Management of a large outbreak of COVID-19 at a British Army training centre: lessons for the future.

INTRODUCTION: The COVID-19 pandemic has posed major challenges for infection control within training centres, both civilian and military. Here we present a narrative review of an outbreak that occurred at the Royal Military Academy Sandhurst (RMAS) in January-March 2021, in the context of the circulating, highly transmissible SARS-CoV-2 variant B.1.1.7. METHODS: Testing for SARS-CoV-2 was performed using a combination of reverse transcriptase PCR and Lateral Flow Devices (LFDs). Testing and isolation procedures were conducted in line with a pre-established symptom stratification system. Genomic sequencing was performed on 10 sample isolates. RESULTS: By the end of the outbreak, 185 cases (153 Officer Cadets, 32 permanent staff) had contracted confirmed COVID-19. This represented 15% of the total RMAS population. This resulted in 0 deaths and 0 hospitalisations, but due to necessary isolation procedures did represent an estimated 12 959 person-days of lost training. 9 of 10 (90%) of sequenced isolates had a reportable lineage. All of those reported were found to be the Alpha lineage B.1.1.7. CONCLUSIONS: We discuss the key lessons learnt from the after-action review by the Incident Management Team. These include the importance of multidisciplinary working, the utility of sync matrices to monitor outbreaks in real time, issues around Officer Cadets reporting symptoms, timing of high-risk training activities, infrastructure and use of LFDs. COVID-19 represents a vital learning opportunity to minimise the impact of potential future pandemics, which may produce considerably higher morbidity and mortality in military populations.

Changes in Depression and Anxiety Among Children and Adolescents From Before to During the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Importance: There is a growing body of high-quality cohort-based research that has examined changes in child and adolescent mental health during the COVID-19 pandemic vs before the pandemic. Some studies have found that child and adolescent depression and anxiety symptoms have increased, while others have found these symptoms to have remained stable or decreased. Objective: To synthesize the available longitudinal cohort-based research evidence to estimate the direction and magnitude of changes in depression and anxiety symptoms in children and adolescents assessed before and during the pandemic. Data Sources: Medline, Embase, and PsycInfo were searched for studies published between January 1, 2020, and May 17, 2022. Study Selection: Included studies reported on depression and/or anxiety symptoms, had cohort data comparing prepandemic to pandemic estimates, included a sample of children and/or adolescents younger than 19 years, and were published in English in a peer-reviewed journal. Data Extraction and Synthesis: In total, 53 longitudinal cohort studies from 12 countries with 87 study estimates representing 40 807 children and adolescents were included. Main Outcomes and Measures: Standardized mean changes (SMC) in depression and anxiety symptoms from before to during the pandemic. Results: The analysis included 40 807 children and adolescents represented in pre-COVID-19 studies and 33 682 represented in during-COVID-19 studies. There was good evidence of an increase in depression symptoms (SMC, 0.26; 95% CI, 0.19 to 0.33). Changes in depression symptoms were most conclusive for study estimates among female individuals (SMC, 0.32; 95% CI, 0.21 to 0.42), study estimates with mid to high income (SMC, 0.35; 95% CI, 0.07 to 0.63), and study estimates sourced from North America (SMC, 0.25; 95% CI, 0.15 to 0.36) and Europe (SMC, 0.35; 95% CI, 0.17 to 0.53). There was strong evidence that anxiety symptoms increased slightly during the pandemic (SMC, 0.10; 95% CI, 0.04 to 0.16), and there was some evidence of an increase in study estimates with mid to high income. Conclusions: This systematic review and meta-analysis of longitudinal studies including children and adolescents found an increase in depression symptoms during the COVID-19 pandemic, particularly among female individuals and those from relatively higher-income backgrounds.

The molecular dynamics of possible inhibitors for SARS-CoV-2.

