Search for magnetic monopoles produced via the Schwinger mechanism.

Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism1. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist2. Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model3-7 but have never been experimentally detected. Searching for the existence of magnetic monopoles via the Schwinger mechanism has not yet been attempted, but it is advantageous, owing to the possibility of calculating its rate through semi-classical techniques without perturbation theory, as well as that the production of the magnetic monopoles should be enhanced by their finite size8,9 and strong coupling to photons2,10. Here we present a search for magnetic monopole production by the Schwinger mechanism in Pb-Pb heavy ion collisions at the Large Hadron Collider, producing the strongest known magnetic fields in the current Universe11. It was conducted by the MoEDAL experiment, whose trapping detectors were exposed to 0.235 per nanobarn, or approximately 1.8 × 109, of Pb-Pb collisions with 5.02-teraelectronvolt center-of-mass energy per collision in November 2018. A superconducting quantum interference device (SQUID) magnetometer scanned the trapping detectors of MoEDAL for the presence of magnetic charge, which would induce a persistent current in the SQUID. Magnetic monopoles with integer Dirac charges of 1, 2 and 3 and masses up to 75 gigaelectronvolts per speed of light squared were excluded by the analysis at the 95% confidence level. This provides a lower mass limit for finite-size magnetic monopoles from a collider search and greatly extends previous mass bounds.

Prevalence and predictors of cigarette smoking among people with HIV in Western Jamaica.

With highly active antiretroviral therapy, HIV infection has become a treatable chronic disease. However, modifiable risk factors such as cigarette smoking continue to impact the morbidity and mortality of people with HIV (PWH). We assessed the prevalence and factors associated with cigarette smoking and motivation to quit among PWH in Western Jamaica. A cross-sectional study was conducted in which 392 adults seeking HIV care at health facilities in Western Jamaica completed an interviewer-administered questionnaire. Current smoking prevalence among participants was 17.4%. Current smoking was significantly associated with being male (OR = 2.99), non-Christian/non-Rastafarian (OR = 2.34), living or working with another smoker (aOR =1.86), being moderate to severely depressed (OR = 3.24), having an alcohol drinking problem (OR = 1.84), and never being asked by a healthcare provider if they smoked (OR = 3.24). Among the PWH who currently smoke, 36.7% are moderately to highly dependent on nicotine. One-third of people who smoke (33.8%) started smoking for the first time after HIV diagnosis, while 66.2% initiated smoking before; 88% were willing to quit smoking. These findings provide baseline information for designing and implementing a comprehensive smoking cessation program that considers the needs of PWH in Jamaica, with the potential of becoming a replicable model for other HIV-specialized healthcare settings in the Caribbean.

Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction.

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.

Days alive and out of hospital for children born with single-ventricle heart disease.

BACKGROUND: This study describes the illness burden in the first year of life for children with single-ventricle heart disease, using the metric of days alive and out of hospital to characterize morbidity and mortality. METHODS: This is a retrospective single-centre study of single-ventricle patients born between 2005 and 2021 who had their initial operation performed at our institution. Patient demographics, anatomical details, and hospitalizations were extracted from our institutional single-ventricle database. Days alive and out of hospital were calculated by subtracting the number of days hospitalized from number of days alive during the first year of life. A multivariable linear regression with stepwise variable selection was used to determine independent risk factors associated with fewer days alive and out of hospital. RESULTS: In total, 437 patients were included. Overall median number of days alive and out of hospital in the first year of life for single-ventricle patients was 278 days (interquartile range 157-319 days). In a multivariable analysis, low birth weight (<2.5kg) (b = -37.55, p = 0.01), presence of a dominant right ventricle (b = -31.05, p = 0.01), moderate-severe dominant atrioventricular valve regurgitation at birth (b = -37.65, p < 0.05), index hybrid Norwood operation (b = -138.73, p < 0.01), or index heart transplant (b = -158.41, p < 0.01) were all independently associated with fewer days alive and out of hospital. CONCLUSIONS: Children with single-ventricle heart defects have significant illness burden in the first year of life. Identifying risk factors associated with fewer days alive and out of hospital may aid in counselling families regarding expectations and patient prognosis.

