias, Cochrane ROBINS-I and NHLBI tools.Setting: Databases Cochrane Library, MEDLINE, EMBASE, CINAHL with secondary search of Google Scholar. No country limits set. Papers between January 1990 and February 2018, published in English included. Anticipating study heterogeneity, outcome measures not pre-specified and identified from individual full papers. Updated literature search November 2020.Participants: Patient or population including pregnant women, newborns and children aged under 18 years, from Asian or African ethnic groups.Results: Of 10 690 articles screened, 298 underwent full-text review, with 24 ultimately included for data extraction. All identified studies conducted a vitamin D pharmacological supplementation intervention, with two also incorporating a behavioural intervention strategy. No study explicitly defined a primary aim of evaluating a behavioural intervention, undertaken to study its effect on vitamin D supplement uptake.Conclusions: There is a need to address the paucity of data in ethnic at-risk children on how behavioural interventions ideally developed and co-produced with the community under study, affect and help improve vitamin D uptake, within the antenatal and pregnancy phase as well as during childhood. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives To determine if increased exposure to clinical specialties at medical school is associated with increased interest in pursuing that specialty as a career after foundation training. Design A retrospective observational study. Setting 31 UK medical schools were asked how much time students spend in each of the clinical specialties. We excluded two schools that were solely Graduate Entry, and two schools were excluded for insufficient information. Main outcome measures Time spent on clinical placement from UK undergraduate medical schools, and the training destinations of graduates from each school. A general linear model was used to analyse the relationship between the number of weeks spent in a specialty at medical school and the percentage of graduates from that medical school entering each of the Core Training (CT1)/Specialty Training (ST1) specialties directly after Foundation Year 2 (FY2). Results Students spend a median of 85 weeks in clinical training. This includes a median of 28 weeks on medical firms, 15 weeks in surgical firms, and 8 weeks in general practice (GP). In general, the number of training posts available in a specialty was proportionate to the number of weeks spent in medical school, with some notable exceptions including GP. Importantly, we found that the number of weeks spent in a specialty at medical school did not predict the percentage of graduates of that school training in that specialty at CT1/ST1 level (ß coefficient=0.061, p=0.228). Conclusions This study found that there was no correlation between the percentage of FY2 doctors appointed directly to a CT1/ST1 specialty and the length of time that they would have spent in those specialties at medical school. This suggests that curriculum adjustments focusing solely on length of time spent in a specialty in medical school would be unlikely to solve recruitment gaps in individual specialties. [ABSTRACT FROM AUTHOR]

Abstract: Recent UK policy drivers such as the National Collaboration for Integrated Care and Support and Making Every Contact Count prioritise integrated care, an approach that seeks to provide more coordinated and seamless health and social care. In children's services, despite many partners, there are challenges around integrating care. A deprived borough of London ran short training and networking sessions for services supporting children and young people. This study examined whether intersectoral training would improve participants' knowledge of local services and joint working (including communication, navigation and confidence in collaboration). As part of a service evaluation, the study utilised a pre–post Likert scale survey design for each training session, a 1‐month follow‐up survey, and telephone interviews with a subsample of participants. The educational intervention was three sets of 1.5 hr educational workshops from December 2016 to February 2017. There were 302 attendances from 202 individuals from the health (n = 99), education (n = 145), social care (n = 39) and voluntary (n = 19) sectors. The pre and post surveys found significant increases in self‐assessed knowledge of health/education/social care/voluntary services and in some elements of joint working. However, these increases were not sustained in any domain after 1 month of follow‐up. There was also no difference in self‐assessments amongst those who attended three sessions compared to those who attended one or two. Telephone interviewees highlighted networking as being helpful and suggested that informative tasks and diverse attendance would be beneficial in future. To conclude, this study suggests that although short‐learning sessions may seem to improve immediate knowledge and some elements of joint working in the short term, any gains are not sustained in the long term. The cost effectiveness of such schemes is in doubt but may be improved by a more targeted delivery of content. [ABSTRACT FROM AUTHOR]

Objective: Suboptimal nutrition among children remains a problem among South Asian (SA) families. Appropriate complementary feeding (CF) practices can greatly reduce this risk. Thus, we undertook a systematic review of studies assessing CF (timing, dietary diversity, meal frequency and influencing factors) in children aged <2 years in Pakistan.Design: Searches between January 2000 and June 2016 in MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, CINAHL, Cochrane Library, BanglaJOL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research on CF practices in SA children aged 0-2 years and/or their families. Search terms: 'children', 'feeding' and 'Asians' with their derivatives. Two researchers undertook study selection, data extraction and quality appraisal (EPPI-Centre Weight of Evidence).Results: From 45 712 results, seventeen studies were included. Despite adopting the WHO Infant and Young Child Feeding guidelines, suboptimal CF was found in all studies. Nine of fifteen studies assessing timing recorded CF introduced between 6 and 9 months. Five of nine observed dietary diversity across four of seven food groups; and two of four, minimum meal frequency in over 50 % of participants. Influencing factors included lack of CF knowledge, low maternal education, socio-economic status and cultural beliefs.Conclusions: This is the first systematic review to evaluate CF practices in Pakistan. Campaigns to change health and nutrition behaviour are needed to meet the substantial unmet needs of these children. [ABSTRACT FROM AUTHOR]

