The more symptoms the better? Covid-19 vaccine side effects and long-term neutralizing antibody response (preprint)

Protection against SARS-CoV-2 wanes over time, and booster uptake has been low. This study explores the link between post-vaccination symptoms, biometric changes, and neutralizing antibodies (nAB) after mRNA vaccination. Data were collected from adults (n = 363) who received two doses of either BNT162b2 or mRNA-1273, with serum nAB concentration measured at 1 and 6 months post-vaccination. Daily symptom surveys were completed for six days starting on the day of each dose. Concurrently, objective biometric measurements, including skin temperature, heart rate, heart rate variability, and respiratory rate, were collected. We found that certain symptoms (chills, tiredness, feeling unwell, and headache) after the second dose were associated with increases in nAB at 1 and 6 months post-vaccination, to roughly 140-160% the level of individuals without each symptom. Each additional symptom predicted a 1.1-fold nAB increase. Greater changes in skin temperature and heart rate after the second dose predicted higher nAB levels. Skin temperature had a stronger predictive relationship for 6-month than 1-month nAB level. In the context of low ongoing vaccine uptake, our findings suggest that public health messaging could seek to reframe systemic symptoms after vaccination as desirable.

SwabExpress: An End-to-End Protocol for Extraction-Free COVID-19 Testing.

BACKGROUND: The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse-transcription PCR (RT-qPCR). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce. To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. METHODS: We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT-qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral inactivation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. RESULTS: After optimization, SwabExpress has a low limit of detection at 2-4 molecules/µL, 100% sensitivity, and 99.4% specificity when compared side by side with a traditional RT-qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. CONCLUSION: SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.

Maintaining High Quality Dosimetry Education in Radiation Oncology Medical Residency Amid and Post-COVID-19 Pandemic: A Reimagined Training Rotation

Background The Mayo Clinic radiation oncology medical residency program has maintained a dedicated medical dosimetry rotation since 1996. During this one-month rotation, residents practice and complete treatment plans under the supervision of certified medical dosimetrists. Skill development includes image fusions, contouring, treatment planning, and plan review all occurring in a one-on-one face-to-face educational environment. During the COVID-19 pandemic, our department incorporated dosimetry telework, and the rotation was modified into remote experience with an emphasis on creating enduring content while still maintaining a high-quality educational rotation. Methods In early 2020, the medical residency and dosimetry program leaders evaluated the state of the resident rotation with the goal of identifying areas of the rotation that could be made into enduring content, modernizing the objectives of the rotation, and adapting the face-to-face educational experience into a virtual environment. The new goals and platform were implemented in January 2022. Evaluations pre and post implementation were reviewed. Results After education committee review, goals and objectives were updated to reflect current practice. The rotation was restructured into a disease-site specific approach, with shared supervision by disease site, rather than a single dosimetry mentor. Site-specific standard of practice (SOP) documentation and twenty-four step-by-step tutorial videos teaching 3D and inverse treatment planning techniques were created. Virtual practice scenarios were created to ensure the appropriate breadth of experience. After onboarding for the rotation, residents reviewed site-specific SOP documentation and training tutorials while planning virtual cases independently, under disease site-specific dosimetry supervision. Virtual interactive plan review sessions of both practice and actual patients were performed through Microsoft Teams with supervising dosimetrists. Medical resident evaluation of the dosimetry rotation pre- and post- pandemic were collected via survey. Preliminary feedback on the recent implementation of enduring content and remote environment education have been positive, citing high quality content and satisfaction with virtual learning platform from residents. Raw data collection is currently in progress. Mentor feedback also cited improved rotation quality with enhanced efficiency of one-on-one instructional time. Discussion As the telework environment continues to evolve;the initial results of the restructured rotation present a positive outlook on the future of remote education and the success of enduring content from the perspective of both medical residents and dosimetrists. These results may also translate to the evolution of other aspects of the residency program. Further enhancements of the rotation including rotational assessments and attending physician interaction are planned for future resident rotations.

