Two-year outcome of extracorporeal membrane oxygenation in COVID-19 related severe respiratory failure

Objectives: We sought to evaluate 2-year outcome of V-V ECMO support for COVID-19 related severe respiratory failure in our center. Method(s): Retrospective analysis of 41 consecutive patients (73% male, mean age 51.6+/-14.2 years, mean BMI 35.1+/-12.5 kg/m2) with critical hypoxemic and/or hypercapnic refractory respiratory failure (mean P/F ratio 67.9+/-14.3 mmHg, mean pCO2 77.6.0+/-185.7 mmHg, Murray Score 3.71+/-0.4) on V-V ECMO support from October 2020 to January 2022 Results: With mean support duration of 234.4+/-63.2 hours, 29 patients (70.7%) were successfully weaned off. Finally, 19 of them (46.3%) were discharged home with good neurological outcome (CPC 1,2). During followup, 30-day, 6-, 12-, and 24 -month survival rate was 61.3%, 46.2%, 41.9%, and 41,9% respectively. In survivor group shorter symptoms onset to respiratory failure time (4+/-4.7 vs. 7+/-6.7 days, p=0.04), higher P/F ration (86+/-41.5 vs. 65+/-37.5 mmHg, p=0.04) and norepinephrine support (0.03+/-0.06 vs. 0.09+/-0.12 ug/kg/min, p=0.04), and lower IL-6 level (12.3+/-7.5 vs. 25.9+/-8.8 ng/l, p=0.03) p=0.01) were analysed before cannulation. Mean in-ICU stay and in-hospital stay in survivors;groups reached 32.5+/-27.7 days and 42.6+/-35.8 days, respectively. All long-term survivors (17 patients) complained about slight functional health limitation only with normal 6MWT (542.6+/- 89.2 min), near to normal spirometry parameters (FEV/VC 87+/-7.4%, DLCO 63.1+/-13.7%, KCO 82.,1+/-19.4%) and minimal neurological disability (CPC 1-2) Conclusion(s): 2-year outcome of V-V ECMO support in COVID-19 severe respiratory failure is acceptable even in the scope of low-volume ECMO centre. Reported functional status of long-term survivors was good despite the complicated and prolonged in-hospital stay. (Table Presented).

Clinical features and acute management in children

Children account for a minority of cases of SARS-CoV-2 infection. The majority with acute infection are asymptomatic or have mild disease. Severe disease and mortality are reported in children with associated comorbidities such as complex neurodisability. Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS;also referred to as multisystem inflammatory syndrome in children (MIS-C)) is observed ~3-6 weeks after acute infection in an estimated 0.05% of cases. This is characterised by multiorgan involvement, and >50% of cases have myocardial dysfunction and require critical care admission for supportive care. Neurological, cardiac, gastrointestinal, renal and dermatological symptoms are all reported in acute and post-acute SARS-CoV-2 infection. To date, there is no evidence of a benefit from remdesivir, steroids or other investigative treatment in children during acute infection, and their use is recommended only on a case-by-case compassionate basis. Management of PIMS-TS is based on evidence from Kawasaki disease with immunomodulation and cardiac protection, and urgent RCT data are required. The collateral effects of the pandemic are likely to have long-term effects on children's physical and mental health.Copyright © ERS 2021.

Screening for psychosocial risk in caregivers of children with medical complexity during the COVID-19 pandemic: a cross-sectional study.

OBJECTIVE: The primary objective was to quantify psychosocial risk in family caregivers (FCs) of children with medical complexity (CMC) during the COVID-19 pandemic using the Psychosocial Assessment Tool (PAT). The secondary objectives were to compare this finding with the average PAT score of this population before the COVID-19 pandemic and to examine potential clinical predictors of psychosocial risk in FCs of CMC. DESIGN: Cross-sectional study. PARTICIPANTS: FCs of CMC were recruited from the Long-Term Ventilation Clinic at The Hospital for Sick Children, Toronto, Ontario, Canada. A total of 91 completed the demographic and PAT questionnaires online from 10 June 2021 through 13 December 2021. MAIN OUTCOME MEASURES: Mean PAT scores in FCs were categorised as 'Universal' low risk, 'Targeted' intermediate risk or 'Clinical' high risk. The effect of sociodemographic and clinical variables on overall PAT scores was assessed using multiple linear regression analysis. Comparisons with a previous study were made using Mann-Whitney tests and χ2 analysis. RESULTS: Mean (SD) PAT score was 1.34 (0.69). Thirty-one (34%) caregivers were classified as Universal, 43 (47%) as Targeted and 17 (19%) as Clinical. The mean PAT score (1.34) was significantly higher compared with the mean PAT score (1.17) found prior to the COVID-19 pandemic. Multiple linear regression analysis demonstrated an overall significant model, with the number of hospital admissions since the onset of COVID-19 being the only variable associated with the overall PAT score. CONCLUSION: FCs of CMC are experiencing significant psychosocial stress during the COVID-19 pandemic. Timely and effective interventions are warranted to ensure these individuals receive the appropriate support.

