How to use podcasts in neurology.

Virtual learning resources such as podcasts and social media are increasingly used in medical education. Podcasts are one example of virtual learning, where prerecorded audio files are available to stream or download from the internet, usually without a fee and at any time. This gives listeners flexibility in when and where they engage with the educational material, enabling learning to be better tailored to individual needs. Podcasts are often enjoyed for their relaxed and conversational style. However, listeners must be aware of the lack of external peer review and incomplete coverage of information. There are also risks inherent to distant learning, including depersonalisation of medical education. We describe the roles that podcasts now play in neurological education, exploring some of the ways that they can be used to enhance neurological training both as a learner and educator and giving our top tips, based on our own experiences, for anyone keen to add to the expanding field of available podcasts.

European Training Requirements in Neonatology 2021: The ESPR, EAP, and UEMS Accredited European Syllabus for Neonatal Training.

INTRODUCTION: The European Union stipulates transnational recognition of professional qualifications for several sectoral professions, including medical doctors. The Union of European Medical Specialists (UEMS), in its "Charter on Training of Medical Specialists," defines the principles for high-level medical training. These principles are manifested in the framework for European Training Requirements (ETR), ensuring medical training reflects modern medical practice and current scientific findings. In 1998, the European Society for Paediatric Research developed the first ETR for Neonatology. We present the ETR Neonatology in its third iteration (ETR III), ratified by the European Academy of Paediatrics (EAP), and approved by UEMS in 2021. METHODS: In generating the ETR III, existing European policy documents on training requirements, including national syllabi and the European Standards of Care for Newborn Health were considered. To ensure the ETR III meets a pan-European standard of expertise in Neonatology, input from representatives from 27 European national paediatric/neonatal societies, and a European parent organisation, was sought. RESULTS: The ETR III summarises the requirements of contemporary training programs in Neonatology and offers a system for accrediting trainers and training centres. We describe the content of the ETR III training syllabus and means of gaining and assessing competency as a medical care provider in Neonatology. CONCLUSION: Graduates of courses following the ETR III Neonatology will obtain a certificate of satisfactory training completion which should be accepted by all European member states as a baseline qualification to practice as a specialist in neonatal medicine, enabling mutual recognition of status throughout Europe.

Development of musculoskeletal deficits in children with cystic fibrosis in later childhood.

Cystic fibrosis (CF) is a genetic condition primarily affecting the respiratory system, with the associated progressive lung damage and loss of function resulting in reduced lifespan. Bone health is also impaired in individuals with CF, leading to much higher fracture risk even in adolescence. However, the development of these deficits during growth and the relative contributions of puberty, body size and muscular loading remain somewhat unexplored. We therefore recruited 25 children with CF (10 girls, mean age 11.3 ± 2.9y) and 147 children without CF (75 girls, mean age 12.4 ± 2.6y). Bone characteristics were assessed using peripheral quantitative computed tomography (pQCT) at 4 % and 66 % distal-proximal tibia. Muscle cross-sectional area (CSA) and density (an indicator of muscle quality) were also assessed at the latter site. Tibial bone microstructure was assessed using high-resolution pQCT (HR-pQCT) at 8 % distal-proximal tibial length. In addition, peak jump power and hop force were measured using jumping mechanography. Group-by-age interactions and group differences in bone and muscle characteristics were examined using multiple linear regression, adjusted for age, sex and pubertal status and in additional models, height and muscle force. In initial models group-by-age interactions were evident for distal tibial total bone mineral content (BMC) and trabecular volumetric bone mineral density (vBMD), with a lower rate of age-related accrual evident in children with CF. In assessments of distal tibial microstructure, similar patterns were observed for trabecular number and thickness, and cortical CSA. In the tibial shaft, group-by-age interactions indicating slower growth in CF were evident for total BMC and cortical CSA, whilst age-independent deficits in CF were observed for several other variables. Peak jump power and hop force also exhibited similar interactions. Group-by-age interactions for bone were partially attenuated at the distal tibia and fully attenuated at the tibial shaft by adjustment for muscle force. These results suggest that bone and muscle deficits in children with CF develop throughout later childhood, independent of differences in pubertal stage and body size. These diverging growth patterns appear to be mediated by differences in muscle function, particularly for bone characteristics in the tibial shaft. Given the high fracture risk in this population from childhood onwards, development of interventions to improve bone health would be of substantial clinical value.

Use of ventilation/perfusion mismatch to guide individualised CPAP level selection in preterm infants: a feasibility trial.

