Incidence and Management of Inflammatory Arthritis in England before and during the Covid- 19 Pandemic: A Population-Level Cohort Study Using Opensafely

Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care;2) time to first rheumatology assessment;3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days;IQR 8-35 days) than before (21 days;9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic;however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic;however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinelycaptured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Extended Interval Dosing of Ocrelizumab Reduces Risk of Developing Hypogammaglobulinaemia

Introduction Disruption to clinical services, triggered by the COVID-19 pandemic, led to extended intervals between ocrelizumab treatments for some patients. Objectives To assess the rates of developing low immunoglobulin levels and timing of CD19+ B-cell count repopulation in a real-world clinical population. To assess for evidence of clinical or radiological MS disease activity with extended interval dosing of ocrelizumab. Methods We audited 712 patients given ocrelizumab by our seven clinical services. All monitoring of immunoglobulin levels and CD19+ cell counts were recorded. Disease activity was defined as on treatment clinical relapse, radiological activity, and EDSS progression. Results Low immunoglobulin levels developed in 102 patients, the odds ratio for developing hypogam- maglobulinaemia comparing extended to standard interval dosing was 0.42 (CI 0.22-0.81). Disease activity included 20 participants with clinical relapses and 72 with new MRI lesions. There was no evidence of excess clinical or radiological disease activity on switching to extended interval dosing. 38 had EDSS progression, giving an odds ratio comparing extended to standard interval dosing of 0.77 (CI 0.38-1.56). Conclusions This real-world data of extended interval dosing of ocrelizumab indicates lower rates of hypogammaglobulinaemia and no detrimental effect on short-term treatment efficacy.

Commentary on the American Society for Parenteral and Enteral Nutrition (ASPEN) position paper: Ethical aspects of artificially administered nutrition and hydration

"Ethics is knowing the difference between what you have a right to do and what is right to do.” -Potter Stewart. In their position paper, "Ethical Aspects of Artificially Administered Nutrition and Hydration: An ASPEN Position Paper”, [1] Schwartz et al. eloquently communicate key ethical concepts surrounding the care of patients receiving artificially administered nutrition and hydration (AANH). Ethically, all clinicians have the right and responsibility to provide nutrition-related access and resources to individuals in their care. At the same time, AANH is not always the right treatment to offer or provide. This revised position paper, published in Nutrition in Clinical Practice (NCP) in April 2021 [1], is the work of the American Society for Parenteral and Enteral Nutrition (ASPEN) International Clinical Ethics Position Paper Update Workgroup. It represents a comprehensive update of the Ethics Position Paper of the ASPEN Ethics Position Paper Task Force, published in NCP in 2010. [2] The revised position paper includes a detailed discussion of important ethical considerations not covered in the 2010 paper: cancer and AANH, eating disorders and AANH, ethical considerations raised during the COVID-19 pandemic, and an international perspective on ethics and AANH. The position paper also references the Cartagena Declaration of 2019, which "stresses the recognition that nutrition care is a human right” [1,3] and comments that "extrapolating from this document, it appears to support resource allocation in a fair, transparent and consistent fashion” [1,3]. This commentary summarizes the position paper and serves as a "call to action”. All medical professionals can and should engage in ethical aspects of AANH. Roles may vary depending on professional discipline and setting, but each interdisciplinary team member provides critical value. We also strongly encourage all readers to engage in conversations surrounding the topic of AANH and ethics: disseminating the principles in the position paper via local, regional, and national conference presentations, journal club discussions, grand rounds, and within the fundamental educational preparation of all clinicians involved in nutrition therapy practice. © 2022 The Author(s)

A Summary of COVID-19 Pandemic Assistance to US Forest Products Companies

Forest products and timber harvesting businesses were severely affected by the COVID-19 pandemic. This article describes how forest products companies used Paycheck Protection Program (PPP) loans to keep over 487,000 workers in the forest industry on payroll through the pandemic. This article also summarizes the Pandemic Assistance for Timber Harvesters and Haulers (PATHH) program, payments provided to timber harvesting and hauling businesses that experienced losses in revenue in 2020. Timber harvesting and hauling companies that received a PATHH payment reported US$1.27 trillion in total revenue lost between 2019 and 2020 because of the COVID-19 pandemic. © 2022 Forest Products Society. All rights reserved.