Learning Disability Awareness Week at Great Ormond Street Hospital

Background Learning Disability Week is an annual campaign from Mencap, dedicated to educating and raising awareness of learning disabilities. This year the theme of Learning Disability Week (20-26th June) was 'Living Life with a Learning Disability'. The campaign focuses on 'education and raising awareness about Learning Disabilities, ending discrimination and stigmas surrounding Learning Disabilities, and fighting and campaigning for equality and fair society' (Mencap). Aim The purpose of this presentation is to share examples and experiences of inclusive activities undertaken during LD Awareness week in a specialist children's hospital. Methods During the week the Learning Disability Team supported numerous guest visitors, activities and celebrations, and education sessions throughout the trust to promote awareness and engage positively with families and staff. Examples included music therapy, education, training on the use of specialist beds, and Dogs for Autism. The Learning Disability team collaborated with the Van Gogh Alive Exhibition on a spectacular display of sunflowers that brightened up the entrance of the hospital. We raised awareness by utilising Van Gogh's notable sunflower theme, as globally the sunflower is recognised as the symbol for hidden disabilities. During LD week the sunflower decals on the floor led the way to a stand in the main reception where the activities and information sharing took place. The Learning Disability team were supported during the week by Safeguarding, Play team, Neurodisability, Music Therapy, hospital school, Arts Team, communications team. Discussion Throughout the week the activities and education sessions were well attended and provided the team with a wonderful opportunity to engage with patients, families, and staff. The planning of the week took a considerate amount of time, including focus on health and safety, infection control and current COVID guidelines/social distancing measures. The support from members of multidisciplinary teams allowed for the planning and success of the week.

Using an objective computer task (QbTest) to aid the identification of attention deficit hyperactivity disorder (ADHD) in the Children and Young People Secure Estate (CYPSE): a feasibility randomised controlled trial.

OBJECTIVES: QbTest has been shown to improve time to decision/diagnosis for young people with attention deficit hyperactivity disorder (ADHD). The aim was to assess the feasibility of QbTest for young people in prison. DESIGN: Single-centre feasibility randomised controlled trial (RCT), with 1:1 allocation. Concealed random allocation using an online pseudorandom list with random permuted blocks of varying sizes. SETTING: One Young Offenders Institution in England. PARTICIPANTS: 355 young people aged 15-18 years displaying possible symptoms of ADHD were assessed for eligibility, 69 were eligible to take part and 60 were randomised. INTERVENTION: QbTest-a computer task measuring attention, activity and impulsivity. MAIN OUTCOME MEASURES: Eligibility, recruitment and retention rates and acceptability of randomisation and trial participation. RESULTS: Of the 355 young people assessed for eligibility, 69 were eligible and 60 were randomised (n=30 QbTest plus usual care; n=30 usual care alone). The study achieved the specified recruitment target. Trial participation and randomisation were deemed acceptable by the majority of participants. 78% of young people were followed up at 3 months, but only 32% at 6 months, although this was also affected by COVID-19 restrictions. Secondary outcomes were mixed. Participants including clinical staff were mostly supportive of the study and QbTest; however, some young people found QbTest hard and there were issues with implementation of the ADHD care pathway. There were no serious adverse events secondary to the study or intervention and no one was withdrawn from the study due to an adverse event. CONCLUSIONS: With adaptations, a fully powered RCT may be achievable to evaluate the effectiveness of QbTest in the assessment of ADHD in the Children and Young People Secure Estate, with time to decision (days) as the primary outcome measure. However, further programme developmental work is required to address some of the challenges highlighted prior to a larger trial. TRIAL REGISTRATION NUMBER: ISRCTN17402196.

Looking back, what have we learnt?