Predictors of long-term neutralizing antibody titers following COVID-19 vaccination by three vaccine types: the BOOST study.

As concerns related to the COVID-19 pandemic continue, it is critical to understand the impact of vaccination type on neutralizing antibody response durability as well as to identify individual difference factors related to decline in neutralization. This was a head-to-head comparison study following 498 healthy, community volunteers who received the BNT162b2 (n = 287), mRNA-1273 (n = 149), and Ad26.COV2.S (n = 62). Participants completed questionnaires and underwent blood draws prior to vaccination, 1 month, and 6 months after the vaccination series, and neutralizing antibody (nAB) titers at 1- and 6-months post vaccination were quantified using a high-throughput pseudovirus assay. Over 6 months of follow-up, nABs declined in recipients of BNT162b2 and mRNA-1273, while nABs in recipients of Ad26.COV2.S showed a significant increase. At the 6-month time point, nABs to Ad26.COV2.S were significantly higher than nABs to BNT162b2 and equivalent to mRNA-1273. Irrespective of follow-up timing, being older was associated with lower nAB for participants who received BNT162b2 and Ad26.COV2.S but not for those who received mRNA-1273. A higher baseline BMI was associated with a lower nAB for Ad26.COV2.S recipients but not for recipients of other vaccines. Women and non-smokers showed higher nAB compared to men and current smokers, respectively. The durability of neutralizing antibody responses differed by vaccine type and several sociodemographic factors that predicted response. These findings may inform booster recommendations in the future.

Clinical emergency care quality indicators in Africa: a scoping review and data summary.

OBJECTIVES: Emergency care services are rapidly expanding in Africa; however, development must focus on quality. The African Federation of Emergency Medicine consensus conference (AFEM-CC)-based quality indicators were published in 2018. This study sought to increase knowledge of quality through identifying all publications from Africa containing data relevant to the AFEM-CC process clinical and outcome quality indicators. DESIGN: We conducted searches for general quality of emergency care in Africa and for each of 28 AFEM-CC process clinical and five outcome clinical quality indicators individually in the medical and grey literature. DATA SOURCES: PubMed (1964-2 January 2022), Embase (1947-2 January 2022) and CINAHL (1982-3 January 2022) and various forms of grey literature were queried. ELIGIBILITY CRITERIA: Studies published in English, addressing the African emergency care population as a whole or large subsegment of this population (eg, trauma, paediatrics), and matching AFEM-CC process quality indicator parameters exactly were included. Studies with similar, but not exact match, data were collected separately as 'AFEM-CC quality indicators near match'. DATA EXTRACTION AND SYNTHESIS: Document screening was done in duplicate by two authors, using Covidence, and conflicts were adjudicated by a third. Simple descriptive statistics were calculated. RESULTS: One thousand three hundred and fourteen documents were reviewed, 314 in full text. 41 studies met a priori criteria and were included, yielding 59 unique quality indicator data points. Documentation and assessment quality indicators accounted for 64% of data points identified, clinical care for 25% and outcomes for 10%. An additional 53 'AFEM-CC quality indicators near match' publications were identified (38 new publications and 15 previously identified studies that contained additional 'near match' data), yielding 87 data points. CONCLUSIONS: Data relevant to African emergency care facility-based quality indicators are highly limited. Future publications on emergency care in Africa should be aware of, and conform with, AFEM-CC quality indicators to strengthen understanding of quality.

Incidence of Hyponatremia Among Critically Ill Patients With and Without COVID-19 Infection at a Community Teaching Hospital.