COVID-19 ADMISSIONS and MORTALITY in PATIENTS with EARLY INFLAMMATORY ARTHRITIS: RESULTS from A NATIONAL COHORT

Background: There has been a major concern about the impact of COVID-19 in patients with infammatory arthritis during the pandemic, with recommendations from governments for patients to shield. Objectives: Our aim was to describe the risk factors for COVID-19 hospitalisation and mortality amongst patients recruited to the National Early Infammatory Arthritis Audit (NEIAA) in England. Methods: An observational cohort study design was used. The population included adults in England with new diagnoses of infammatory arthritis between May 2018 and March 2021 who enrolled in NEIAA. The outcomes were hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition) and death due to COVID-19 (COVID-19 stated on a death certifcate), identifed via linkage with secondary care records. Hazard ratios were calculated using Cox proportional hazards models, with adjustment for patient factors (age, gender, smoking status, and comorbidity) and disease factors (seropositivity, 28-joint disease activity score, patient-reported disability (HAQ), and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from the date of diagnosis or February 2020 (whichever was later) and censored at a COVID-19 event, death or May 2021 (whichever was sooner). Results: 14,127 patients were included. The mean age was 57 years;62% were female;19% were current smokers, while 29% were ex-smokers. The frequency of comorbidities at baseline were: hypertension (19%), diabetes mellitus (9%), and lung disease (9%). Overall, 20% had two or more comorbidities. Rheumatoid factor or CCP antibodies were positive in 56%. At presentation, mean scores for DAS28 were 4.6 (+/-1.5), 1. 1 (+/-0.7) for HAQ, and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients: methotrexate was the most common (54%), followed by hydroxychloroquine (23%), and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 [95% CI: 0.79-1.10] and death: 0.31 [95% CI: 0.23-0.41]. Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 hospitalisation and death. Higher baseline DAS28 predicted COVID-19 hospitalisation (HR 1.24 [95% CI: 1.10-1.39]) and mortality (HR 1.33 [95% CI: 1.09-1.63]). Higher HAQ predicted both COVID-19 hospitalisation and death. Seropositivity was not a signifcant predictor of any COVID-19 event, nor was MSK-HQ. In unadjusted models, corticosteroids associated with COVID-19 death (HR 2.29 [95% CI: 1.02-5.13], and sulfasalazine monotherapy associated with COVID-19 hospitalisation (HR 1.93 [95% CI: 1.04-3.56]. In adjusted models, associations for corticoster-oids and sulfasalazine were no longer signifcant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion: The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic, with concerns about the use of csDMARDs and corticosteroids.1,2 Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic.

IMPACT of COVID-19 on the PRESCRIPTION of BIOLOGIC DMARDS: A POPULATION-LEVEL STUDY in ENGLAND

Background: There has been considerable uncertainty about the impact of biologic DMARDs (bDMARDs) on COVID-19 morbidity and vaccine efficacy, which may have influenced prescribing during the pandemic. Objectives: To assess trends in the prescription of three commonly used bDMARDs with different modes of action-adalimumab (ADA), rituximab (RTX) and tocilizumab (TOC)-in England before and during the COVID-19 pandemic. Methods: The National Health Service (NHS) Secondary Care Medicines dataset was utilised to analyse temporal trends in bDMARD prescriptions issued by all NHS hospital pharmacies in England. Monthly averages of prescriptions issued for ADA, RTX and TOC for combined indications, standardised using WHO Defned Daily Doses (DDD), were described from January 2019 to November 2021. Interrupted time-series analyses (ITSA) were used to estimate the effect of the pandemic on prescription trends for ADA, RTX and TOC;Newey-West standard errors with lags were used to account for autocorrelation between observation periods in these models. Results: Temporal trends in ADA, RTX and TOC prescriptions are shown in Figure 1. A 46% decrease in RTX prescriptions was observed between March and April 2020, from 1,338,300 DDD to 718,900 DDD, respectively, coinciding with the worsening COVID-19 pandemic in England. RTX prescriptions increased after May 2020, refected in the positive prescription trend observed in ITSA models (Table 1);however, RTX prescriptions remained below pre-pandemic levels, before decreasing again between November 2020 and February 2021. This coincided with increasing COVID-19 case numbers in England. For ADA, the pre-pandemic trend of increasing prescriptions continued during the pandemic, with no differences in prescription trends seen in ITSA models (Table 1). A 22% decrease in ADA prescriptions was observed between September and October 2020, from 2,037,800 DDD to 1,587,500 DDD, respectively, before rebounding to above pre-pandemic levels. Prescriptions for TOC increased during the pandemic, driven primarily by a 76% increase in prescriptions between December 2020 and January 2021, from 241,800 DDD to 425,000 DDD, respectively. Conclusion: Prescriptions for RTX in England halved during the early COVID-19 pandemic, and remain below pre-pandemic levels as of November 2021. This likely refects concerns about RTX use and increased COVID-19 mortality and reduced vaccine efficacy.1,2 In contrast, prescriptions for ADA have continued to increase during the pandemic, while prescriptions for TOC surged in December 2020, coinciding with the more widespread use of TOC for the treatment of severe COVID-19.