Introduction: Since the beginning of the COVID-19 pandemic, national and international registries of COVID-19 in patients with multiple sclerosis (MS) identified the most important risk factors for developing a severe form of COVID-19, mainly defined by oxygen-dependent pneumonia, and in the most severe cases the need for ventilation or death. Objective(s): to provide an overview of what we have learned about COVID-19 in patients with MS over the past 2 years Results: Although the majority of patients who died from COVID- 19 were patients with high neurological disability or other severe co-morbidities, anti-CD20 therapy was rapidly identified as a factor associated with worse prognosis of COVID-19, unlike other MS disease modifying therapies. A recent analysis of the COVISEP registry (2635 COVID-19 cases in patients with MS) with propensity scores found that this deleterious effect of anti-CD20 was predominant in the relapsing-remitting group only. This higher risk of severe COVID-19 associated with anti-CD20 therapy has led to prioritising patients on anti-CD20 for access to anti-COVID treatments, either pre-exposure or in case of infection. Anti-CD20 therapy has also been associated with a decreased humoral response after infection and an increased risk of postvaccination infection. With new Omicron variant subtypes and the advent of vaccination, the symptoms of COVID-19 and their severity have been largely modified, with severe forms becoming rarer. Conclusion(s): Overall, the therapeutic decision strategy for MS has been little changed in the era of COVID-19, given the major benefit of high efficacy therapies in relapsing remitting MS, but therapeutic choices in progressive patients must weigh the increased risk of severe COVID-19 in patients with higher disability against the modest therapeutic efficacy of approved or off-label treatments for progressive MS.

Impact of the COVID-19 pandemic on personal networks and neurological outcomes of people with multiple sclerosis: a case-control cross-sectional and longitudinal analysis

Introduction: Personal social networks impact the quality of life of people living with multiple sclerosis (pwMS). Objective / Aims: To evaluate the dynamic associations between personal network features and neurological function in pwMS and control participants during the COVID-19 pandemic and compare with the pre-pandemic period. Method(s): We first analyzed data collected from 8 cohorts of pwMS and control participants during the COVID-19 pandemic from March-December 2020. We then leveraged data collected between 2017-2019 in 3 of the 8 cohorts for longitudinal comparison. Participants completed a personal network questionnaire, which quantified the structure and composition of each person's personal network, including the health behaviors of network members. Neurological disability was quantified by three interrelated patient-reported outcomes: Patient Determined Disease Steps (PDDS), Multiple Sclerosis Rating Scale-Revised (MSRS-R), and Patient Reported Outcomes Measurement Information System (PROMIS)-Physical Function. We identified the network features associated with neurologic disability using paired t-tests and covariate-adjusted regressions. Result(s): In the cross-sectional analysis of the pandemic data from 1130 pwMS and 1250 control participants, percentage of network members perceived to have a negative health influence was associated with greater neurological symptom burden in pwMS (MSRS-R: Beta[95% CI]=2.181[1.082, 3.279], p<.001) and worse physical function in control participants (PROMIS-Physical Function: Beta[95% CI]=-5.707[-7.405, -4.010], p<.001). In the longitudinal analysis of 230 pwMS and 136 control participants, the percentage of people contacted weekly or less (p<.001) decreased during the COVID-19 pandemic for both pwMS (0.30+/-0.26 v. 0.19+/-0.22) and controls (0.23+/-0.25 v. 0.15+/-0.21) when compared to the pre-pandemic period. PwMS further experienced a greater reduction in network size (p<.001), increase in constraint (a measure of close ties of the network, p<.001) and decrease in maximum degree (highest number of ties of a network member, p<.001) than controls during the COVID-19 pandemic. These changes in network features were not associated with worsening neurological disability. Conclusion(s): Our findings suggest that negative health influences in personal networks are associated with worse disability in all participants and COVID-19 pandemic led to contraction of personal networks to a greater extent for pwMS than controls.

Parental experience of an early developmental surveillance programme for autism within Australian general practice: a qualitative study.