Background: Various studies have demonstrated the incidence of hyponatremia in patients with Coronavirus Disease 2019 (COVID-19); however, to our knowledge, no study has assessed the difference in the incidence of hyponatremia in patients with and without COVID-19. Purpose: To compare the incidence of hyponatremia in patients requiring intensive care unit (ICU) admission with and without COVID-19 infection. Methods: This was a single-center, retrospective cohort study of patients with a diagnosis of pneumonia from February 2019 to January 2020, or a diagnosis of COVID-19 from June 2020 to May 2021. Included patients were matched on age and sex. The primary outcome was the incidence of hyponatremia within 72 h of admission. Secondary endpoints collected included severity of hyponatremia, symptomatic hyponatremia, and lowest serum sodium. Results: There were 99 and 104 patients included in pneumonia and COVID-19 arms, respectively. Twenty-nine patients in the pneumonia group and 56 patients in the COVID-19 group had a sodium level <134 mEq/L (29% vs 56%, RR 1.84, P < .01). The mean lowest serum sodium within 72 h of admission was 136.9 mEq/L in the pneumonia group and 134.5 mEq/L in the COVID-19 group (P < .01). Other notable findings included days of mechanical ventilation (3 days vs 8 days, respectively; P < .01), downgrade from the ICU (74.8% vs 59.6%, P = .02), ICU length of stay (4 days vs 10 days, P < .01), hospital length of stay (6 days vs 14 days, P < .01), and mortality (16.2% vs 39.4%, P < .01). Conclusion: Among critically ill patients with COVID-19, the risk of hyponatremia was significantly greater than the risk in critically ill patients with pneumonia.

Veterinary Education's Role in the Opioid Epidemic: Integration of an Online Safe Opioid Prescribing Course into the Core Curriculum.

As the COVID-19 pandemic continues, the opioid epidemic has worsened. Opioid-related deaths continue to rise, and many of these deaths can be traced to a prescription opioid. Because veterinarians prescribe opioids, many organizations and federal agencies have called for increased veterinary education on the topic. In this teaching tip, we review the current literature surrounding the veterinary profession's link to the opioid epidemic and one potential way that educational institutions can successfully and efficiently incorporate safe opioid prescribing training into the curriculum using an online course.

The impact of the COVID-19 pandemic on a sample of US young adults who smoke cigarettes: A qualitative analysis.

INTRODUCTION: The ongoing COVID-19 pandemic has been associated with increased negative mood in youth, and a few reports of changes in tobacco use. We sought to increase the depth of knowledge on the effects of the pandemic on early young adult mood states, access to tobacco products and tobacco use behaviors, and knowledge of risks associated with tobacco use and COVID-19 by learning more about the lived experience of the pandemic among young adults early in their smoking trajectories. METHODS: Semi-structured qualitative interviews were conducted with 25 young adults ages 18-20 (M = 19) who smoked cigarettes daily or nearly every day and had used electronic cigarettes (ECs) on ≥ 2 occasions in their lifetime. RESULTS: Our results uncovered several themes: 1) The majority of teens experienced mental health disturbances as a result of the pandemic, which manifested as depression, anxiety, and/or acute loneliness due to social isolation; 2) tobacco purchasing behaviors sometimes changed, with both greater and less access reported among participants; 3) changes in tobacco use were also reported, with some reporting increases in use, others reporting decreases, and a few reporting quitting; and 4) while some youth reported that tobacco use could increase their risk related to COVID-19, the majority reported confusion and uncertainty about how tobacco use impacted their risk. CONCLUSIONS: The themes identified specific factors that may account for the heterogeneity of impacts of the pandemic on tobacco use, and highlight the value of qualitative work for centering the lived experience of youth for understanding larger trends in substance use.