Impact of COVID-19 on outpatient appointments in children and young people in England: an observational study.

OBJECTIVES: To describe the impact of the COVID-19 pandemic on outpatient appointments for children and young people. SETTING: All National Health Service (public) hospitals in England. PARTICIPANTS: All people in England aged <25 years. OUTCOME MEASURES: Outpatient department attendance numbers, rates and modes (face to face vs telephone) by age group, sex and socioeconomic deprivation. RESULTS: Compared with the average for January 2017 to December 2019, there was a 3.8 million appointment shortfall (23.5%) for the under-25 population in England between March 2020 and February 2021, despite a total rise in phone appointments of 2.6 million during that time. This was true for each age group, sex and deprivation fifth, but there were smaller decreases in face to face and total appointments for babies under 1 year. For all ages combined, around one in six first and one in four follow-up appointments were by phone in the most recent period. The proportion of appointments attended was high, at over 95% for telephone and over 90% for face-to-face appointments for all ages. CONCLUSIONS: COVID-19 led to a dramatic fall in total outpatient appointments and a large rise in the proportion of those appointments conducted by telephone. The impact that this has had on patient outcomes is still unknown. The differential impact of COVID-19 on outpatient activity in different sociodemographic groups may also inform design of paediatric outpatient services in the post-COVID period.

Effectiveness and cost-effectiveness of universal school-based mindfulness training compared with normal school provision in reducing risk of mental health problems and promoting well-being in adolescence: the MYRIAD cluster randomised controlled trial.

BACKGROUND: Systematic reviews suggest school-based mindfulness training (SBMT) shows promise in promoting student mental health. OBJECTIVE: The My Resilience in Adolescence (MYRIAD) Trial evaluated the effectiveness and cost-effectiveness of SBMT compared with teaching-as-usual (TAU). METHODS: MYRIAD was a parallel group, cluster-randomised controlled trial. Eighty-five eligible schools consented and were randomised 1:1 to TAU (43 schools, 4232 students) or SBMT (42 schools, 4144 students), stratified by school size, quality, type, deprivation and region. Schools and students (mean (SD); age range=12.2 (0.6); 11-14 years) were broadly UK population-representative. Forty-three schools (n=3678 pupils; 86.9%) delivering SBMT, and 41 schools (n=3572; 86.2%) delivering TAU, provided primary end-point data. SBMT comprised 10 lessons of psychoeducation and mindfulness practices. TAU comprised standard social-emotional teaching. Participant-level risk for depression, social-emotional-behavioural functioning and well-being at 1 year follow-up were the co-primary outcomes. Secondary and economic outcomes were included. FINDINGS: Analysis of 84 schools (n=8376 participants) found no evidence that SBMT was superior to TAU at 1 year. Standardised mean differences (intervention minus control) were: 0.005 (95% CI -0.05 to 0.06) for risk for depression; 0.02 (-0.02 to 0.07) for social-emotional-behavioural functioning; and 0.02 (-0.03 to 0.07) for well-being. SBMT had a high probability of cost-effectiveness (83%) at a willingness-to-pay threshold of £20 000 per quality-adjusted life year. No intervention-related adverse events were observed. CONCLUSIONS: Findings do not support the superiority of SBMT over TAU in promoting mental health in adolescence. CLINICAL IMPLICATIONS: There is need to ask what works, for whom and how, as well as considering key contextual and implementation factors. TRIAL REGISTRATION: Current controlled trials ISRCTN86619085. This research was funded by the Wellcome Trust (WT104908/Z/14/Z and WT107496/Z/15/Z).