The novel coronavirus SARS-CoV-2, responsible for the present COVID-19 global pandemic, is known to bind to the angiotensin converting enzyme-2 (ACE2) receptor in human cells. A possible treatment of COVID-19 could involve blocking ACE2 and/or disabling the spike protein on the virus. Here, molecular dynamics simulations were performed to test the binding affinities of nine candidate compounds. Of these, three drugs showed significant therapeutic potential that warrant further investigation: SN35563, a ketamine ester analogue, was found to bind strongly to the ACE2 receptor but weakly within the spike receptor-binding domain (RBD); in contrast, arbidol and hydroxychloroquine bound preferentially with the spike RBD rather than ACE2. A fourth drug, remdesivir, bound approximately equally to both the ACE2 and viral spike RBD, thus potentially increasing risk of viral infection by bringing the spike protein into closer proximity to the ACE2 receptor. We suggest more experimental investigations to test that SN35563-in combination with arbidol or hydroxychloroquine-might act synergistically to block viral cell entry by providing therapeutic blockade of the host ACE2 simultaneous with reduction of viral spike receptor-binding; and that this combination therapy would allow the use of smaller doses of each drug.Communicated by Ramaswamy H. Sarma.

Transitioning to digital first line intervention - validation of a brief online screener for early identification of a suspected eating disorder: study protocol.

BACKGROUND: Only one in four people with eating disorders seeks treatment, and of those who do seek treatment, 20% go on to experience a chronic course. Early intervention has been associated with better prognosis, with those seeking specialised intervention in the early stages of their illness more than twice as likely to achieve remission. Current screening measures typically require expert administration and are rarely validated across a spectrum of DSM-5 eating disorder presentations or for online use. In light of COVID-19 and increasing reliance on telehealth technologies in the intervention and delivery of mental health services, online assessments suitable for self-referral are likely to be the first step to seeking care. InsideOut Institute has developed a 6-item online screening tool for the purposes of identifying eating disorder risk and symptomatology, aimed specifically at increasing help-seeking behaviour in subsyndromal and early presentations. METHODS: This study investigates the reliability and validity of the InsideOut Institute Screener (IOI-S), using a cross-sectional survey research design. Participants aged 14 and over will complete an extensive baseline survey battery for evaluation. 50% of participants will be randomly selected for one follow-up re-test of the IOI-S only, 2 weeks post initial testing. The IOI-S will be analysed for statistical reliability on two parameters: internal consistency and test re-test reliability, and for statistical validity on four parameters: concurrent validity, sensitivity and specificity, convergent and discriminant validity. DISCUSSION: The rapid and ongoing shift to digital intervention has highlighted gaps and opportunities in our pathways to care. Adequate screening for eating disorders is a major gap. This study aims to validate an online screening tool for use in telehealth early intervention, designed for users seeking information for a suspected eating disorder. The screener meets those at risk 'where they are' (i.e. online) and may improve timely referrals to relevant services. This is of particular salience as face-to-face healthcare and traditional frontline interventions are disrupted, and we are challenged to re-design our practices to deliver diagnostic and treatment services in highly adaptive digital contexts.

Quantitative Torque Teno Virus Plasma DNA Assessments May Complement Donor-Derived Cell-Free DNA for Detection of Immunologic Events after Lung Transplantation

Torque Teno Virus (TTV) of the genus Anelloviridae , is an unenveloped, circular DNA virus with 23 genotypes that has been shown to be a potential surrogate biomarker for "Net State of Immunosuppression" in organ transplantation. Additionally, TTV levels have been shown to correlate with acute rejection (AR) and chronic lung allograft dysfunction (CLAD) as well as response to CoVid-19 vaccine in lung transplantation. Donor-derived cell-free DNA (dd-cfDNA) is a validated biomarker known to detect AR, CLAD and infection in lung transplant (LT) patients. We hypothesize that plasma TTV levels may complement dd-cfDNA in detecting different immunologic events after LT. We prospectively collected plasma samples from LT recipients from a single center LT program. dd-cfDNA was analyzed and clinical-pathologic events were carefully adjudicated and curated in all lung transplant recipients to define AR, CLAD, infection and stable samples. Herein, we analyze these plasma samples by Next Generation Sequencing (NGS) with quantification for TTV. Analyses will examine time-dependent performance characteristics of both dd-cfDNA fraction and quantified TTV levels for the endpoints AR, CLAD and infection with stable samples used as the comparison group. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cell death and barrier disruption by clinically used iodine concentrations.

Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I2), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I2 Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. FINDINGS: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). INTERPRETATION: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. FUNDING: None.

Too stressed to de-stress? The experience of work stress and recovery among attorneys during the COVID-19 pandemic

It is well-established that legal professionals experience high stress and often high rates of associated health problems. Much less is known about attitudes and behaviours around stress prevention in this occupation. Our study examined views of stress and recovery among 131 U.S. attorneys. In open-ended data, attorneys commonly expressed that their job is very demanding, and it impacts their health. Many respondents felt it was important to manage their stress but had difficulty doing so. Quantitative analyses showed that attitudes about stress (stress-related comparisons, viewing stress as achievement, stress-related impression management, and stigma around stress concerns) demonstrated several significant relationships with perceived stress, recovery experiences, remorse for relaxation, and work–family conflict. Our findings suggest that practical interventions to support the health and well-being of legal professionals may need to target the workload norms, as well as attitudes and beliefs about the normalness of high stress and insufficient recovery.

National Testing Assessment of Select Bacterial STIs During the COVID-19 Pandemic

Background. Chlamydia, gonorrhea, and syphilis infections rose in the US for 6 consecutive years before the COVID-19 pandemic. Patterns of sexually transmitted infection (STI) testing during the COVID-19 pandemic have yet to be fully assessed. Methods. We performed a retrospective study of STI testing in the Veteran's Health Administration (VHA) healthcare system during each calendar year 2019-2021 using electronic health record data. We determined the number of chlamydia (CT) and gonorrhea (GC), and syphilis tests performed overall and in demographic groups defined by age, birth sex, self-reported race, region, and HIV status. Results. VHA performed 202,503 CT tests, 201,314 GC tests and 250,790 syphilis tests in 2019, followed by a 23% and 25% decrease in 2020 for CT/GC and syphilis testing, respectively. We observed decreases among all subgroups defined by age, sex, race, and geography. Race groups with the biggest decreases in 2020 include Asian Americans (-28%) and Hawaiian and Pacific Islanders (-27%). By 2021, overall testing rates demonstrated a partial recovery to 89.8% of their 2019 levels. Testing rates in 2021 in rural/ highly rural residents remained 17% below baseline, compared with 10% for urban dwellers. Veterans living in the Northeast, South, or Midwest had the least recovery among geographic regions (16%, 11% and 11% below baseline, respectively). People with HIV experienced a decline in CT/GC testing of 15% but by the end of 2021 this had recovered to 1.9% below baseline. Women experienced both a steeper drop and a smaller recovery in CT and GC testing relative to men Conclusion. After dramatic reductions in STI testing during the COVID-19 pandemic, rates returned to near-baseline levels nationally by 2021. Testing rates have lagged in some patient groups, most notably rural and highly rural populations, women, and Black and Asian American Veterans, placing them at risk for disparities in STI diagnosis, and therefore treatment. Testing rates in Veterans under age 25 years have reached or exceeded pre-pandemic levels. (Figure Presented).

Public health and military health.

This paper summarizes the role of Public Health specialists within the UK Defence Medical Services (DMS). The armed forces have a need for expert advice on health improvement, health protection and healthcare public health. The first professor of military hygiene, Dr Edmund Parkes, was a leading pioneer in the public health movement of the late 19th century. Since then, the armed forces have evolved the term 'hygiene', though 'health', to 'well-being'. Military doctors with an interest in medical administration and the health of populations have longstanding links with their civilian peers, through the Society of Medical Officers of Health and its successor the Faculty of Public Health. The specialty of Public Health in the armed forces is multidisciplinary, following the same educational pathway as civilian peers. The speciality has made important contributions during global health emergencies including the Ebola outbreak in 2014 and the recent COVID-19 pandemic. Although a small cadre, within the DMS and in the UK Public Health workforce, they have an important role in keeping our armed forces ready for operations. We celebrate the 50th anniversary of the Faculty of Public Health and expect that the DMS will contribute to the further development of the specialty.