The Impact of the COVID-19 Pandemic on a Sample of US Young Adults who Smoke Cigarettes: A Qualitative Analysis

Introduction The ongoing COVID-19 pandemic has been associated with increased negative mood in youth, and a few reports of changes in tobacco use. We sought to increase the depth of knowledge on the effects of the pandemic on early young adult mood states, access to tobacco products and tobacco use behaviors, and knowledge of risks associated with tobacco use and COVID-19 by learning more about the lived experience of the pandemic among young adults early in their smoking trajectories Methods Semi-structured qualitative interviews were conducted with 25 young adults ages 18-20 (M = 19) who smoked cigarettes daily or nearly every day and had used electronic cigarettes (ECs) on ≥ 2 occasions in their lifetime. Results Our results uncovered several themes: 1) The majority of teens experienced mental health disturbances as a result of the pandemic, which manifested as depression, anxiety, and/or acute loneliness due to social isolation;2) tobacco purchasing behaviors sometimes changed, with both greater and less access reported among participants;3) changes in tobacco use were also reported, with some reporting increases in use, others reporting decreases, and a few reporting quitting;and 4) while some youth reported that tobacco use could increase their risk related to COVID-19, the majority reported confusion and uncertainty about how tobacco use impacted their risk. Conclusions The themes identified specific factors that may account for the heterogeneity of impacts of the pandemic on tobacco use, and highlight the value of qualitative work for centering the lived experience of youth for understanding larger trends in substance use.

A Survey of Screen Media Access and Use in Primary School Children's Households.

Our primary aim was to gain a better understanding of current technology availability and use in the homes of primary school children. The online-accessible questionnaire was made available for families with a child enrolled at primary school, with over 300 families participating. The results suggest that it is common for children to be introduced to screen media early in life and that they watch a wide range of content. While many families have rules regarding their children's technology use, screen media is a significant part of their lives, with many children exceeding the recommended two hours of viewing per day. Future research could investigate whether media access and use differ between ethnic and socio-demographic groups, and whether changes have occurred as a result of the coronavirus pandemic.

Understanding the Impact of COVID-19 Pandemic on Central Line-Associated Bloodstream Infections (CLABSIs): Expanding Analysis to the Microbiologic Level

Background. Increases in central line-associated bloodstream infection (CLABSI) rates have been reported in association with the COVID-19 pandemic, particularly among Candida species and coagulase-negative Staphylococcal species (CoNS). We sought to further validate the impact of the COVID-19 pandemic on CLABSI trends and perform a microbiologic analysis. Methods. This is an IRB-approved retrospective analysis of CLABSIs across a network of 38 community hospitals in southeastern United States. CLABSI rates were compared between pre-pandemic (1/1/2018-3/30/2020) and pandemic periods (4/1/2020-12/31/2021). Regression models were developed to evaluate CLABSI incidence over time. Likelihood ratio tests were used to compare models that were exclusively time-dependent to segmented regression models that also accounted for the COVID-19 pandemic. Results. A total of 1,167 CLABSIs over 1,345,062 central line days were analyzed (Table 1). The mean monthly CLABSI rate per hospital increased from 0.63 to 1.01 per 1,000 central line days (p< 0.001) in the pandemic period (Table 1). CLABSIs secondary to Candida (0.16 to 0.33, p< 0.001), CoNS (0.09 to 0.22, p< 0.001), and Enterococcal species (0.06 to 0.18, p=0.001) increased, while Escherichia coli CLABSIs decreased (0.04 to 0.01, p< 0.001). Upon regression modeling, the COVID-19 pandemic was associated with increases in monthly CLABSI rates by Candida and Enterococcus species (Figure 1). In contrast, the changes in CoNS and Escherichia coli CLABSI rates were better explained by exclusively timedependent models (Figure 1;Table 2). Non-sustained changes in Staphylococcus aureus and Klebsiella pneumoniae CLABSI rates were also noted (Table 2). Gray areas denote COVID-19 pandemic period. Statistically significant level changes in CLABSI rates were observed among Candida and Enterococcus spp. (RR=1.92, CI 1.16-3.20 and 2.42, CI 1.09-5.38). Staphylococcus aureus CLABSI rates had a non-sustained but significant increase at the onset of COVID-19 (RR 2.20, CI 1.16-4.20). CoNS and E. coli rate changes occurred independent of COVID-19 (see Table 2). Conclusion. The COVID-19 pandemic was associated with substantial increases in CLABSIs, driven in part by Candida and Enterococcus species across this network of hospitals. However, the observed increase in CoNS CLABSIs and decrease in Escherichia coli CLABSIs appear to have occurred independently of COVID-19, which only became apparent upon regression analysis. Interpretation of pre-post statistics without assessment of pre-existing trends should be done cautiously. Additional analyses may help elucidate other factors influencing these CLABSI trends by organism.