Impact of COVID-19 on primary care contacts with children and young people in England: longitudinal trends study 2015-2020.

BACKGROUND: The NHS response to COVID-19 altered provision and access to primary care. AIM: To examine the impact of COVID-19 on GP contacts with children and young people (CYP) in England. DESIGN AND SETTING: A longitudinal trends analysis was undertaken using electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum database. METHOD: All CYP aged <25 years registered with a GP in the CPRD Aurum database were included. The number of total, remote, and face-to-face contacts during the first UK lockdown (March to June 2020) were compared with the mean contacts for comparable weeks from 2015 to 2019. RESULTS: In total, 47 607 765 GP contacts with 4 307 120 CYP were included. GP contacts fell 41% during the first lockdown compared with previous years. Children aged 1-14 years had greater falls in total contacts (≥50%) compared with infants and those aged 15-24 years. Face-to-face contacts fell by 88%, with the greatest falls occurring among children aged 1-14 years (>90%). Remote contacts more than doubled, increasing most in infants (over 2.5-fold). Total contacts for respiratory illnesses fell by 74% whereas contacts for common non-transmissible conditions shifted largely to remote contacts, mitigating the total fall (31%). CONCLUSION: During the COVID-19 pandemic, CYP's contact with GPs fell, particularly for face-to-face assessments. This may be explained by a lower incidence of respiratory illnesses because of fewer social contacts and changing health-seeking behaviour. The large shift to remote contacts mitigated total falls in contacts for some age groups and for common non-transmissible conditions.

UTILISING VIRTUAL REALITY FOR REMOTE JOINT INJECTION TRAINING FOR THE POST-PANDEMIC RHEUMATOLOGIST

Background/Aims The impact of dealing with COVID-19 for rheumatology higher specialist trainees has been profound. Sacrifices were made to their training to support the UK's pandemic response. Virtual Reality (VR) has long been used as a solution for specific surgical skills;providing a hands-on experience to enable specific delivery of outcomes. We utilised existing technology alongside a specialist VR and haptics team to review ways at delivering a valid and reliable training tool to administer joint injections, beginning with the review of this procedure specific to the knee. We aimed to describe this process. Methods A qualitative study using focus groups was undertaken, one medical student, four higher specialty trainees and two consultants were convened in a focus group to review existing mannequin-based training with the purpose of identifying a skill to develop in virtual reality. A story board was developed through collaboration with a graphic designer. The scenario was imbedded into a virtual reality environment in collaboration with a virtual reality partner. Results The focus group identified intra-articular knee injection as the most appropriate rheumatology skill to develop. Storyboarding built a series of scenarios around clinical situations which would require injection or aspiration. Working with the engineering team we successfully mapped knee joint anatomy and rendered an authentic clinical environment for the storyboards to run inside. Conclusion Virtual reality training scenarios are complex to develop but have enormous potential to create immersive training and assessment experiences which are not boundaried by the challenges of social distancing and COVID-19 risks.