OBJECTIVE: To measure within-subject changes in ventilation/perfusion (V'/Q') mismatch in response to a protocol of individualised nasal continuous positive airway pressure (CPAP) level selection. DESIGN: Single-arm, non-randomised, feasibility trial. SETTING: Three centres in the Children's Hospital of Philadelphia neonatal care network. PATIENTS: Twelve preterm infants of postmenstrual age 27-35 weeks, postnatal age >24 hours, and receiving a fraction of inspired oxygen (FiO2) >0.25 on CPAP of 4-7 cm H2O. INTERVENTIONS: We applied a protocol of stepwise CPAP level changes, with the overall direction and magnitude guided by individual responses in V'/Q' mismatch, as determined by the degree of right shift (kilopascals, kPa) in a non-invasive gas exchange model. Best CPAP level was defined as the final pressure level at which V'/Q' improved by more than 5%. MAIN OUTCOME MEASURES: Within-subject change in V'/Q' mismatch between baseline and best CPAP levels. RESULTS: There was a median (IQR) within-subject reduction in V'/Q' mismatch of 1.2 (0-3.2) kPa between baseline and best CPAP levels, p=0.02. Best CPAP was observed at a median (range) absolute level of 7 (5-8) cm H2O. CONCLUSIONS: Non-invasive measures of V'/Q' mismatch may be a useful approach for identifying individualised CPAP levels in preterm infants. The results of our feasibility study should be interpreted cautiously and replication in larger studies evaluating the impact of this approach on clinical outcomes is needed. TRIAL REGISTRATION NUMBER: NCT02983825.

Delivering an mRNA vaccine using a lymphatic drug delivery device improves humoral and cellular immunity against SARS-CoV-2.

The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic have captured the world's attention and remains an ongoing issue due to concerns of balancing protection against emerging variants of concern while also generating long-lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid encoding the spike protein in a lipid nanoparticle formulation (STI-7264) that generates robust humoral and cellular immunity following immunization of C57Bl6 mice. In an effort to improve immunity, a clinically focused lymphatic drug delivery device (MuVaxx) was engineered to modulate immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) and tested to measure adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine-producing CD8 T cells, neutralizing antibodies against the Washington (wild type) strain and South African (Beta) variants, and LN-resident spike-specific memory B cells. Remarkably, a 4-fold-elevated T cell response was observed in MuVaxx-administered vaccination compared to that of IM-administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatic-mediated delivery using MuVaxx for SARS-CoV-2 and VoC vaccines.

Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults.

OBJECTIVES: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. METHODS: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. RESULTS: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. CONCLUSIONS: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.

Update on the Coordinated Efforts of Looking After the Health Care Needs of Children and Young People Fleeing the Conflict Zone of Ukraine Presenting to European Emergency Departments-A Joint Statement of the European Society for Emergency Paediatrics and the European Academy of Paediatrics.

This joint statement by the European Society for Emergency Paediatrics and European Academy of Paediatrics aims to highlight recommendations for dealing with refugee children and young people fleeing the Ukrainian war when presenting to emergency departments (EDs) across Europe. Children and young people might present, sometimes unaccompanied, with either ongoing complex health needs or illnesses, mental health issues, and injuries related to the war itself and the flight from it. Obstacles to providing urgent and emergency care include lack of clinical guidelines, language barriers, and lack of insight in previous medical history. Children with complex health needs are at high risk for complications and their continued access to specialist healthcare should be prioritized in resettlements programs. Ukraine has one of the lowest vaccination coverages in the Europe, and outbreaks of cholera, measles, diphtheria, poliomyelitis, and COVID-19 should be anticipated. In Ukraine, rates of multidrug resistant tuberculosis are high, making screening for this important. Urgent and emergency care facilities should also prepare for dealing with children with war-related injuries and mental health issues. Ukrainian refugee children and young people should be included in local educational systems and social activities at the earliest opportunity.

Use of the SpO2/FiO2 Diagram to Assess Gas Exchange in Horses Under General Anaesthesia.