Exploring the existence, strength, and independence of relative age and maturation selection biases: a case study in Gaelic football talent development programmes.

BACKGROUND: Biological maturity and relative age player selection biases are well documented in youth sports. However, there has been limited examination of the relationship between these biases. AIM: This study investigated the presence, strength, and independence of relative age and biological maturity selection biases in Gaelic football. SUBJECTS AND METHODS: A total of 247 male players from U14 to U16, from two talent academies were assessed for relative age (decimal age (DA)) and biological maturity (discrepancy between biological and chronological age (BA-CA)). RESULTS: Relative age effects (RAE) were observed in the U14 (DA = 0.62, d = 0.40) and U15 squads (DA = 0.57. d = 0.26) only. A bias towards advanced maturity status was present at U14 (BA-CA = 0.60, d = 0.83), U15 (BA-CA = 0.78, d = 0.89), and U16 (BA-CA, d = 1.01). There was a trivial (U14, r(83) = -0.210; U15, r(88) = 0.060) and low (U16, r(76) = 0.352) correlation between relative age and maturity status. CONCLUSION: Substantial maturity selection biases and, to a lesser degree, relative age biases are evident in youth Gaelic football. Critically, these biases are independent constructs. Coaches and policy makers should be educated on the distinct influences of relative age and maturation, and on strategies to address these biases.

Rural-Urban Divide in the Prevalence and Correlates of Overweight and Obesity Among Women of Reproductive Age in Nigeria: A Multilevel Analysis of Repeated Cross-Sectional Data.

We examined rural and urban prevalence and correlates of overweight/obesity among women of reproductive age using survey data from Nigeria. Overweight and obesity prevalence increased from 16.1% and 6.1% in 2008 to 18.2% and 10.0% in 2018, while underweight prevalence consistently averaged at 12%. Regardless of the residential setting, age, marital status, education, occupation, wealth, and year were associated with higher risk of overweight/obesity, whereas breastfeeding showed a protective effect. Unique risk factors for overweight/obesity in urban areas were higher parity and female-headed households, while ethnicity, media exposure, and state of residence were unique risk factors in rural areas.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma.

INTRODUCTION: This exploratory analysis evaluated efficacy and safety data for enfortumab vedotin versus chemotherapy over a median follow-up of ∼2 years from EV-301. MATERIALS AND METHODS: Patients with locally advanced/metastatic urothelial carcinoma with prior platinum-containing chemotherapy and disease progression during/after programmed cell death protein 1/ligand 1 inhibitor treatment were randomized to enfortumab vedotin or chemotherapy (docetaxel, paclitaxel, vinflunine). Endpoints were overall survival (primary), progression-free survival (PFS), objective response, and safety. RESULTS: In total, 608 patients were included (enfortumab vedotin, n = 301; chemotherapy, n = 307). With a median follow-up of 23.75 months, 444 deaths had occurred (enfortumab vedotin, n = 207; chemotherapy, n = 237). Risk of death was reduced by 30% with enfortumab vedotin versus chemotherapy [hazard ratio (HR) 0.70 (95% confidence interval [CI] 0.58-0.85); one-sided, log-rank P = 0.00015]; PFS improved with enfortumab vedotin [HR 0.63 (95% CI 0.53-0.76); one-sided, log-rank P < 0.00001]. Treatment-related adverse event rates were 93.9% for enfortumab vedotin and 91.8% for chemotherapy; grade ≥ 3 event rates were 52.4% and 50.5%, respectively. Grade ≥ 3 treatment-related decreased neutrophil count (14.1% versus 6.1%), decreased white blood cell count (7.2% versus 1.4%), and anemia (7.9% versus 2.7%) were more common with chemotherapy versus enfortumab vedotin; maculopapular rash (7.4% versus 0%), fatigue (6.8% versus 4.5%), and peripheral sensory neuropathy (5.1% versus 2.1%) were more common with enfortumab vedotin. Of special interest adverse events, treatment-related skin reactions occurred in 47.3% of patients receiving enfortumab vedotin and 15.8% of patients receiving chemotherapy; peripheral neuropathy occurred in 48.0% versus 31.6%, respectively, and hyperglycemia in 6.8% versus 0.3%. CONCLUSIONS: After a median follow-up of ∼2 years, enfortumab vedotin maintained clinically meaningful overall survival benefit versus chemotherapy, consistent with findings from the EV-301 primary analysis; PFS and overall response benefit remained consistent. Adverse events were manageable; no new safety signals were observed.

Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet-Spengler Reaction for One-Pot Syntheses of Tetrahydroisoquinolines and Tryptolines.

Biocatalytic processes are highly selective and specific. However, their utility is limited by the comparatively narrow scope of enzyme-catalysed transformations. To expand product scope, we are developing biocompatible processes that combine biocatalytic reactions with chemo-catalysis in single-flask processes. Here, we show that a chemocatalysed Pictet-Spengler annulation can be interfaced with biocatalysed alcohol oxidation. This two-step, one-pot cascade reaction converts tyramine and aliphatic alcohols to tetrahydroisoquinoline alkaloids in aqueous buffer at mild pH. Tryptamine derivatives are also efficiently converted to tryptolines. Optimization of stoichiometry, pH, reaction time, and whole-cell catalyst deliver the tetrahydroisouinolines and tryptolines in >90 % and >40 % isolated yield, respectively, with excellent regioselectivity.

Prospective evaluation of pregnancy outcomes after gestational exposure to prazosin.

AIMS: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. The aim of this study was to assess the fetal and pregnancy safety associated with prazosin exposures in early pregnancy. METHODS: Subjects were 11 patients who took prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between 1 January 2000 and 31 December 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. RESULTS: It was found that 6/11 (54.5%) subjects did not report any adverse outcomes and experienced uneventful pregnancies. There were two miscarriages. Birthweights were within the normal range for the remaining nine pregnancies. Adverse events reported were consistent with background population expectation, including: one postpartum haemorrhage, one case of preeclampsia, one preterm birth, two NICU admissions, and two caesarean sections. CONCLUSIONS: For these 11 subjects, pregnancy outcomes after exposure to prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to prazosin while pregnant. Therefore, this study contributes valuable data towards monitoring safety of prazosin in pregnancy.

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Patterns of endocardial fibroelastosis without atrioventricular block in fetuses exposed to anti-Ro/SSA antibodies.

Anti-Ro/SSA-antibody-mediated endocardial fibroelastosis (EFE) without atrioventricular (AV) block at presentation is a rare cardiac phenotype. We report on 11 fetuses with this rare type of anti-Ro/SSA-antibody-mediated cardiac involvement, presenting with a distinctive echocardiographic pattern of EFE. Eleven fetuses with isolated EFE at presentation were included from four cardiac centers, and experienced fetal cardiologists reached a consensus regarding EFE location on echocardiography at presentation. Interval changes to subsequent fetal and postnatal echocardiograms were assessed to evaluate response to therapy. Echocardiographic markers of cardiac performance, including diastolic function and AV conduction, were reviewed. Ten fetuses were found to have EFE of the aortic root, proximal aorta and/or left ventricular outflow tract. In the same 10 cases, EFE of the pulmonary root, pulmonary artery and/or right ventricular outflow tract was identified. Six cases had atrial EFE and six had EFE of the crux. Four cases were known to be positive for anti-Ro/SSA antibodies prior to diagnosis, whereas, in the remaining seven, echocardiographic findings prompted testing, which was positive in all cases. The AV interval at presentation was normal in all cases, but one fetus subsequently developed AV block. Nine patients were treated with transplacental dexamethasone, five of which also received intravenous immunoglobulin (IVIG), and one received IVIG only. Of the 10 treated cases, six had improvement in EFE as shown by serial imaging and, in four cases, the severity was unchanged. All patients were liveborn. In our cohort, EFE of the aortic and pulmonary arteries and outflow tracts was nearly universal, and involvement of the atria and the crux of the heart was also common. The high survival rate and low burden of AV block are also suggestive of a distinct phenotype of anti-Ro/SSA-antibody-mediated cardiac disease with a favorable prognosis. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiac Magnetic Resonance Imaging to Determine Single Ventricle Function in a Pediatric Population is Feasible in a Large Trial Setting: Experience from the Single Ventricle Reconstruction Trial Longitudinal Follow up.

