Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people.

Post Covid Syndrome (PCS) is a complex multi-system disorder with a spectrum of presentations. Severity ranges from mild to very severe with variable duration of illness and recovery. This paper discusses the difficulties defining and describing PCS. We review the current understanding of PCS, epidemiology, and predisposing factors. We consider potential mechanisms including viral persistence, clotting dysfunction and immunity. We review presentation and diagnosis and finally consider management strategies including addressing symptom burden, rehabilitation, and novel therapies.

Fifteen-minute consultation: Managing post-COVID-19 syndrome (long COVID) in children and young people.

Post-COVID-19 syndrome is a new condition that can have a major impact on the physical and mental well-being of children and young people, affecting their ability to access activities including education. Paediatricians and general practitioners need to be able to assess and manage patients with this condition; making the diagnosis, excluding serious pathology, managing comorbidities and accessing appropriate management are crucial. This 15 minute consultation presents an approach to history taking, examination, investigations, management principles and referrals.

Child and adolescent chronic fatigue syndrome/myalgic encephalomyelitis: where are we now?

PURPOSE OF REVIEW: The current review aims to determine the recent evidence regarding cause, impact, effective treatment and prognosis of children and young people (CYP) affected by chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) at a time when the National Institute for Clinical Excellence guidelines in the United Kingdom are being reviewed and more research is called for worldwide. RECENT FINDINGS: CFS/ME is a debilitating illness with no clear cause. This review describes the heterogeneous clinical picture and the effects on the young person and family. Comorbidities such as mood disorders and pain are discussed including evidence for treatment. The various aetiological hypotheses are discussed and the precipitating factors identified. The evidence base is limited regarding effective treatment for CYP with CFS/ME, particularly the severely affected group. A large trial of online cognitive behavioural therapy with teenagers is being explored in the United Kingdom. The Lightning Process has been shown to be effective when added to medical care. SUMMARY: Current evidence is hampered by different diagnostic criteria, the heterogeneous nature of the condition, and limited number of small studies. There is a clear need for more research and larger studies exploring the cause of and most effective treatment for CYP with CFS/ME.

Goal-based measurement in paediatric settings: implications for practice.

There is an observed link between physical illness and mental health difficulties and an increased likelihood of mental health difficulties in young people with chronic health conditions. The main outcome focus in paediatric settings is on physical health outcomes and functioning. In terms of functioning, the focus is on quality of life, measures of emotional well-being and perceptions of personal change, which are likely to be multifaceted and vary between patients. To complement standardised and diagnostically based measures, goal-based outcome measurement may be considered. The aim of this paper is to build on previous research, to provide a reflective commentary based on the authors' clinical and research experience in the use and interpretation of goal-based outcomes, to address what using goal-based measures for outcome purposes in these settings means practically. Examples are provided to demonstrate the importance of considering meaningful outcomes of importance to young people and how professionals may presume that physical 'recovery' is the goal of treatment, but what recovery means to that young person may be very nuanced. Further key considerations and suggested phrasing are given to introduce and work with young people's goals.

Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study.

OBJECTIVES: Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5-16 years over 13 months. SECONDARY OBJECTIVES: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis. DESIGN: Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5-16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term). PARTICIPANTS: Patients 5-16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland. OUTCOME MEASURES: Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests. RESULTS: 285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years. CONCLUSIONS: Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people.

Discharge outcome analysis of 1089 transgender young people referred to paediatric endocrine clinics in England 2008-2021.