Cost-Avoidance Associated with Active Stewardship of Remdesivir

Background. The COVID pandemic shifted antimicrobial stewardship resources at community hospitals. One reason for this shift was new COVID treatments, the first of which was remdesivir, which received initial emergency use authorization (EUA) for the treatment of COVID-19 in May 2020. The UNC Health Southeastern (UNC SEH) pharmacy director stewarded remdesivir by reviewing patients to ensure they met emergency use authorization (EUA) and guideline-based appropriateness criteria. The infectious diseases physician resolved any disputes regarding patient candidacy for remdesivir. The goal of remdesivir stewardship was to optimize care;however, the shift in workflow presented an unrecognized opportunity for stewards to reduce remdesivir costs. Methods. The percentage of COVID patient admissions receiving remdesivir at UNC SEH for calendar years 2020 and 2021 was benchmarked against 32 community hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) (Figure 1). UNC SEH purchasing data were used to calculate remdesivir expenditures for 2020 and 2021. Next, the anticipated cost if the hospital had prescribed remdesivir to the same percentage of admissions as the DASON mean was calculated. The difference was calculated to determine the cost avoidance achieved by having below average use of remdesivir (Table 1). Results. At UNC SEH, 28.1% of COVID admissions received remdesivir in 2020 and annual remdesivir expenditures were $693,680. In 2021, 47.45% of COVID-19 admissions received remdesivir and drug expenditures were $1,248,000. The DASON mean % of COVID admissions receiving remdesivir in 2020 was 44.08% and 60.07% in 2021. A total cost avoidance of $726,407 was calculated based on the hospital's below-benchmark use of remdesivir (Table 1). Conclusion. UNC SEH achieved significant cost-savings in 2020 and 2021 due to active remdesivir stewardship. The team created a patient-centered model that focused on using drugs for the right patients and the organization realized cost-savings while ensuring that patients received therapy in accordance with remdesivir EUAs and published guidelines.

Hospital COVID-19 Burden Impact on Inpatient Antibiotic Use Rates

Background. COVID-19 shifted antibiotic stewardship program resources and changed antibiotic use (AU). Shifts in patient populations with COVID surges, including pauses to surgical procedures, and dynamic practice changes makes temporal associations difficult to interpret. Our analysis aimed to address the impact of COVID on AU after adjusting for other practice shifts. Methods. We performed a longitudinal analysis of AU data from 30 Southeast US hospitals. Three pandemic phases (1: 3/20-6/20;2: 7/20-10/20;3: 11/20-2/21) were compared to baseline (1/2018-1/2020). AU (days of therapy (DOT)/1000 patient days (PD)) was collected for all antimicrobial agents and specific subgroups: broad spectrum (NHSN group for hospital-onset infections), CAP (ceftriaxone, azithromycin, levofloxacin, moxifloxacin, and doxycycline), and antifungal. Monthly COVID burden was defined as all PD attributed to a COVID admission. We fit negative binomial GEE models to AU including phase and interaction terms between COVID burden and phase to test the hypothesis that AU changes during the phases were related to COVID burden. Models included adjustment for Charlson comorbidity, surgical volume, time since 12/2017 and seasonality. Results. Observed AU rates by subgroup varied over time;peaks were observed for different subgroups during distinct pandemic phases (Figure). Compared to baseline, we observed a significant increase in overall, broad spectrum, and CAP groups during phase 1 (Table). In phase 2, overall and CAP AU was significantly higher than baseline, but in phase 3, AU was similar to baseline. These phase changes were separate from effects of COVID burden, except in phase 1 where we observed significant effects on antifungal (increased) and CAP (decreased) AU (Table). Conclusion. Changes in hospital AU observed during early phases of the COVID pandemic appeared unrelated to COVID burden and may have been due to indirect pandemic effects (e.g., case mix, healthcare resource shifts). By pandemic phase 3, these disruptive effects were not as apparent, potentially related to shifts in non-COVID patient populations or ASP resources, availability of COVID treatments, or increased learning, diagnostic certainty, and provider comfort with avoiding antibacterials in patients with suspected COVID over time. (Figure Presented).