OBJECTIVES: Implementing support and services early in the life course has been shown to promote positive developmental outcomes for children at high likelihood of developmental conditions including autism. This study examined parents'/caregivers' experiences and perceptions about a digital developmental surveillance pathway for autism, the autism surveillance pathway (ASP), and usual care, the surveillance as usual (SaU) pathway, in the primary healthcare general practice setting. DESIGN: This qualitative study involves using a convenience selection process of the full sample of parents/caregivers that participated in the main programme, 'General Practice Surveillance for Autism', a cluster-randomised controlled trial study. All interviews were audio-recorded, transcribed and coded using NVivo V.12 software. An inductive thematic interpretive approach was adopted and data were analysed thematically. PARTICIPANTS: Twelve parents/caregivers of children with or without a developmental condition/autism (who participated in the main programme) in South Western Sydney and Melbourne were interviewed. SETTINGS: All interviews were completed over the phone. RESULTS: There were seven major themes and 20 subthemes that included positive experiences, such as pre-existing patient-doctor relationships and their perceptions on the importance of knowing and accessing early support/services. Barriers or challenges experienced while using the SaU pathway included long waiting periods, poor communication and lack of action plans, complexity associated with navigating the healthcare system and lack of understanding by general practitioners (GPs). Common suggestions for improvement included greater awareness/education for parents/carers and the availability of accessible resources on child development for parents/caregivers. CONCLUSION: The findings support the use of digital screening tools for developmental surveillance, including for autism, using opportunistic contacts in the general practice setting. TRIAL REGISTRATION NUMBER: ANZCTR (ACTRN12619001200178).

Exploring experiences with telehealth-delivered allied healthcare services for people with permanent and significant disabilities funded through a national insurance scheme: a qualitative study examining challenges and suggestions to improve services.

OBJECTIVES: In people with a disability, or their caregivers, who reported suboptimal experiences, the objectives were to explore: (1) challenges with telehealth-delivered allied health services during the COVID-19 pandemic and (2) suggestions to improve such services. DESIGN: Qualitative study based on an interpretivist paradigm and a phenomenological approach. SETTING: Participants who accessed allied healthcare via telehealth during the pandemic. PARTICIPANTS: Data saturation was achieved after 12 interviews. The sample comprised three people with permanent or significant disabilities, and nine carers/partners/family members of people with permanent or significant disabilities, who were funded by the Australian National Disability Insurance Scheme and had suboptimal experiences with telehealth. Semistructured one-on-one interviews explored experiences with telehealth and suggestions on how such services could be improved. An inductive thematic analysis was performed. RESULTS: Six themes relating to the first study objective (challenges with telehealth) were developed: (1) evoked behavioural issues in children; (2) reliant on caregiver facilitation; (3) inhibits clinician feedback; (4) difficulty building rapport and trust; (5) lack of access to resources and (6) children disengaged/distracted. Five themes relating to the second study objective (suggestions to improve telehealth services) were developed: (1) establish expectations; (2) increase exposure to telehealth; (3) assess suitability of specific services; (4) access to support workers and (5) prepare for telehealth sessions. CONCLUSIONS: Some people with permanent and significant disabilities who accessed allied healthcare via telehealth during the pandemic experienced challenges, particularly children. These unique barriers to telehealth need customised solutions so that people with disabilities are not left behind when telehealth services become more mainstream. Increasing experience with telehealth, setting expectations before consultations, supplying resources for therapy and assessing the suitability of clients for telehealth may help overcome some of the challenges experienced.

TREATMENT OF HYPERGLYCAEMIA IN ACUTE STROKE: RESULTS FROM THE TRIAL OF EXENATIDE IN ACUTE ISCHAEMIC STROKE (TEXAIS)

Background and aims: Hyperglycaemia in acute ischaemic stroke (AIS) is common, reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin therapies are difficult to implement and maintain, and may cause symptomatic hypoglycaemia. An alternative treatment is Exenatide, a GLP-1 agonist that lowers blood glucose with a very low risk of hypoglycaemia. Methods: The Trial of Exenatide in Acute Ischaemic Stroke (TEXAIS) enrolled adult patients with AIS ≤9 hours of stroke onset to receive treatment with short-acting Exenatide (5μg bid subcutaneous injection) or Standard care for 5 days, or until hospital discharge (whichever sooner).Primary outcome: proportion of patients with ≥8 point improvement in NIHSS score (or NIHSS 0-1) at 7 days. Results: 350 patients randomised, median age 71 years (IQR 62, 79), and median NIHSS 4 (IQR 2, 8). Planned recruitment (n=528) stopped early due to Covid and time constraints. On Admission the median blood glucose was 6.7 (IQR 5.70, 8.50), and 42% patients had hyperglycaemia (>7.0 mmol/L). Primary outcome occurred in 97/171 (56.7%) in Standard care group vs 104/170 (61.2%) in Exenatide group [aOR: 1.22 (CI 0.79, 1.88) p=0.38]. Mean daily per-patient frequency of hyperglycaemia was significantly less in the Exenatide group (p=0.002). No episodes of hypoglycaemia reported over the treatment period. Nausea/vomiting occurred in 7/174 (4.0%) patients on Exenatide. Conclusions: In this Phase 2 trial Exenatide did not significantly reduce neurological disability at 7 days. Exenatide significantly reduced frequency of hyperglycaemic events, and was safe to use. These results warrant further investigation with larger Phase 3 trials.