Trajectory of Functional Recovery from 6 to 12 Months in Persons Hospitalized for Severe SARS-CoV-2 Illness

Research Objectives To identify distinct post-acute COVID-19 phenotypes among adults hospitalized for severe SARS-CoV-2 infection and describe multidimensional outcomes and trajectories at 6 and 12 months post-hospitalization. Design Prospective, longitudinal data collection in functional, physical, cognitive, and psychological domains at 3, 6, and 12 months post-hospitalization. Retrospective data collection from the acute care and post-acute care settings. Setting Acute care and post-acute telephone follow-up. Participants English- and Spanish- speaking adults, with decision-making capacity, admitted for inpatient rehabilitation following inpatient rehabilitation for acute COVID-19 related illness (N = 61). Interventions N/A. Main Outcome Measures Physical, cognitive, and psychological symptoms;self-reported employment status and assistance with ADLs. Results Median age 60.8 years;59% male;72.1% white;72.1% non-Hispanic;26.2% preferred assessment in Spanish. 83% required mechanical ventilation in acute care. Comorbidities were common. We found a high prevalence of persistent symptoms at 6- and 12- months across physical, cognitive, and emotional health outcome domains. Three post-acute phenotypes were identified at 6 months;a "minimally symptomatic" subgroup with minimal symptom endorsement across all domains relative to other subjects (22.95%, n = 14), a “predominantly physical symptoms” subgroup (47.54%, n = 29), and a “globally symptomatic” subgroup (29.51%, n = 18). A similar pattern for phenotypes emerges at 12-months, with 67.21% of subjects falling into the same phenotype at both time points. In the Predominantly Physical Symptom phenotype, 31.0% declined into the Globally Symptomatic Phenotype and 10.3% improved. In the Globally Symptomatic phenotype, 11.1% of participants transitioned to the Minimally Symptomatic phenotype and 16.7% to the Predominantly Physical Symptom phenotype. Compared to premorbid level of employment (50.8%), 24.6% of participants were employed at 12-months. Phenotype at 6-months was a significant predictor of employment at 12-months (B = 2.26, p = .05, OR = 9.6). Conclusions Persons with severe COVID-19 illness experience persistent functional limitations and reduced employment up to 12 months post-hospitalization. Distinct recovery subgroups were found suggesting the need for comprehensive assessment and tailored treatment for recovery. Author(s) Disclosures The authors declare no relevant conflicts of interest.

Deuterated Drugs and Biomarkers in the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially identified in Wuhan (China) in December 2019, COVID-19 rapidly spread globally, resulting in the COVID-19 pandemic. Carriers of the SARS-CoV-2 can experience symptoms ranging from mild to severe (or no symptoms whatsoever). Although vaccination provides extra immunity toward SARS-CoV-2, there has been an urgent need to develop treatments for COVID-19 to alleviate symptoms for carriers of the disease. In seeking a potential treatment, deuterated compounds have played a critical role either as therapeutic agents or as internal MS standards for studying the pharmacological properties of new drugs by quantifying the parent compounds and metabolites. We have identified >70 examples of deuterium-labeled compounds associated with treatment of COVID-19. Of these, we found 9 repurposed drugs and >20 novel drugs studied for potential therapeutic roles along with a total of 38 compounds (drugs, biomarkers, and lipids) explored as internal mass spectrometry standards. This review details the synthetic pathways and modes of action of these compounds (if known), and a brief analysis of each study.

Assessment of Changes in Child and Adolescent Screen Time During the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Importance: To limit the spread of COVID-19, numerous restrictions were imposed on youths, including school closures, isolation requirements, social distancing, and cancelation of extracurricular activities, which independently or collectively may have shifted screen time patterns. Objective: To estimate changes in the duration, content, and context of screen time of children and adolescents by comparing estimates taken before the pandemic with those taken during the pandemic and to determine when and for whom screen time has increased the most. Data Sources: Electronic databases were searched between January 1, 2020, and March 5, 2022, including MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials. A total of 2474 nonduplicate records were retrieved. Study Selection: Study inclusion criteria were reported changes in the duration (minutes per day) of screen time before and during the pandemic; children, adolescents, and young adults (≤18 years); longitudinal or retrospective estimates; peer reviewed; and published in English. Data Extraction and Synthesis: A total of 136 articles underwent full-text review. Data were analyzed from April 6, 2022, to May 5, 2022, with a random-effects meta-analysis. Main Outcomes and Measures: Change in daily screen time comparing estimates taken before vs during the COVID-19 pandemic. Results: The meta-analysis included 46 studies (146 effect sizes; 29 017 children; 57% male; and mean [SD] age, 9 [4.1] years) revealed that, from a baseline prepandemic value of 162 min/d (2.7 h/d), during the pandemic there was an increase in screen time of 84 min/d (1.4 h/d), representing a 52% increase. Increases were particularly marked for individuals aged 12 to 18 years (k [number of sample estimates] = 26; 110 min/d) and for device type (handheld devices [k = 20; 44 min/d] and personal computers [k = 13; 46 min/d]). Moderator analyses showed that increases were possibly larger in retrospective (k = 36; 116 min/d) vs longitudinal (k = 51; 65 min/d) studies. Mean increases were observed in samples examining both recreational screen time alone (k = 54; 84 min/d) and total daily screen time combining recreational and educational use (k = 33; 68 min/d). Conclusions and Relevance: The COVID-19 pandemic has led to considerable disruptions in the lives and routines of children, adolescents, and families, which is likely associated with increased levels of screen time. Findings suggest that when interacting with children and caregivers, practitioners should place a critical focus on promoting healthy device habits, which can include moderating daily use; choosing age-appropriate programs; promoting device-free time, sleep, and physical activity; and encouraging children to use screens as a creative outlet or a means to meaningfully connect with others.

Retrospective spatial analysis of cases of COVID-19 in a single military accommodation block corridor, RMAS, January-March 21.

Shared ablutions and stairwells, corridor cross-ventilation and non-deliberate perflation (natural draft blowing through a space) are potential risk factors for COVID-19 transmission in corridor-based accommodation. This paper uses retrospective spatial analysis to identify potential built environmental risk factors during the January-March 2021 outbreak in Victory College, Royal Military Academy Sandhurst.Distance was measured in units of single room spacing. Odds, ORs and 95% CIs were calculated to identify and measure associations between distance from exposure and having COVID-19. Distance response trends were assessed using Pearson's χ2 for trend test. Linear relationships were tested using the t-test or rank-sum test.Stairwells and ablutions were not identified as likely sources of infection for all corridor occupants. Assuming occupants used their nearest ablutions, closer distance among those attributed to using ablutions 2 (one of four sets of ablutions), was identified as a risk factor (p=0.05). Testing distance response by χ2 linear trend testing showed a potential association between nearest adjacent positive room and COVID-19 (p=0.06), strongest if dominant air movement along the corridor length was from the left (p=0.10) compared with the right (p=0.24).Formal qualitative spatial analysis and environmental assessment of ventilation and air movement has a role in outbreak investigation in assessing factors related to the built environment. Environmental investigations would best inform outbreak investigations if undertaken contemporaneously. Pre-emptive and retrospective studies can help inform public health advice to military establishments in business continuity planning for isolation facilities, during outbreaks or in future development of the built environment.

A SPECTRUM OF CAUSES OF MOLECULAR INJURY IS DETECTED BY DONOR-DERIVED CELL-FREE DNA AFTER LUNG TRANSPLANT: PRELIMINARY EXPERIENCE

SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Donor-derived cell-free DNA (dd-cfDNA) is a promising plasma analyte for surveillance of rejection and lung transplant (LT) injury. Herein we report our preliminary real-world experiences in concert with standard of practice (SOP) assessments. METHODS: We performed a prospective, cross-sectional, cohort study of a clinically available dd-cfDNA test (the Prospera™ test, Natera, Inc.) combined with SOP clinical assessments − spirometry, fiberoptic bronchoscopy (FOB), donor-specific HLA antibodies (DSA). Single LT dd-cfDNA results were corrected (2X) for lung mass before analysis. Clinical-pathologic cohorts were assigned based on ISHLT guidelines for acute cellular rejection (ACR), uncomplicated chronic lung allograft dysfunction (U-CLAD), and either CoVid-19 or Non-CoVid-19 allograft infection. We also compared median dd-cfDNA fractions between patients experiencing allograft dysfunction (AD) (defined by ΔFEV1≥ -10%) vs stability (STA) and stratified by DSA status. Groups were analyzed by Mann-Whitney (p<0.05) and data expressed as median with 25-75% interquartile range (IQR). RESULTS: A total of 54 plasma samples from 42 unique LT recipients (Single=6, Double=36) were collected at Spectrum Health between November 2021 and February 2022. Primary diagnoses included chronic obstructive pulmonary disease (n=7), interstitial lung disease (n=31), CoVid-19 related ARDS (n=2), CF (n=1) and PAH (n=1). Matching histopathology was available for 68% of dd-cfDNA samples. dd-cfDNA fraction trended 2-fold higher in patient with ACR (1.59%, IQR: 0.09-3.57;n=3) and U-CLAD (1.88%, IQR: 0.88-3.32;n=4) than STA (0.86%, IQR: 0.21-1.62;n=14) patients. Patients with CoVid-19 had significantly higher dd-cfDNA fraction (6.91%, IQR: 2.41-9.77;n=4) than both STA (p=0.035) and NON-CoVid-19 infection cohorts (p=0.049). Although no antibody-mediated rejection (AMR) events were observed, dd-cfDNA fraction was significantly elevated in DSA(+) patients (2.75%, IQR: 1.72-6.25;n=8, class I (4) and II (4)) vs DSA(-) (1.035%, 0.04-1.64;n=46) cohorts (p=0.011). A trend was noted with elevated dd-cfDNA with AD (1.58%, IQR: 0.74-3.62;n=17) vs AS (1.05%, 0.66-1.79;n=37) (p=0.29). CONCLUSIONS: Our preliminary experience is consistent with prior studies, suggesting elevated dd-cfDNA fraction during LT allograft rejection and specific types of infection, in particular, CoVid-19. Of interest, dd-cfDNA detected potential occult molecular injury associated with anti-HLA DSA. CLINICAL IMPLICATIONS: dd-cfDNA fraction assessment after LT represents a valuable clinical tool for clinical surveillance of organ transplant health. DISCLOSURES: Employee relationship with Veracyte, Inc Please note: 2 years by Sangeeta Bhorade, value=Salary Removed 04/03/2022 by Sangeeta Bhorade Employee relationship with Natera Inc Please note: 2/22/22- present Added 04/03/2022 by Sangeeta Bhorade, value=Salary Employee relationship with Natera Please note: 05/2021-present Added 04/04/2022 by Kathryn Crabtree, value=Salary research relationship with United Therapeutics Please note: 2016- ongoing by Reda Girgis, value=Grant/Research research relationship with Pfizer Please note: 2014-2020 by Reda Girgis, value=Grant/Research Speaker/Speaker's Bureau relationship with Boehringher Ingelheim Please note: 2016-ongoing by Reda Girgis, value=Honoraria Speaker/Speaker's Bureau relationship with Genentech Please note: 2016-ongoing by Reda Girgis, value=Honoraria no disclosure on file for Cameron Lawson;No relevant relationships by Edward Murphy Employee relationship with Natera, Inc. Please note: 2020- present by David Ross, value=Salary

A comparison of CT-body composition measurements in non-cancer and cancer patients from a single UK centre

Objectives: Establish the prevalence of low skeletal muscle index and density in our population, by comparing age and sex matched cohorts of patients with and without cancer, using standardized methodology for CT-Body composition (CT-BC). Methods: A retrospective analysis of prospectively collected data. Patients admitted to our institution between 17th March 2020 - 1st May 2020, with confirmed coronavirus disease and imaging suitable for CT-BC (n=52), were age and sex matched with patients undergoing resection for colorectal cancer (n=52). Results: 104 patients were included in the final analysis. 43% (n=45) were male, 77% (n=80) were aged 65 years or older, 50% (n=50) were overweight (BMI ≥25) and 53% (n=55) were systemically inflamed (mGPS ≥1). The prevalence of a low SMI (56% vs. 65%) and low SMD (83% vs. 67%) was similar between cohorts. A low SMI and SMD were both associated with age (p<0.05 and p<0.01, respectively) on univariate analysis. On multivariate analysis, a low SMD was independently associated with age (OR 2.38 (1.34-4.22), p=0.003) and mGPS (OR 2.10 (1.20-3.68), p=0.01). Conclusions: In conclusion, the prevalence of a low SMI and low SMD was similar in non-cancer and cancer cohorts in our institution.

Leadership Beyond The Great Pause: Climate Change And Other Wicked Problems

The purpose of this paper is to provoke discussion and reflection in leaders with respect to the styles of leadership now required across sectors to deal with the significant wicked and super wicked problems now faced. Many business leaders now understand that their current management structures and leadership styles are not up to the challenge of successfully leading their organisations in a VUCA -world… and our climate crisis guarantees a VUCA -world for the foreseeable future. Yet, they do not know how to successfully deal with our climate crisis. They have never faced a situation like this before. There is no precedent or roadmap. Having excelled historically at solving linear-style problems, they want to know what to do to not only survive, but to thrive, in this new abnormal, full of wicked problems like climate change. A different form of leadership is required, one that is more agile, ambidextrous, andflexible. The application offutures thinking within organisations is a vital skill in accomplishing this, individually and cultural. The article applies scenarios developedfor a covid -world by Milojevic and Inayatullah (2021) to a -world that must confront climate change and other -wickedproblems. These scenarios are then interrogated to identify the benefits to leaders of unearthing the narratives that leaders and their organisations are unwittingly bound by. © 2022. Tamkang University, All rights reserved.

Global Changes in Child and Adolescent Physical Activity During the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Importance: Numerous physical distancing measures were implemented to mitigate the spread of the COVID-19 virus, which could have negatively affected child and adolescent physical activity levels. Objectives: To conduct a systematic review and meta-analysis of the literature that used validated measures to document changes in child and adolescent physical activity during the COVID-19 pandemic and to estimate whether changes in physical activity differed between participant-level, contextual, and methodological moderators. Data Sources: PubMed, PsycInfo, SPORTDiscus, Web of Science, Scopus, CINAHL, and MEDLINE were searched (from January 1, 2020, to January 1, 2022). A total of 1085 nonduplicate records were retrieved. Study Selection: Studies were included if they reported (1) changes in the duration of physical activity at any intensity for children or adolescents (age ≤18 years) comparing before and during the COVID-19 pandemic using validated physical activity measurement tools and were (2) from general population samples, (3) peer-reviewed, and (4) published in English. Data Extraction and Synthesis: A total of 126 articles underwent full-text review. Data were analyzed using a random-effects meta-analysis, which was conducted in January 2022. Main Outcomes and Measures: Change in the duration of engagement in physical activity at any intensity comparing before and during COVID-19. Results: Twenty-two studies including 46 independent samples and 79 effect sizes from 14 216 participants (median age, 10.5 years; range, 3-18 years) were included. The percentage change in the duration of engagement in total daily physical activity from before to during COVID-19 was -20% (90% CI, -34% to -4%). Moderation analyses revealed that changes were larger for higher-intensity activities (-32%; 90% CI, -44% to -16%), corresponding to a 17-minute reduction in children's daily moderate-to-vigorous physical activity levels. The reduction in physical activity was also larger for samples located at higher latitudes (37%; 90% CI, -1% to 89%) and for studies with a longer duration between physical activity assessments (25%; 90% CI, -0.5% to 58%). Conclusions and Relevance: Children and adolescents have experienced measurable reductions in physical activity during the COVID-19 pandemic. Findings underscore the need to provide bolstered access to support and resources related to physical activity to ensure good health and social functioning among children and adolescents during pandemic recovery efforts.