Perception of Telehealth During the COVID-19 Pandemic Among Survivors of Gynecologic Cancer.

Our objective was to assess gynecologic cancer survivor preferences for telehealth cancer care. Gynecologic cancer survivors participating in a prospective cohort study were invited to complete a cross-sectional survey regarding their experience with and preferences for telehealth. Of 188 participants, 48.9% had undergone a telehealth visit since March 2020, and 53.7% reported a preference for exclusively in-person visits for their cancer care and surveillance. Furthermore, 80.5% of participants were satisfied with the telehealth care they received and 54.8% would recommend telehealth services to patients with similar conditions. Most participants thought a physical examination was critical to detecting recurrence, and concern that their provider may miss something during telehealth visits was greater among those who preferred in-person visits. With many gynecologic cancer survivors preferring in-person care, building a future care model that includes telehealth elements will require adaptations, careful evaluation of patient concerns, as well as patient education on telehealth.

Methods for detecting probable COVID-19 cases from large-scale survey data also reveal probable sex differences in symptom profiles.

Background: Daily symptom reporting collected via web-based symptom survey tools holds the potential to improve disease monitoring. Such screening tools might be able to not only discriminate between states of acute illness and non-illness, but also make use of additional demographic information so as to identify how illnesses may differ across groups, such as biological sex. These capabilities may play an important role in the context of future disease outbreaks. Objective: Use data collected via a daily web-based symptom survey tool to develop a Bayesian model that could differentiate between COVID-19 and other illnesses and refine this model to identify illness profiles that differ by biological sex. Methods: We used daily symptom profiles to plot symptom progressions for COVID-19, influenza (flu), and the common cold. We then built a Bayesian network to discriminate between these three illnesses based on daily symptom reports. We further separated out the COVID-19 cohort into self-reported female and male subgroups to observe any differences in symptoms relating to sex. We identified key symptoms that contributed to a COVID-19 prediction in both males and females using a logistic regression model. Results: Although the Bayesian model performed only moderately well in identifying a COVID-19 diagnosis (71.6% true positive rate), the model showed promise in being able to differentiate between COVID-19, flu, and the common cold, as well as periods of acute illness vs. non-illness. Additionally, COVID-19 symptoms differed between the biological sexes; specifically, fever was a more important symptom in identifying subsequent COVID-19 infection among males than among females. Conclusion: Web-based symptom survey tools hold promise as tools to identify illness and may help with coordinated disease outbreak responses. Incorporating demographic factors such as biological sex into predictive models may elucidate important differences in symptom profiles that hold implications for disease detection.

Impact of COVID-19 pandemic healthcare restrictions on utilisation and diagnostic yield of outpatient transthoracic echocardiograms.