Hospital based social prescribing: Investigating parental views on the proposed Introduction of link workers for children with disabilities

Introduction: Children and young people (CYP) with a neurodisability often have complex needs which can significantly impact their quality of life. Unmet non-medical needs negatively correlate with well-being. COVID-19 has amplified the pressure on this population, catalysing our proposal for a new support service, based on the social prescribing link worker (LW) model supported by NHS England. Our innovative scheme will identify eligible CYP and their families within a hospital setting: with their agreement, a LW will help find and embed solutions to their unmet non-medical needs. The aim of this study was to gather the views of parents of CYP with neurodisability on the proposed service. Patients and methods: Forty UK-based parents of CYP with neurodisability completed an online survey (Qualtrix), distributed through social media. 11/40 were parents of young adults with disability. 28/40 of the CYP had cerebral palsy and/or autism. Results: COVID-19 had exacerbated circumstances for 90% of respondents. All except one were in favour of LW support;though only 7.5% previously knew what a LW was. Supporting their child towards independence;mental health;and social networks were priority areas. Reservations included not wanting input if their child was seriously ill;distinguishing between LW and social worker;worrying about whether the LW would have adequate specialist knowledge;and funding (postcode lottery). Conclusion: Respondents were strongly in favour of the proposed service. Based on their feedback, we will provide detailed information about the LW role, and recruit and support LW staff to provide a high quality, sustainable service.

Effects of maternal docosahexaenoic acid supplementation on brain development and neurodevelopmental outcomes of breastfed preterm neonates: protocol for a follow-up at preschool age of a randomised clinical trial (MOBYDIckPS)

IntroductionDocosahexaenoic acid (DHA), an omega-3 fatty acid, is important for brain development with possible implications in neurodevelopmental outcomes. In the two-arm, randomised, double-blind, placebo-controlled Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants trial, very preterm infants (<29 weeks’ gestation) were supplemented in high doses of DHA or placebo until they reached 36 weeks’ postmenstrual age. We propose a long-term neurodevelopmental follow-up of these children. This protocol details the follow-up at 5 years of age, which aims to (1) confirm our long-term recruitment capacity and (2) determine the spectrum of neurodevelopmental outcomes at preschool age following neonatal DHA supplementation.Methods and analysisThis long-term follow-up involves children (n=194) born to mothers (n=170) randomised to DHA (n=85) or placebo (n=85) from the five sites in Quebec when they will be 5 years’ corrected age. The primary outcome measure is related to the long-term recruitment capacity, which we determined as successful if 75% (±10%, 95% CI) of the eligible children consent to the 5-year follow-up study. Interviews with mothers will be conducted to assess various aspects of neurodevelopment at preschool age (executive functions, behavioural problems, global development and health-related quality of life), evaluated with standardised neurodevelopmental questionnaires. In addition, a semistructured interview conducted in a subset of the mothers will be used to determine their acceptability and identify barriers and enablers to their eventual participation to the next phase of the trial. This follow-up study will require approximately 22 months to be completed.Ethics and disseminationThis study was approved by the CHU de Québec-Université Laval Research Ethics Board (MP-20-2022-5926). Mothers will provide informed consent before participating in this study. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT02371460.

Neurodisability care in the time of COVID-19.

BACKGROUND: The COVID-19 pandemic resulted in an unprecedented societal and healthcare global crisis. Associated changes in regular healthcare provision and lifestyle through societal lockdown are likely to have affected clinical management and well-being of children/young people with neurodisability, who often require complex packages of multidisciplinary care. METHODS: We surveyed 108 families of children/young people with severe physical neurodisability and multiple comorbidities to understand how the pandemic had affected acute clinical status, routine healthcare provision, schooling and family mental and social well-being. RESULTS: A significant proportion of families reported missing hospital appointments and routine therapy, with subsequent worsening of symptoms and function. Families additionally described worsening stress and anxiety during the pandemic, regardless of their baseline level of socio-economic deprivation. CONCLUSION: This highlights the profound effect of the COVID-19 pandemic on health and function in young people with severe neurodisabilities and emphasizes the clear need to better understand how to support this vulnerable population moving forwards.