The aim of this study was to evaluate the validity of the SpO2/FiO2 diagram in estimating gas exchange in horses under general anaesthesia. In this prospective, controlled clinical study were included 10 horses under general anaesthesia. FiO2 was progressively reduced with the following steps: 0.6, 0.4, 0.3 and 0.21; SpO2 was recorded at each step. An arterial blood sample was collected at the steps of 1.0 and 0.21, to calculate intrapulmonary shunt with the Fshunt formula. The Fshunt value calculated at 0.21 FiO2 was defined as "Fshunt 0.21", the one calculated at 1.0 FiO2 as "Fshunt 1.0". The FiO2 vs SpO2 data points were analyzed using a computer algorithm which uses the haemoglobin and a fixed value for arterial-venous oxygen difference of 3.5 mL/dL. The algorithm estimates a shunt value fitting the obtained data with an ideal SpO2/FiO2 curve. The value of shunt (Sshunt) was considered for the study. Correlation between "Fshunt 1.0", "Fshunt0.21" and SShunt was determined using the Spearman Rank Correlation Coefficient test, the analysis of the regression curve and the coefficient of determination (r2). Values of P < .05 were considered statistically significant. A significant and strong correlation (P = .0069; r = 0.839; r2=0.6194) and a significant and moderate correlation (P = .0443; r = 0.644; r2=0.2336) was found between Sshunt and "Fshunt 1.0" and between Sshunt and "Fshunt 0.21", respectively. The SpO2/FiO2 diagram proved to be a useful and non-invasive tool to characterize gas exchange in horses under general anaesthesia and mechanical ventilation.

Spectrum, risk factors and outcomes of neurological and psychiatric complications of COVID-19: a UK-wide cross-sectional surveillance study.

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients <60 years. Relative to those >60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials.

Integrated care: a new model for dental education.

The COVID-19 pandemic has had a devastating health, economic and social impact on the UK health services. The learning from redeployment demonstrated that dental professionals can be rapidly integrated into the wider healthcare system, but the challenge is how this can be sustained in the future. This is an opportunity for dental training to be incorporated into a more integrated model of care, and this article outlines a collaboration between NHS England and NHS Improvement, Health Education England and Local Dental Networks to establish a novel training opportunity. This Assistant Dentist Integrated Care Pilot Programme has provided retention of dentists within areas of unmet need and introduced innovative opportunities for dental workforce transformation.

Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study.

BACKGROUND: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents. METHODS: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data. FINDINGS: Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9-5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1-17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group). INTERPRETATION: This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes. FUNDING: UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research.

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

Physical Activity in the Prevention of Childhood Obesity: The Position of the European Childhood Obesity Group and the European Academy of Pediatrics.

Obesity affects an increasing number of children and adolescents. Physical activity (PA) is a significant factor in the prevention of excessive body mass in the pediatric population. A significant percentage of pediatric population do not attain the public health recommendation for PA, and typically, those with higher levels of PA have lower content of body fat than less active peers. Although the development of childhood obesity is multifactorial, the decline in energy expenditure is considered as one of the most important determinants of excessive body weight. The lack of intervention causes that excess body weight to remain stable from birth through childhood and adolescence to adulthood. Accordingly, public health interventions are needed to increase the level of PA in the pediatric population. The task force from the European Childhood Obesity Group and the European Academy of Pediatrics reviewed English language meta-analyses, systematic reviews, randomized clinical trials, and observational studies from PubMed/MEDLINE, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases, from 2018 to August 2020, and developed a consensus statement. This statement presents the role of PA in the prevention of excessive body weight and gives age-appropriate recommendations for PA and recommendations for school-based interventions, parents, and guardians.

Pediatric Inflammatory Multisystem Syndrome: Statement by the Pediatric Section of the European Society for Emergency Medicine and European Academy of Pediatrics.

A rise in cases with a new hyperinflammatory disease in children has been reported in Europe and in the Unites States of America, named the Pediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2 (PIMS-TS). There appears to be a wide spectrum of signs and symptoms with varying degrees of severity, including a toxic shock like presentation with hypovolaemia and shock, and a Kawasaki-like presentation with involvement of the coronary arteries. Most of these children have evidence of a previous infection with SARS-CoV-2, or a history of significant exposure, but not all. Limited data exist on the incidence of PIMS-TS, but it remains a rare condition. Early recognition and escalation of care is important to prevent the development of serious sequelae, such as coronary artery aneurysms. Clinicians assessing febrile children in primary and secondary care should include PIMS-TS in their differential diagnoses. In children fulfilling the case definition, additional investigations should be undertaken to look for evidence of inflammation and multiorgan involvement. Suspected cases should be discussed with experts in pediatric infectious diseases at an early stage, and advice should be sought from critical care in more severe cases early. There is limited consensus on treatment; but most children have been treated with immunoglobulins or steroids, and with early consideration of biologicals such anti-TNF and anti-IL1 agents. Treatment should ideally be within the context of controlled treatment trials. Clinicians are encouraged to document and share their cases using research registries.

Off-label use of medicines in neonates, infants, children, and adolescents: a joint policy statement by the European Academy of Paediatrics and the European society for Developmental Perinatal and Pediatric Pharmacology.