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function and flow quantification. There were 313 eligible SVRIII participants and 237 enrolled, ages ranging from 10 to 12.5 years. 177/237 (75%) participants underwent CMR. The most common reasons for not undergoing CMR exam were requirement for anesthesia (n = 14) or ICD/pacemaker (n = 11). A total of 168/177 (94%) CMR studies were diagnostic for RVEF. Median exam time was 54 [IQR 40-74] minutes, cine function exam time 20 [IQR 14-27] minutes, and flow quantification time 18 [IQR 12-25] minutes. There were 69/177 (39%) studies noted to have intra-thoracic artifacts, most common being susceptibility artifact from intra-thoracic metal. Not all artifacts resulted in non-diagnostic exams. These data describe the use and limitations of CMR for the assessment of cardiac function in a prospective trial setting in a grade-school-aged pediatric population with congenital heart disease. Many of the limitations are expected to decrease with the continued advancement of CMR technology.

Unfavourable beliefs about oral health and safety of dental care during pregnancy: a systematic review.

BACKGROUND: Oral conditions such as gingivitis and periodontitis are correlated with adverse pregnancy outcomes such as preeclampsia, preterm birth and low birth weight. Oral health-related unfavourable beliefs can have negative influences on oral health behaviours including hesitation in accessing preventative dental treatments and dental service utilization. The objective of this systematic review was to examine unfavourable beliefs that expectant or new mothers frequently hold about oral health and the safety of dental care during pregnancy. METHODS: An electronic database search on PubMed, Scopus, CINAHL, and MEDLINE (Ovid) followed by forward and backward citation tracing of the included studies was conducted. All English primary studies regardless of the year of publication were independently screened by two reviewers to identify studies addressing unfavourable beliefs about oral health and dental care during pregnancy. The CLARITY tool was applied to assess the risk of bias in the included studies. RESULTS: Out of a total of 5766 records, 39 quantitative and six qualitative studies met the inclusion criteria. The commonly held unfavourable beliefs were regarding the safety of dental services utilization and dental treatment procedures, the adverse impacts of pregnancy on oral health, and oral hygiene necessity during pregnancy. The most discussed unfavourable beliefs included "pregnant women lose their teeth because of pregnancy" (n = 18), "dental treatments are not safe and harm the fetus" (n = 17), and "the developing baby absorbs calcium from the mother's teeth" (n = 14). CONCLUSIONS: Unfavourable beliefs about oral health and dental care utilization are common among pregnant women and new mothers. The literature suggests that a low level of oral health knowledge and seeking information from social networks can contribute to such beliefs. This has implications for health promotion.

Do studies published in two leading reproduction journals between 2011 and 2020 demonstrate that they followed WHO5 recommendations for basic semen analysis?