Indicators of high morbidity and poor functional outcome in acute ischemic stroke patients with concurrent covid-19

Objectives: Evidence suggests an association of increased cerebrovascular accidents frequency in patients diagnosed with the novel coronavirus disease, COVID-19. Coagulopathy resulting from the 2019 novel coronavirus (SARS-CoV-2) infection is suspected. This study aims at evaluating thrombotic markers in relation to stroke severity and functional outcomes in a patient cohort of acute ischemic stroke (AIS) with concurrent COVID-19. Methods: We performed a retrospective observational cohort study of 28 patients who tested positive for SARS-CoV-2 via polymerase chain reaction and concomitant AIS confirmed by brain imaging. We analyzed data regarding initial stroke presentation, markers of coagulopathy, and 90- day functional outcomes. Results: The patient cohort displayed high rate of comorbidities with 78.6% having at least 1 vascular risk factor. NIHSS had a median of 16 at initial presentation and median stroke volume of 52 mL. Median NIHSS at discharge or prior to death was 19, and median 90-day mRS was 4. Highest fibrinogen level recorded showed a median of 759.54 mg/dL (IQR 653.75-940.75), D-dimer and lactate dehydrogenase (LDH) showed a median highest recorded value 24,106 ng/mL (IQR 6105.00-80165.00) and 442 ng/mL (IQR 277.00-545.50), respectively. LDH (p=0.0008), D-dimer (p=0.001), and maximum fibrinogen levels (p=0.049) near the time of stroke significantly predicted final NIHSS and functional outcome 90-days after discharge. Conclusions: Adult patients with acute ischemic stroke and concurrent COVID-19 disease exhibited abnormally high markers of coagulopathy, and LDH, D-Dimer, and fibrinogen levels were predictors of morbidity and neurological disability at 90-days in this patient population. Further research is necessary to establish a definitive pattern and assess the ability to use these markers as prognostic elements of 90-day functional outcome.

Risk of COVID-19 in children treated for demyelinating disorders in the UK

Objective: Paediatric neurologists are concerned about the risk of COVID-19 in children with demyelinating disorders receiving immunomodulatory treatment. To investigate this, we collected data via the UK Childhood Neuro-Inflammatory Disorders (UK-CNID) network of the British Paediatric Neurology Association (BPNA). Methods: Survey of paediatric neurologists managing unvaccinated UK children (<18 years) with a demyelinating disorder (multiple sclerosis [MS];neuromyelitis optica spectrum disorder [NMOSD] and myelin oligodendrocyte glycoprotein antibody disease [MOGAD]) on immunomodulatory therapy with SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs between March and December 2020. Results: Of 151 UK children (MS 98, MOGAD 37, NMOSD 16) with a median age of 9 years (range 6-18y), with a demyelinating disorder, nine (6.0%) had a positive PCR for SARS-CoV-2. Five had MS and four MOGAD. Four were from south Asian or south-east Asian, four were White and one was mixed White and south Asian. Seven children had COVID-19 symptoms;two were asymptomatic. Two required a brief hospital admission for typical COVID-19 respiratory symptoms and the remaining five had mild symptoms including fever, rash, cough and headache. One with MOGAD, treated with azathioprine, developed transverse myelitis 12 days after COVID-19 onset. She recovered fully with a course of corticosteroids. MS patients were on following disease modifying therapies;dimethylfumarate (n=2), fingolimod (n=1);natalizumab (n=1) and ocrelizumab (n=1). MOGAD cases were on the following immune therapy: combination of oral prednisolone and intravenous immunoglobulin (n=2), prednisolone steroids (n=1) and azathioprine (n=1). Conclusions: In contrast to adult patients, who often have underlying co-morbidities and advanced neurological disabilities, we have identified that children treated for demyelinating disorders appear to have a milder COVID-19 course. Whilst the number of children treated for demyelinating disorders that developed COVID-19 is low, the overall mild course described may provide reassurance to neurologists, patients and family members.