Background: An estimated 2.6 million newborns died in 2016; over 98.5% of deaths occurred in low- and middle-income countries (LMICs). Neonates born preterm and small for gestational age are particularly at risk given the high incidence of infectious complications, cardiopulmonary, and neurodevelopmental disorders in this group. Quality improvement (QI) initiatives can reduce the burden of mortality and morbidity for hospitalised newborns in these settings. We undertook a systematic review to synthesise evidence from LMICs on QI approaches used, outcome measures employed to estimate effects, and the nature of implementation challenges.Methods: We searched Medline, EMBASE, WHO Global Health Library, Cochrane Library, WHO ICTRP, and ClinicalTrials.gov and scanned the references of identified studies and systematic reviews. Searches covered January 2000 until April 2017. Search terms were "quality improvement", "newborns", "hospitalised", and their derivatives. Studies were excluded if they took place in high-income countries, did not include QI interventions, or did not include small and sick hospitalised newborns. Cochrane Risk of Bias tools were used to quality appraise the studies.Results: From 8110 results, 28 studies were included, covering 23 LMICs and 65,642 participants. Most interventions were meso level (district and clinic level); fewer were micro (patient-provider level) or macro (above district level). In-service training was the most common intervention subtype; service organisation and distribution of referencing materials were also frequently identified. The most commonly assessed outcome was mortality, followed by length of admission, sepsis rates, and infection rates. Key barriers to implementation of quality improvement initiatives included overburdened staff and lack of sufficient equipment.Conclusions: The frequency of meso level, single centre, and educational interventions suggests that these interventions may be easier for programme planners to implement. The success of some interventions in reducing morbidity and mortality rates suggests that QI approaches have a high potential for benefit to newborns. Going forward, there are opportunities to strengthen the focus of QI initiatives and to develop improved, larger-scale, collaborative research into implementation of quality improvement initiatives for this high-risk group.Trial Registration: PROSPERO CRD42017055459 . [ABSTRACT FROM AUTHOR]

Sub-optimal nutrition among South Asian (SA) children living in high-income countries is a significant problem. High rates of obesity have been observed in this population, and differential complementary feeding practices (CFP) have been highlighted as a key influence. Our aim was to undertake a systematic review of studies assessing CFP in children under two years of age from SA communities living in high-income countries, including dietary diversity, timing, frequency and promotors/barriers. Searches covered January 1990–July 2018 using MEDLINE, EMBASE, Global Health, Web of Science, BanglaJOL, OVID Maternity and Infant Care, CINAHL, Cochrane Library, POPLINE and World Health Organisation (WHO) Global Health Library. Eligible studies were primary research on CFP in SA children aged 0–2 years. Search terms were "children", "feeding" and "South Asian", and derivatives. Quality appraisal used the Evidence for Policy and Practice Information (EPPI) Weight of Evidence scoring. From 50,713 studies, 13 were extracted with ten from the UK, and one each from the USA, Canada and Singapore. Sub-optimal CFP were found in all studies. All ten studies investigating timing reported complementary feeding (CF) being commenced before six months. Promoters/barriers influencing CFP included income, lack of knowledge, and incorrect advice. This is the first systematic review to evaluate CFP in SA children living in high-income countries and these findings should inform the development of effective interventions for SA infants in these settings. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alexander et al.)

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., Competing Interests: Declaration of interests AkD is Chair of Scientific Affairs of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) and Chair of the Working Group for Liver Failure in ESPNIC. AnD is a recipient of a National Institute for Health Research i4i grant to develop treatment for ALF with alginate microbead embedded hepatocytes and a Medical Research Council (MRC) grant for a first in human clinical trial of alginate embedded human hepatocytes as treatment for ALF (MRC MR/V038583/1); has been paid by Ambys and Johnson & Johnson for consultation; has a patent pending approval for alginate microbead manufacturing, and is part of the European Society for Paediatric Gastroenterology Hepatology and Nutrition. ALF guideline group. EF is in receipt of an MRC grant (MRC MR/V038583/1) for the research of hepatocyte transplantation; and has received payment for organising a Falk Symposium (unconnected). All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Sub-optimal nutrition among children remains a problem across South Asia (SA). Appropriate complementary feeding practices (CFP) can greatly reduce this risk. The primary objective of this systematic review (SR) of CF studies was to assess timing, dietary diversity, meal frequency and influencing factors in children under two in Bangladesh., Methods: Searches included English-language research published between January 2000 and June 2016 within MEDLINE, EMBASE, Global Health, Web of Science, OVID Maternity & Infant Care, BanglaJOL, Cochrane Library, CINAHL, POPLINE and WHO Global Health Library. Eligibility criteria: primary research concerning the adequacy of complementary feeding practices in South Asian children aged 0-2 years and/or their families. We excluded interventional papers and those focusing exclusively on breast-feeding. In total 45,712 titles and abstracts were screened against inclusion criteria, 860 of which received independent full text review by two reviewers. 36 papers relevant to Bangladesh were identified. The 'EPPI-Centre Weight of Evidence Framework' was used to objectively assess each study's value in answering the review question. As per WHO Infant and Young Children Feeding Guidelines (IYCF), introduction of CF was assessed as the proportion of infants aged 6-8 months who received solid, semi-solid or soft foods. Search terms were: "children", "feeding" and "Asians" with their derivatives. Two researchers undertook study selection, data extraction and quality appraisal., Results: Three cohort, 30 cross-sectional and 3 mixed methods studies were included. Despite adopting the WHO IYCF Guidelines, sub-optimal CF practices were found in many studies. Timely initiation of CF practices ranged from 24 to 83%. Achieved minimum dietary diversity ranged from 25% to 44% and minimum meal frequency from 33% to 81%. Influencing factors included maternal education, poor knowledge of CF practices and socioeconomic variables., Conclusions: This is the first systematic review to evaluate CF practices in Bangladesh. Despite adoption of the WHO IYCF guidelines, inadequate CFP remain in communities across Bangladesh., Trial Registration: PROSPERO Registration No: CRD42014014025., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2017.)