Health-care professionals who prescribe medicines have the professional duty to choose medicines that are in the best interest of their individual patient, irrespective if that patient is an adult or a child. However, the availability of medicines with an appropriate label for pediatric use is lagging behind those for adults, and even available pediatric drugs are sometimes not suitable to administer to children. Consequently, health-care professionals often have no other option than to prescribe off-label medicines to children. An important reason for use of off-label medicines is to improve access to (innovative) treatments or to address medical needs and preferences of patients, especially when no other options are available. However, off-label use of medicines is in general not supported by the same level of evidence as medicines licensed for pediatric use. This may result in increased uncertainty on efficacy as well as the risk for toxicity and other side effects. In addition, liability may also be of concern, counterbalanced by professional guidelines.Conclusion: The purpose of this joint EAP/ESDPPP policy statement is to offer guidance for HCPs on when and how to prescribe off-label medicines to children and to provide recommendations for future European policy.

Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy.

Rationale: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a co-inhibitory checkpoint receptor that is expressed by naïve T-cells in lymph nodes (LNs) to inhibit activation against "self" antigens (Ags). In cancer, anti-CTLA-4 blocks inhibitory action, enabling robust activation of T-cells against tumor Ags presented in tumor draining LNs (TDLNs). However, anti-CTLA-4 is administered intravenously with limited exposure within TDLNs and immune related adverse events (irAEs) are associated with over-stimulation of the immune system. Methods: Herein, we first deliver anti-CTLA-4 in an orthotopic mammary carcinoma murine model using a nanotopographical microneedle-array device to compare its anti-tumor response to that from systemic administration. Additionally, to demonstrate the feasibility of lymphatic delivery in humans using the device, we use near-infrared fluorescence imaging to image delivery of ICG to LNs. Results: Our data show that lymphatic infusion results in more effective tumor growth inhibition, arrest of metastases, increased tumor infiltrating lymphocytes and complete responses when compared to conventional systemic administration. In clinical studies, we demonstrate for the first time that nanotopographic infusion can deliver ICG through the lymphatics directly to the axilla and inguinal LNs of healthy human volunteers. Conclusion: Taken together, these results suggest that regional delivery using a nanotopography-based microneedle array could revolutionize checkpoint blockade immunotherapy by reducing systemic drug exposure and maximizing drug delivery to TDLNs where tumor Ags present. Future work is needed to determine whether lymphatic delivery of anti-CTLA-4 can alleviate irAEs that occur with systemic dosing.

Update of the European paediatric respiratory medicine syllabus.

The 10-year-old European syllabus for paediatric respiratory medicine (PRM; also known as paediatric pulmonology) was updated by a consensus-based method using an expert task force for redrafting, and a subsequent Delphi process to achieve consensus. There was a high degree of consensus for the final syllabus, which has been streamlined and made more relevant to current practice. All modules are now mandatory apart from the undertaking of research projects, which is optional. Although there are still a number of countries in Europe which do not recognise PRM as a separate subspecialty, there are paediatric respiratory physicians practising in every country in Europe, and a current and harmonised European syllabus in the subspecialty remains important for defining the training and areas of practice of PRM practitioners.

Lyme disease: diagnosis and management.

Lyme disease (borreliosis) is a tick-borne bacterial infection caused by the spirochaete Borrelia burgdoferi, transmitted by hard-backed Ixodes ticks. Actual numbers of cases are increasing and it appears that the distribution across the UK is widening; however, it occurs most frequently in area of woodland, with temperate climate. It typically presents in mid to late summer. Lyme disease is a multisystem disease. The nervous system is the second most commonly affected system after the skin. Other systemic manifestations, such as carditis, keratitis, uveitis and inflammatory arthritis, rarely occur in European Lyme disease. In 2018, the National Institute for Health and Care Excellence has updated its guidelines on the diagnosis and management of Lyme disease. Here, we highlight important aspects of this guidance and provide a more detailed review of the clinical spectrum of neuroborreliosis, illustrated by cases we have seen.

Reversible cerebellar oedema secondary to profound hypomagnesaemia.

Magnesium is the second most abundant intracellular cation. Deficiency can cause several neurological complications, including cerebellar syndromes, with various MRI findings. These include cerebellar oedema, presumably through a similar mechanism to that in posterior reversible encephalopathy syndrome (PRES). People particularly vulnerable to deficiency include those with high alcohol consumption, excessive loss due to gastrointestinal pathology and those taking certain medications, including proton pump inhibitors. We report three patients with cerebellar syndromes associated with hypomagnesaemia. These cases support the previously reported association between hypomagnesaemia and reversible cerebellar dysfunction and illustrate the range of potential presentations. They highlight an uncommon but treatable cause of cerebellar ataxia that may present to acute neurological liaison services.