BACKGROUND: During the COVID-19 pandemic, Kentucky prohibited elective medical procedures from 3/18/2020-4/27/2020. We sought to determine if cessation of elective procedures in Kentucky during the COVID-19 pandemic resulted in a decrease in the proportion of rarely appropriate outpatient transthoracic echocardiograms interpreted at the open echocardiography lab at Norton Children's Hospital. METHODS: A retrospective chart review was conducted comparing proportions of rarely appropriate outpatient paediatric transthoracic echocardiograms performed pre-COVID (3/21/2019-4/28/2019) and during COVID (3/19/2020-4/27/2020). Transthoracic echocardiogram indication was determined by chart review and echocardiogram reports. Indication appropriateness was evaluated using paediatric appropriate use criteria for initial outpatient transthoracic echocardiogram or CHD follow-up as applicable. RESULTS: Of transthoracic echocardiograms pre-COVID, 100 (37.7%) were rarely appropriate versus 18 (20.2%) during COVID. Pre-COVID, paediatric cardiologists tended to order fewer rarely appropriate transthoracic echocardiograms than paediatricians (35.9% versus 46.4%), although this difference was not statistically significant. Cardiologists ordered the majority of outpatient transthoracic echocardiograms during COVID (77/89, 86.5%), limiting the ability to compare transthoracic echocardiogram indications by provider type. There was no significant difference in diagnostic yield of initial outpatient transthoracic echocardiograms with (13.0%) abnormal studies pre-COVID versus 7 (15.5%) during COVID. CONCLUSION: While elective procedures were prohibited in Kentucky during the COVID-19 pandemic, a decrease in the proportion of rarely appropriate outpatient paediatric transthoracic echocardiograms was observed. There was no significant difference in diagnostic yield of initial outpatient transthoracic echocardiograms between time periods, suggesting that clinically significant echocardiogram findings were still detected despite more prudent utilisation of echocardiography during this time.

Clinical Features of the UK Myotonic Dystrophy Patient Registry

The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information about myotonic dystrophy type 1 (DM1) and type 2 (DM2). The registry was established in May 2012 with support from Muscular Dystrophy UK and the Myotonic Dystrophy Support Group and is coordinated Newcastle University. The registry aims to facilitate academic and clinical research, better characterise and understand DM, and disseminate information relating to upcoming studies and research advancements. The registry is used to capture longitudinal, selfreported data through an online portal available to patients and clinicians. Where specialised clinical or genetic information is required, the neuromuscular specialist involved in the patient's care can be invited to provide some additional information and the patient can select them from a pre-populated list at the registration stage. The registry is a Core Member of the TREAT-NMD Global Registries Network for DM1. Between May 2012 and January 2022, there were 834 patient registrations. On average there are 5 new registrations per month. For those reporting a clinical diagnosis, 96% have DM1 (of which 14% have a diagnosis of congenital DM) and 4% have DM2. Overall, 40% of patients have had genetic confirmation of their condition provided. The registry has previously supported almost 30 research enquiries to date. Since 2020, the registry has facilitated 11 enquiries including an industry enquiry, three COVID-19 surveys, and various surveys capturing information on dysphagia, pregnancy, patient preferences for future treatments and the patient/ caregiver experience. The registry continues to be a versatile, cost-effective research tool, helping facilitate and advance a range of DM research. Additional work continues to be done to improve reporting of genetic information on the registry and there are future data linkage plans between the registry and the Newcastle Research Biobank for Rare and Neuromuscular Diseases.

A Molecular Analysis of Memory B Cell and Antibody Responses Against Plasmodium falciparum Merozoite Surface Protein 1 in Children and Adults From Uganda.

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum (Pf) merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against Pf develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, full-length Pf merozoite surface protein 1 (PfMSP1FL), in individuals from a region in Uganda with high Pf transmission. Our results showed that PfMSP1FL-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ PfMSP1FL-specific classical MBCs. In contrast, anti-PfMSP1FL plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against PfMSP1FL, with broadening of the response against non-3D7 strains in adults. The B cell receptors encoded by PfMSP1FL-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable PfMSP1 protein. Proteomics analysis of PfMSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to B cell receptors of PfMSP1FL-specific MBCs, anti-PfMSP119 IgGs had high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the PfMSP1-specific humoral immune response with cumulative Pf exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of PfMSP1 variants by the plasma IgG repertoire.