Orphan disease: a Rare case of Malignant Osteopetrosis

Reports on clinical cases of orphan pathologies, as autosomal recessive type of infantile malignant osteopetrosis, have a great practical importance for scholars. Osteopetrosis may already manifest itself in utero. In early childhood, there is a classic triad of symptoms: increased bone density and fragility, severe anemia. Diagnostics and allogeneic hematopoietic stem cell transplantation at the age of up to 1 year can be cured and significantly increase life expectancy. Bone marrow transplantation is only treatment that has been proven to significantly alter course of autosomal recessive type of osteopetrosis. Inspide of successful transplantation may or-thopaedic, dental problems and their vision rarely significantly improves, however haemopoietic potential is restored and the long term prognosis is favourable. Herein we report a case of patient diagnosed with osteopetrosis and underwent allogeneic hematopoietic stem cell transplantation, with no prior determination type of mutation. Complexity of case: late diagnosis autosomal recessive type of osteopetrosis (at 3.1 years), despite characteristic early clinical manifestations, a protracted preparatory period associated with search for an unrelated donor and COVID-19 pandemic, for allogeneic-hematopoietic stem cell transplantation performed at the age of 4.3 years. In resulting, was engraftment of bone marrow transplant, with restoration hematopoietic func-tion, but with preserved neurological and physical disabilities in a form of psychomotor develop-ment retardation. Allogeneic hematopoietic stem cell transplantation led to restoration hematopoietic function of the graft in this case of late diagnosis osteopetrosis.

Cohort profile: early school years follow-up of the Asking Questions about Alcohol in Pregnancy Longitudinal Study in Melbourne, Australia (AQUA at 6).

PURPOSE: The Asking Questions about Alcohol in Pregnancy (AQUA) study, established in 2011, is a prebirth cohort of 1570 mother and child pairs designed to assess the effects of low to moderate prenatal alcohol exposure and sporadic binge drinking on long-term child development. Women attending general antenatal clinics in public hospitals in Melbourne, Australia, were recruited in their first trimester, followed up three times during pregnancy and at 12 and 24 months postpartum. The current follow-up of the 6-8-year-old children aims to strengthen our understanding of the relationship between these levels of prenatal alcohol exposure and neuropsychological functioning, facial dysmorphology, brain structure and function. PARTICIPANTS: Between June 2018 and April 2021, 802 of the 1342 eligible AQUA study families completed a parent-report questionnaire (60%). Restrictions associated with COVID-19 pandemic disrupted recruitment, but early school-age neuropsychological assessments were undertaken with 696 children (52%), and 482 (36%) craniofacial images were collected. A preplanned, exposure-representative subset of 146 children completed a brain MRI. An existing biobank was extended through collection of 427 (32%) child buccal swabs. FINDINGS TO DATE: Over half (59%) of mothers consumed some alcohol during pregnancy, with one in five reporting at least one binge-drinking episode prior to pregnancy recognition. Children's craniofacial shape was examined at 12 months of age, and low to moderate prenatal alcohol exposure was associated with subtle midface changes. At 2 years of age, formal developmental assessments showed no evidence that cognitive, language or motor outcome was associated with any of exposure level. FUTURE PLANS: We will investigate the relationship between prenatal alcohol exposure and specific aspects of neurodevelopment at 6-8 years, including craniofacial shape, brain structure and function. The contribution of genetics and epigenetics to individual variation in outcomes will be examined in conjunction with national and international collaborations.

Effectiveness and scalability of an electronic patient-reported outcome measure and decision support tool for family-centred and participation-focused early intervention: PROSPECT hybrid type 1 trial protocol.

INTRODUCTION: Early intervention (EI) endorses family-centred and participation-focused services, but there remain insufficient options for systematically enacting this service approach. The Young Children's Participation and Environment Measure electronic patient-reported outcome (YC-PEM e-PRO) is an evidence-based measure for caregivers that enables family-centred services in EI. The Parent-Reported Outcomes for Strengthening Partnership within the Early Intervention Care Team (PROSPECT) is a community-based pragmatic trial examining the effectiveness of implementing the YC-PEM e-PRO measure and decision support tool as an option for use within routine EI care, on service quality and child outcomes (aim 1). Following trial completion, we will characterise stakeholder perspectives of facilitators and barriers to its implementation across multiple EI programmes (aim 2). METHODS AND ANALYSIS: This study employs a hybrid type 1 effectiveness-implementation study design. For aim 1, we aim to enrol 223 caregivers of children with or at risk for developmental disabilities or delays aged 0-3 years old that have accessed EI services for three or more months from one EI programme in the Denver Metro catchment of Colorado. Participants will be invited to enrol for 12 months, beginning at the time of their child's annual evaluation of progress. Participants will be randomised using a cluster-randomised design at the EI service coordinator level. Both groups will complete baseline testing and follow-up assessment at 1, 6 and 12 months. A generalised linear mixed model will be fitted for each outcome of interest, with group, time and their interactions as primary fixed effects, and adjusting for child age and condition severity as secondary fixed effects. For aim 2, we will conduct focus groups with EI stakeholders (families in the intervention group, service coordinators and other service providers in the EI programme, and programme leadership) which will be analysed thematically to explain aim 1 results and identify supports and remaining barriers to its broader implementation in multiple EI programmes. ETHICS AND DISSEMINATION: This study has been approved by the institutional review boards at the University of Illinois at Chicago (2020-0555) and University of Colorado (20-2380). An active dissemination plan will ensure that findings have maximum reach for research and practice. TRIAL REGISTRATION NUMBER: NCT04562038.