INTRODUCTION: The destination of transgender and gender variant young people referred by the National Health Service (NHS) Gender Identity Development Service (GIDS) to, and discharged from the two English paediatric endocrine liaison clinics is not known. METHODS: 1151 young people referred after full assessment by the GIDS; 827 to University College London Hospital since 2008; 324 to Leeds Children's Hospital since 2013. Discharge categorisation was by agreed criteria. Eleven emigrated and 51 self-discharged. 1089 had known outcomes. RESULTS: 999/1089 (91.7%) continued identifying as gender variant. 867/999 (86.8%) were discharged to adult gender identity clinics (GICs). 166/867 (19.1%) of these were <16 years and 701/867 (80.9%) ≥16 years at initial endocrine referral. No sex differences were seen. 38/999 (3.8%) opted for non-NHS services.90/1089 ceased identifying as gender variant. In 32/1089 (2.9%), this was subsequent to their first clinic appointment.58/1089 (5.3%) stopped treatment either with the gonadotropin releasing hormone analogue (GnRHa) or gender-affirming hormones (GAH) and reverted to their birth gender: <16 years (20/217; 9.2%); ≥16 years (38/872; 4.4%).Subdividing further, 16/217 (7.4%) <16 years ceased GnRHa and 4/217 (1.8%) after GAH. Of those ≥16 years, 33/872 (3.8%) ceased GnRHa and 5/872 (0.6%) GAH. CONCLUSIONS: At discharge, 91.7% continued as transgender or gender variant, 86.8% sought ongoing care through NHS GICs. 2.9% ceased identifying as transgender after an initial consultation prior to any endocrine intervention and 5.3% stopped treatment either with GnRHa or GAH, a higher proportion in the <16 year compared with the ≥16 year groups.

How fair is our service? Evaluating access to specialist paediatric care.

OBJECTIVE: To assess equity of access to paediatric outpatient clinics in our hospital. DESIGN/SETTING: Retrospective analysis of consecutive accepted referrals to allergy, asthma, epilepsy, general paediatrics, rapid access, chronic fatigue syndrome, diabetes and endocrine outpatient clinics. PATIENTS: 32 369 new patients, April 2007 to June 2018. RESULTS: Among local patients (58.1%) 0.2%-2.5% of patients referred to each clinic lived in the least deprived quintile, and 43.5%-48.4% in the most deprived quintile-similar to inpatient admissions and the local population. Tertiary clinics showed a much higher proportion of patients from the least deprived quintiles (15.9%-26.2%). CONCLUSIONS: Local outpatient referrals broadly reflected the socioeconomic distribution, although not necessarily the distribution of need, of our local population. A relatively high proportion of patients in tertiary clinics were from more affluent postcodes, highlighting the need for referral inequalities to be evaluated across networks or regions.

Role of gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests in differentiating patients with hypogonadotropic hypogonadism from those with constitutional delay of growth and puberty.

BACKGROUND: Delayed puberty can be due to either constitutional delay of growth and puberty (CDGP) or hypogonadotropic hypogonadism (HH). Differentiating between the two using current testing can be difficult. We assessed the utility of a GnRH test in combination with a 3-d and 19-d human chorionic gonadotropin (HCG) test to discriminate between the two conditions. METHODS: We performed a retrospective analysis of 43 boys with pubertal delay who required pubertal induction with testosterone. All were followed through puberty; 29 were subsequently diagnosed with CDGP and 14 with HH. A standard GnRH test (2.5 microg/kg) was undertaken and was followed by a short [3 d; n = 38 (13 HH, 25 CDGP)] or extended [19 d; n = 31 (12 HH, 19 CDGP)] HCG stimulation test, or both [n = 27 (11 HH, 16 CDGP)]. Receiver operating characteristic analysis was performed to assess the performance of the tests. RESULTS: Peak testosterone concentrations to both 3-d and 19-d HCG tests were significantly lower in patients with HH compared with CDGP. The 19-d test performed better than the 3-d test, and a combination of the LHRH, 3-d and 19 d HCG test [peak LH cutoff, 2.8 U/liter; peak 3-d testosterone cutoff, 1.04 microg/liter (3.6 nmol/liter); peak 19-d testosterone cutoff, 2.75 microg/liter (9.5 nmol/liter)] gave a sensitivity and a specificity of 100%. CONCLUSIONS: Our data suggest that a GnRH test in combination with both a 3-d and 19-d HCG test may aid in differentiating between CDGP and HH.