COVID-19 ADMISSIONS AND MORTALITY IN PATIENTS WITH EARLY INFLAMMATORY ARTHRITIS: RESULTS FROM A NATIONAL COHORT

Background/Aims Patients with inflammatory arthritis were identified as a potentially vulnerable group during the COVID-19 pandemic, with recommendations from the UK government to shield. We set out to describe the risks of COVID-19 according to initial treatment strategy amongst patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods NEIAA is an observational cohort design. It includes adults in England with a new diagnosis of inflammatory arthritis between May 2018 and March 2021. The outcomes of interest were death due to COVID-19 (COVID-19 stated on a death certificate) and hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition), identified using NHS Digital linkage. Cox proportional hazards models were used to calculate hazard ratios, with adjustment for patient factors (age, gender, smoking status, comorbidity) and disease factors (seropositivity, disease severity (DAS28), patient-reported disability (HAQ) and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from February 2020 or date of diagnosis (whichever was later) and censored at a COVID-19 event, May 2021 or death (whichever was sooner). Results 14,127 patients were included. Mean age was 57 (+/-16);62% were female. Smoking status: 19% current;29% ex-smokers. Comorbidities: 19% hypertension;9% diabetes;and 9% lung disease. Overall, 20% had two or more comorbidities. Rheumatoid Factor or CCP antibodies were positive in 56%. At presentation, mean scores were 4.6 (+/-1.5) for DAS28, 1.1 (+/-0.7) for HAQ and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients;methotrexate was most common (54%), then hydroxychloroquine (23%) and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 (95% CI: 0.79-1.10) and death: 0.31 (95% CI: 0.23-0.41). Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 events. Higher baseline DAS28 predicted COVID-19 admission (HR 1.24 (95% CI: 1.10-1.39)) and mortality (HR 1.33 (95% CI: 1.09-1.63)). Higher HAQ predicted both COVID-19 admission and death. Seropositivity was not a significant predictor of any COVID- 19 event, nor was MSK-HQ. Unadjusted, corticosteroids associated with COVID-19 death (HR 2.29 (95% CI: 1.02-5.13)), and sulfasalazine monotherapy associated with COVID-19 admission (HR 1.93 (95% CI: 1.04-3.56)). In adjusted models, associations for corticosteroids and sulfasalazine were no longer significant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic. Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic.

Bamlanivimab and Etesevimab Improve Symptoms and Associated Outcomes in Ambulatory Patients at Increased Risk for Severe Coronavirus Disease 2019: Results From the Placebo-Controlled Double-Blind Phase 3 BLAZE-1 Trial.

Background: In the phase 2/3 BLAZE-1 trial, bamlanivimab and etesevimab together reduced coronavirus disease 2019 (COVID-19)-related hospitalizations and any-cause mortality in ambulatory patients. Herein, we assess the impact of bamlanivimab and etesevimab treatment on the severity and length of symptoms and health outcomes among patients at increased risk for severe COVID-19. Methods: In the phase 3 portion of BLAZE-1 (NCT04427501), symptomatic patients with increased risk for severe COVID-19 were randomized (2:1) to a single infusion of 700 mg bamlanivimab and 1400 mg etesevimab or placebo. Hospitalization events, vital signs, and symptomatology were monitored throughout the trial. Results: Overall, 769 patients were randomized to bamlanivimab and etesevimab together (n = 511) or placebo (n = 258). The time to sustained symptom resolution was significantly shorter among patients who received bamlanivimab and etesevimab compared with placebo (8 vs 10 days; P < .01). The median time to first sustained symptom resolution of body aches and pain, chills, fatigue, feeling feverish, headache, and shortness of breath was significantly different in patients receiving bamlanivimab and etesevimab compared to placebo (P < .05). The proportion of patients who experienced COVID-19-related hospitalization by day 29 was significantly reduced among the bamlanivimab and etesevimab group compared with placebo (0.8% vs 5.4%; P < .01). The mean duration of hospital stay was numerically shorter among patients who received bamlanivimab and etesevimab (7.3 vs 13.5 days; P = .16), with fewer intensive care admissions. Conclusions: Patients receiving bamlanivimab and etesevimab together resolved their symptoms more rapidly than those receiving placebo. Bamlanivimab and etesevimab treatment was associated with reduced rates of hospitalizations and shorter hospital stays. Clinical Trials Registration: NCT04427501.

Which children and young people are at higher risk of severe disease and death after hospitalisation with SARS-CoV-2 infection in children and young people: A systematic review and individual patient meta-analysis.