Evaluating the impact of a common elements-based intervention to improve maternal psychological well-being and mother-infant interaction in rural Pakistan: study protocol for a randomised controlled trial.

INTRODUCTION: Millions of children in low resource settings are at high risk of poor development due to factors such as under nutrition, inadequate stimulation and maternal depression. Evidence-based interventions to address these risk factors exist, but often as a separate and overlapping package. The current study aims to evaluate the effectiveness of a common elements-based intervention to improve mother-infant interaction at 12 months post-partum. METHOD AND ANALYSIS: A two-arm, single-blinded, individual randomised controlled trial is being carried out in the community settings of the rural subdistrict of Gujar Khan in Rawalpindi, Pakistan. 250 pregnant women in third trimester with distress (Self-Reporting Questionnaire, cut-off score >9) have been randomised on 1:1 allocation ratio into intervention (n=125) and treatment-as-usual arms (n=125). The participants in the intervention arm will receive 15 individual sessions of intervention on a monthly basis by non-specialist facilitators. The intervention involves components of early stimulation, learning through play, responsive feeding, guided discovery using pictures, behavioural activation and problem solving. The primary outcome is caregiver-infant interaction at 12 months postpartum. The secondary outcomes include maternal psychological well-being, quality of life, social support and empowerment. Infant secondary outcomes include growth, nutrition and development. The data will be collected at baseline, 6 and 12 months postpartum. A qualitative process evaluation will be conducted to inform the feasibility of intervention delivery. ETHICS: Ethics approval for the present study was obtained from the Human Development Research Foundation Institutional Review Board, Islamabad Pakistan. DISSEMINATION: If proven effective, the study will contribute to scale-up care for maternal and child mental health in low resource settings, globally. The findings of the present study will be published in peer-reviewed journals and presented at conferences and community forums. TRIAL REGISTRATION NUMBER: NCT04252807.

CHILD-BRIGHT READYorNot Brain-Based Disabilities Trial: protocol of a randomised controlled trial (RCT) investigating the effectiveness of a patient-facing e-health intervention designed to enhance healthcare transition readiness in youth.

INTRODUCTION: Youth with brain-based disabilities (BBDs), as well as their parents/caregivers, often feel ill-prepared for the transfer from paediatric to adult healthcare services. To address this pressing issue, we developed the MyREADY TransitionTM BBD App, a patient-facing e-health intervention. The primary aim of this randomised controlled trial (RCT) was to determine whether the App will result in greater transition readiness compared with usual care for youth with BBD. Secondary aims included exploring the contextual experiences of youth using the App, as well as the interactive processes of youth, their parents/caregivers and healthcare providers around use of the intervention. METHODS AND ANALYSIS: We aimed to randomise 264 youth with BBD between 15 and 17 years of age, to receive existing services/usual care (control group) or to receive usual care along with the App (intervention group). Our recruitment strategy includes remote and virtual options in response to the current requirements for physical distancing due to the COVID-19 pandemic. We will use an embedded experimental model design which involves embedding a qualitative study within a RCT. The Transition Readiness Assessment Questionnaire will be administered as the primary outcome measure. Analysis of covariance will be used to compare change in the two groups on the primary outcome measure; analysis will be intention-to-treat. Interviews will be conducted with subsets of youth in the intervention group, as well as parents/caregivers and healthcare providers. ETHICS AND DISSEMINATION: The study has been approved by the research ethics board of each participating site in four different regions in Canada. We will leverage our patient and family partnerships to find novel dissemination strategies. Study findings will be shared with the academic and stakeholder community, including dissemination of teaching and training tools through patient associations, and patient and family advocacy groups. TRIAL REGISTRATION NUMBER: NCT03852550.