STUDY QUESTION: Do publications that involve the interpretation of the results of a basic semen analysis, published in Human Reproduction and Fertility & Sterility between 2011 and 2020, give sufficient evidence in their methodology to demonstrate that they followed the technical methods recommended in the fifth edition of the World Health Organization (WHO) laboratory manual, entitled WHO Laboratory Manual for the Examination and Processing of Human Semen (WHO5)? SUMMARY ANSWER: Evidence of methodological agreement of studies with the WHO5 recommendations was low, despite 70% of papers stating that they followed WHO5 recommendations. WHAT IS KNOWN ALREADY: A basic semen analysis is currently an integral part of infertility investigations of the male, but method standardization in laboratories remains an issue. The different editions of the WHO manual for the basic semen analysis (WHO1-6) have attempted to address this by providing increasingly rigorous methodological protocols to reduce experimental error. However, to what extent these methods are followed by studies that involve the interpretation of the results of basic semen analysis remains unknown. STUDY DESIGN, SIZE, DURATION: A survey of the technical methods used to perform a basic semen analysis was conducted on studies published in two leading reproduction journals (Human Reproduction and Fertility & Sterility) between 2011 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: The literature search was performed on the electronic databases PUBMED and MEDLINE Ovid between January 2021 and March 2021. The MeSH terms included in the search were 'sperm concentration' OR 'sperm motility' OR 'sperm morphology' OR 'sperm vitality' OR 'male fertility' AND 'human spermatozoa' NOT 'animals'. A total of 122 studies were available for analysis. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 70% of the studies cited WHO5 in their methods section. Of the remaining studies, 10% cited the fourth edition of the WHO laboratory manual (WHO4), 7% cited both WHO4 and WHO5, 1% cited the third edition of the WHO laboratory manual (WHO3), and 12% did not cite the WHO at all. Overall methodological agreement with WHO5 recommendations was poor, with the main reason for this lack of agreement being that the research studies did not disclose specific details of the technical methods and equipment used. LIMITATIONS, REASONS FOR CAUTION: In the case of studies that did not disclose any specific technical methods that they used, we did not attempt to contact these authors and so were unable to confirm the agreement between their technical methods and WHO5 recommendations. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest there is an urgent need to develop strategies to address standardization in reporting the results of a semen analysis for publication. This is particularly timely given the recent publication of WHO6 and ISO standard 23162 for the basic examination of human semen. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this project. C.L.R.B., as an employee of the University of Dundee, serves on the Scientific Advisory board of ExSeed Health (from October 2021, financial compensation to the University of Dundee) and is a scientific consultant for Exscientia (from September 2021, financial compensation to the University of Dundee). C.L.R.B. has previously received a fee from Cooper Surgical for lectures on scientific research methods outside the submitted work (2020) and Ferring for a lecture on male reproductive health (2021). C.L.R.B. is Editor for RBMO. TRIAL REGISTRATION NUMBER: N/A.

Role of immune mediators in predicting hospitalization of SARS-CoV-2 positive patients.

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.

Legalisation of e-scooters in the UK: the injury rate and pattern is similar to those of bicycles in an inner city metropolitan area.

INTRODUCTION: Rental electric scooters (e-scooters) have become more available to the UK public following amendments to legislation in 2020 affecting rideshare schemes. Existing literature from outside the UK demonstrates a worrying trend of increasing injuries related to their use and non-compliance with suggested safety precautions. An e-scooter rideshare scheme trial began in Liverpool in October 2020. We intended to identify the musculoskeletal injury rate and describe the injuries sustained during this pilot. METHODS: Data were collected retrospectively from electronic patient records on all patients at a major trauma centre covering the whole of the Liverpool rideshare trial site presenting with e-scooter and bicycle musculoskeletal injuries between the trial start on 6th October 2020 and 5th May 2021 and between 6th March 2020 and 5th October 2020. Data on rental e-scooter use were obtained from the rideshare operator. RESULTS: Fifty-one patients sustained musculoskeletal injuries involving e-scooters during the trial period and six injuries before the trial. Two-thirds of injuries were on rental e-scooters. We calculate an orthopaedic injury rate of 26.1 injuries per million km on e-scooters and 24.1 injuries per million km on bicycles. Over 70% of e-scooter patients had upper limb injuries, over 50% had lower limb injuries and 15.7% of patients required surgery. CONCLUSIONS: We observed an increase in musculoskeletal injuries presenting to hospital during the e-scooter pilot. Rates of musculoskeletal injuries were comparable to rates of injuries sustained on bicycles. E-scooters should be regulated closely and further safety measures introduced to minimise the rate of injuries.

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021.

Importance: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. Objective: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. Design, Setting, and Participants: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. Exposures: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). Main Outcomes and Measures: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. Results: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). Conclusions and Relevance: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

Objectively measured waist circumference is most strongly associated in father-boy and mother-girl dyads in a large nationally representative sample of New Zealanders.

BACKGROUND: The prevalence of children with elevated weight or obesity is concerning for public health due to associated comorbidities. This study investigates associations between parental adiposity, physical activity (PA), fruit and vegetable consumption, and child adiposity and moderation by both child and parent gender. METHODS: Cross-sectional nationally representative data from the New Zealand Health Survey were pooled for the years 2013/14-2016/17. Parent and child surveys were matched resulting in 13,039 child (2-14 years) and parent (15-70 years) dyads. Parent and child, height (cm), weight (kg) and waist circumference (WC) were measured objectively. Height and weight were used to calculate BMI. Linear regression, accounting for clustered samples (b [95% CI]) investigated associations between parental characteristics and child BMI z-score and WC. Interactions and stratification were used to investigate effect moderation by parent gender, child gender, and parent adiposity. RESULTS: Parental PA and fruit and vegetable consumption were unrelated to child adiposity. Overall, higher parent BMI was related to a higher child BMI z-score (b = 0.047 [0.042, 0.052]) and higher parental WC was related to a higher child WC (0.15 [0.12, 0.17]). A three-way interaction revealed no moderation by parent gender, child gender, and parent BMI for child BMI z-score ((b = 0.005 [-0.017, 0.027], p = 0.318). However, a three-way interaction revealed moderation by parent gender, child gender, and parent WC for child WC (b = 0.13 [0.05, 0.22]). The slightly stronger associations were seen between father-son WC (b = 0.20 [0.15, 0.24]) and mother-daughter WC (b = 0.19 [0.15, 0.22]). CONCLUSIONS: The findings are highly relevant for those wishing to understand the complex relationships between child-parent obesity factors. Findings suggest that family environments should be a key target for obesity intervention efforts and show how future public health interventions should be differentiated to account for both maternal and paternal influences on child adiposity.

Multisystem Inflammatory Syndrome in Children: Survey of Protocols for Early Hospital Evaluation and Management.

OBJECTIVE: To describe the similarities and differences in the evaluation and treatment of multisystem inflammatory syndrome in children (MIS-C) at hospitals in the US. STUDY DESIGN: We conducted a cross-sectional survey from June 16 to July 16, 2020, of US children's hospitals regarding protocols for management of patients with MIS-C. Elements included characteristics of the hospital, clinical definition of MIS-C, evaluation, treatment, and follow-up. We summarized key findings and compared results from centers in which >5 patients had been treated vs those in which ≤5 patients had been treated. RESULTS: In all, 40 centers of varying size and experience with MIS-C participated in this protocol survey. Overall, 21 of 40 centers required only 1 day of fever for MIS-C to be considered. In the evaluation of patients, there was often a tiered approach. Intravenous immunoglobulin was the most widely recommended medication to treat MIS-C (98% of centers). Corticosteroids were listed in 93% of protocols primarily for moderate or severe cases. Aspirin was commonly recommended for mild cases, whereas heparin or low molecular weight heparin were to be used primarily in severe cases. In severe cases, anakinra and vasopressors frequently were recommended; 39 of 40 centers recommended follow-up with cardiology. There were similar findings between centers in which >5 patients vs ≤5 patients had been managed. Supplemental materials containing hospital protocols are provided. CONCLUSIONS: There are many similarities yet key differences between hospital protocols for MIS-C. These findings can help healthcare providers learn from others regarding options for managing MIS-C.