BACKGROUND: We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people (CYP), within a systematic review and individual patient meta-analysis. METHODS: We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).PROSPERO: CRD42021235338. FINDINGS: 83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45-1.53) for 1 comorbidity; 2.58 (2.41-2.75) for 2 comorbidities; 2.97 (2.04-4.32) for ≥3 comorbidities. Corresponding odds ratios for death were: 2.15 (1.98-2.34) for 1 comorbidity; 4.63 (4.54-4.74) for 2 comorbidities and 4.98 (3.78-6.65) for ≥3 comorbidities. Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. IPD analysis demonstrated that, compared to children without co-morbidity, the risk difference of admission to critical care was increased in those with 1 comorbidity by 3.61% (1.87-5.36); 2 comorbidities by 9.26% (4.87-13.65); ≥3 comorbidities 10.83% (4.39-17.28), and for death: 1 comorbidity 1.50% (0.00-3.10); 2 comorbidities 4.40% (-0.10-8.80) and ≥3 co-morbidities 4.70 (0.50-8.90). INTERPRETATION: Hospitalised CYP at greatest vulnerability of severe disease or death with SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. FUNDING: RH is in receipt of a fellowship from Kidney Research UK (grant no. TF_010_20171124). JW is in receipt of a Medical Research Council Fellowship (Grant No. MR/R00160X/1). LF is in receipt of funding from Martin House Children's Hospice (there is no specific grant number for this). RV is in receipt of a grant from the National Institute of Health Research to support this work (grant no NIHR202322). Funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript.

Crossover symptoms of COVID-19 and influenza

Based on its quasi-predictable genetic markers, we urgently promoted vaccination, stocked up on Clinical Laboratory Improvement Amendments-waived test kits, and prescribed antiviral medications for patients and their families to protect our communities and reduce the potential for spread. When discussing COVID-19 infection with families, pediatricians will often include a caution for the infrequent possibility for multisystem inflammatory syndrome in children (MIS-C), but probably the most common and actionable concern is cardiac, especially for adolescent athletes. Since June 2020, there have also been several reported cases of MIS in adults3). Email them to llevine@mjhlifesciences.com О For references and additional resources, go to ContemporaryPediatrics.com/ crossover-symptoms-COVID-19influenza Russell Libby is founder and president of the Virginia Pediatric Group in Fairfax, Virginia;assistant clinical professor of pediatrics atthe University of Virginia and George Washington University schools of medicine;a board member of the Physicians Foundation;and a member of the Contemporary Pediatrics® Editorial Advisory Board.

Rationale and Design of the National Neuropsychology Network.

OBJECTIVE: The National Neuropsychology Network (NNN) is a multicenter clinical research initiative funded by the National Institute of Mental Health (NIMH; R01 MH118514) to facilitate neuropsychology's transition to contemporary psychometric assessment methods with resultant improvement in test validation and assessment efficiency. METHOD: The NNN includes four clinical research sites (Emory University; Medical College of Wisconsin; University of California, Los Angeles (UCLA); University of Florida) and Pearson Clinical Assessment. Pearson Q-interactive (Q-i) is used for data capture for Pearson published tests; web-based data capture tools programmed by UCLA, which serves as the Coordinating Center, are employed for remaining measures. RESULTS: NNN is acquiring item-level data from 500-10,000 patients across 47 widely used Neuropsychology (NP) tests and sharing these data via the NIMH Data Archive. Modern psychometric methods (e.g., item response theory) will specify the constructs measured by different tests and determine their positive/negative predictive power regarding diagnostic outcomes and relationships to other clinical, historical, and demographic factors. The Structured History Protocol for NP (SHiP-NP) helps standardize acquisition of relevant history and self-report data. CONCLUSIONS: NNN is a proof-of-principle collaboration: by addressing logistical challenges, NNN aims to engage other clinics to create a national and ultimately an international network. The mature NNN will provide mechanisms for data aggregation enabling shared analysis and collaborative research. NNN promises ultimately to enable robust diagnostic inferences about neuropsychological test patterns and to promote the validation of novel adaptive assessment strategies that will be more efficient, more precise, and more sensitive to clinical contexts and individual/cultural differences.

Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year.

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0-17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020-2021); hospitalizations due to all other non-traumatic causes in 2020-2021; hospitalizations due to all non-traumatic causes in 2019-2020; and hospitalizations due to influenza in 2019-2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15-17 year olds compared to 1-4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.

Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions (preprint)

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and calibration of an stochastic agent-based model Covasim to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. We used these estimates in Covasim (calibrated between September 01, 2020 and June 20, 2021), in June 2021, to explore whether planned relaxation of restrictions should proceed or be delayed. We found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination.