Intensive Care Consultant: Superhero or normal human being but more capable!

Submission content Introduction: Intensive care medicine has become an admired, loved, hated, and definitely more interesting Specialty due to a special situation (COVID-19) that exposed the training process to numerous criticisms, positives, and negatives, and this is how I believe we could improve our beloved world. Proposal: 1. Ideal training program from medical school to Certificate of Completion of Training (CCT): * Medical school: In their last year they should do more than 1 week in the Intensive Care Unit (ICU) * Stage 1: there should be a core surgical training of at least 6 months * Stage 2: there should be a rotation on Psychiatry of at least 4 weeks with on calls in ICU and 2 weeks in Palliative Care * Stage 3: acting as a consultant for the last six months on ST7 with backup from a formal consultant, and * Surgical training should be included in the possible dual or triple CCT 2. How would we be assessed? I agree with the Faculty of Intensive Care Medicine (FICM) staging program assessment, with some modifications: * As ST7 the trainee should act as a consultant with back support at least 50% of the stage and need to be evaluated by a Multi-Source Feedback (MSF). * Clinical Fellows should have a consultant as a Certificate of Eligibility for Specialist Registration (CESR) guide who establishes the equivalent stage of training supporting them and assessing them under the same model. * Changing the way, the General Medical Council (GMC) conducts the CESR application and making it really equivalent to the ICM training with the FFICM curriculum. 3. What do we need to be taught? * Hot topics for ICU (academic), * Overseas talks to share experiences, * Ultrasound (FUSIC), * Wellbeing strategies, * Leadership training * Psychiatric and physiological effects post ICU for patients and staff, * The administrative and political model of the National Health Service (NHS), and * Communication skills to establish excellent relationships with the other specialties. 4. What would our working life look like? * Normal day: 8 am to 3 pm * Midday shift: 1 pm to 8:30 pm * Night shift: 8 pm to 8:30 am * A rolling rota of 12 weeks with 2 weekends during this time 5. How would you produce Intensive Care Medicine (ICM) Consultants of the future who both love their job and their life: * Starting with less intense shifts, * More cordial relationships between the teams, * Supporting ICM trainees and Fellows going through their CESR pathway, * Making the training more attractive to either male-female doctors getting them involved in as many different specialties as ICM can cover, Conclusion(s): Having full-time ICM Consultants should be welcome in all ICUs in the country, which is not at the moment. This will definitely attract a lot of excellent doctors who are 100% focused on ICM.

Reproduction of the Control Group in REMDACTA Trial Using the Millennial Medical Record, an Electric Health Record Database, in Japan

Objectives: Developing a control group of a clinical trial using real world data is desirable and ethically sound despite challenges pertaining to internal validity. To examine the internal validity, we reproduced the control group in a Randomized Controlled Trial (RCT) using Electric Health Record (EHR) data and evaluated the difference between the outcome of the original trial and that of the reproduced analysis. Method(s): We selected an RCT, REMDACTA trial, that was performed to evaluate the efficacy of tocilizumab plus remdesivir against placebo plus remdesivir in patients with severe COVID-19 pneumonia. We reproduced its control group (patients with severe COVID-19 pneumonia taking only remdesivir), using Japanese EHR data, Millennial Medical Record provided by Life Data Initiative. Target patients for the main analysis were those prescribed remdesivir within 2 days after admission and diagnosed with COVID-19 (defined by ICD-10 code, U07.1) and/or with COVID-19 pneumonia (defined by diagnosis name). Patients in the sub analysis included only those with COVID-19 pneumonia diagnosis. Among the target patients, those undergoing image inspection, oxygen administration, and not taking any medicines for pneumonia before the first remdesivir prescription were eligible for the analyses. Median length of stay was compared in the reproduced group and in REMDACTA trial. Result(s): The database included 676 and 110 target patients for the main and sub analyses, respectively. However, only 57 and 14 patients met the eligibility criteria for the main and sub analyses, respectively. The reduction in the number of patients is attributed to the criteria of image inspection and oxygen administration. Median length of stay in the reproduced group were 13 and 11 days in the main and sub analyses, respectively. In REMDACTA trial, 95% CI of median time was 11.0-16.0. Conclusion(s): We successfully reproduced the median time of the control group by EHR data.Copyright © 2023

Barriers to in-Person Focus Group Participation during the Third-Year of COVID-19 Pandemic: A Case Study of Colorectal Cancer (CRC) Screening in Underrepresented Groups

Objectives: In the process of conducting research to understand barriers to colorectal cancer (CRC) screening in underrepresented groups such as Blacks and Hispanics, it became evident that there were also barriers to recruitment in this population. This study assesses the challenges faced in recruitment of focus group participants regarding CRC screening practices among underrepresented groups. Since the COVID-19 pandemic, qualitative research participants have primarily been interviewed through online video or audio interactions. However, as restrictions on in-person interactions have been lifted, in-person focus groups are being increasingly considered. Method(s): The study investigators began recruitment through community health workers in August 2022, when COVID-19 vaccines were available for all adults (age>18 years). Eligible individuals were: age 45-75, Black or Hispanic, with Medicaid or no insurance, and no family history of CRC or diagnosis of certain colon-related diseases. We combined in-person and virtual recruitment strategies, including posting flyers in communities, advertising our study at health fairs, and on social media. Participants would receive a $50 gift card. Result(s): Fifty-five met the eligibility criteria among 144 respondents, and 45 subjects (29 women and 16 men) agreed to be contacted. An average of 2.5 attempts were made per eligible subject. Unfortunately, we were able to recruit only four women (3 Hispanic and one non-Hispanic black). Traveling to the research site was a barrier to participation. Many subjects (49%) requested virtual participation (online video or audio interactions);some declined because the topic was too sensitive (considered taboo), and eligible men were reluctant to participate in-person. Conclusion(s): The requirement of in-person participation affected our recruitment goals, suggesting that COVID-19 has shifted the preferences of research participants to virtual interaction. In response to the eligible participant preferences, the study protocol has been revised to re-contact patients and schedule virtual FG sessions.Copyright © 2023

Preliminary results from phase 2 of CC-92480- MM- 001: Mezigdomide plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

In phase 1 of CC-92480- MM- 001 (NCT03374085), the recommended phase 2 dose (RP2D) of mezigdomide plus dexamethasone (MEZI-d) was selected at 1 mg once daily for 21/28 days. Here we report preliminary results from the MEZI-d dose-expansion cohort in patients with heavily pretreated RRMM. Key eligibility criteria were: RRMM;>=3 prior lines of therapy;disease progression <=60 days of last myeloma therapy;refractoriness to lenalidomide/pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody. Oral mezigdomide 1 mg was given on days 1-21 of each 28-day cycle, plus weekly dexamethasone (40 mg;20 mg if >75 years of age). Primary objective was to evaluate efficacy (overall response rate [ORR]);secondary objectives included safety/tolerability and additional efficacy assessments. Pharmacodynamics was an exploratory objective. As of 16/Sep/2022, 101 patients had received MEZI-d at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years;39.6% of patients had plasmacytomas and 37/101 patients had high-risk cytogenetics (56/101 not evaluable). Median number of prior regimens was 6 (3-15);prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%). All patients were refractory to last myeloma regimen and triple-class refractory. Median follow-up was 7.5 (0.5-21.9) months, with a median of 4 (1-20) cycles;10.0% of patients continued treatment;progressive disease was the main reason for discontinuation (60.4%). ORR was 40.6% for all patients. Whilst data are not mature yet, median PFS was 4.4 (95% CI 3.0-5.5) months and median duration of response was 7.6 (95% CI 5.4-9.5) months. ORR was 30.0% in patients with plasmacytomas (N = 40) and 50.0% in patients with prior anti-BCMA therapy (N = 30). Ninety-one (91.1%) patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). Most frequent hematologic grade 3/4 TEAEs were neutropenia (75.2%), anaemia (35.6%), and thrombocytopenia (27.7%);34.7% of patients had grade 3/4 infections, including grade 3/4 pneumonia (15.8%) and COVID-19 (7.0%). Occurrence of other grade 3/4 non-hematologic TEAEs was generally low. Due to TEAEs, 76.2% and 29.7% of patients had mezigdomide dose interruptions and reductions, respectively;90.1% of patients discontinued mezigdomide. Mezigdomide induced substrate degradation and increases in activated and proliferating T cells in patients, including those directly refractory to pomalidomide-based therapies. MEZI-d had a manageable safety profile with encouraging efficacy in patients with triple-class refractory RRMM, including patients with prior BCMA-targeted therapies. These results strongly support the continued development of mezigdomide in MM, and especially in combination.

Lung cancer screening use before & during the COVID-19 pandemic in the US: Population-based evidence from 2019-2021

Introduction: Lung cancer is the leading cause of cancer-related death in the US with an estimated 236,740 new cases and 130,180 deaths expected in 2022. While early detection with low-dose computed tomography reduces lung cancer mortality by at least 20%, there has been a low uptake of lung cancer screening (LCS) use in the US. The COVID-19 pandemic caused significant disruption in cancer screening. Yet, little is known about how COVID-19 impacted already low use of LCS. This study aims to estimate LCS use before (2019) and during (2020 and 2021) the COVID-19 pandemic among LCS-eligible population in the US. Method(s): We used population-based, nationally representative, cross-section data from the 2019 (n=4,484), 2020 (n=1,239) and 2021 (n=1,673) Behavioral Risk Factor Surveillance System, Lung Cancer Screening module. The outcome was self-reported LCS use among eligible adults in the past 12 months. For 2019 and 2020, the eligibility was defined based on US Preventive Services Task Force (USPSTF) initial criteria-adults aged 55 to 80 years old, who were current and former smokers (had quit within the past 15 years) with at least 30 pack years of smoking history. For 2021, we used the USPSTF updated criteria- adults aged 50 to 80 years, current and former smokers (who had quit within the past 15 years) with at least 20 pack years of smoking history. We applied sampling weights to account for the complex survey design to generate population estimates and conducted weighted descriptive statistics and logistic regression models. Result(s): Overall, there were an estimated 1,559,137 LCS-eligible respondents from 16 US states in 2019 (AZ, ID, KY, ME, MN, MS, MT, NC, ND, PA, RI, SC, UT, VT, WV, WI), 200,301 LCS-eligible respondents from five states in 2020 (DE, ME, NJ, ND, SD), and 668,359 LCS-eligible respondents from four states in 2021 (ME, MI, NJ, RI). Among 2,427,797 LCS-eligible adults, 254,890;38,875;and 122,240 individuals reported receiving LCS in 2019, 2020 and 2021, respectively. Overall, 16.4% (95% CI 14.4-18.5), 19.4% (95% CI 15.3-24.3), and 18.3% (95% CI 15.6-21.3) received LCS during 2019, 2020, and 2021, respectively. In all years, the proportion of LCS use was higher among adults aged 65-74, insured, those with fair and poor health, lung disease and history of cancer (other than lung cancer). In 2020, a higher proportion of adults living in urban areas reported receiving LCS compared to those living in rural areas (20.36% vs. 12.7%, p=0.01). Compared to non-Hispanic White adults, the odds of receiving LCS was lower among Hispanic adults and higher among Non-Hispanic American Indian/Alaskan Native adults in 2020 and 2021, respectively. Conclusion(s): LCS uptake remains low in the US. An estimated 2,011,792 adults at high-risk for developing lung cancer did not receive LCS during 2019, 2020 and 2021. Efforts should be focused to increase LCS awareness and uptake across the US to reduce lung cancer burden.

Identifying Clinical Subtypes of Long COVID: An Unsupervised Machine Learning Approach

Objectives: The symptoms of patients with post-acute COVID-19 syndrome are heterogenous, impact multiple systems, and are often non-specific. To better understand the symptomatic profile of this population, this study used real-world data and unsupervised machine learning techniques to identify distinct groupings of long COVID patients. Method(s): Children/adolescents (age 0-17) and adults (age 18-64 and >=65) with >=2 primary diagnoses for U09.9 "Post COVID-19 condition" from 10/01/2021 (ICD-10 code introduction) until 03/31/2022 were selected from Optum's de-identified Clinformatics Data Mart Database, with the first diagnosis deemed index. Included patients had >=1 diagnosis for COVID-19 at least 4 weeks before index and continuous enrollment during the 12 months prior to index. Diagnoses recorded +/-2 weeks from index that were not present prior to the initial COVID-19 diagnosis were captured and used as patient features for k-means clustering. Final cluster assignments were selected based on silhouette coefficient and clinical relevancy of groupings. Result(s): 3,587 patients met eligibility criteria, yielding three clusters. Concurrent symptom domains surrounding index included breathing, fatigue, pain, cognitive, and cardiovascular diagnoses. The first cluster (N=2,578, 71.8%) was characterized by patients with only a single symptom domain (33% breathing, 33% cardiovascular, 20% fatigue, 11% cognitive). The second cluster (N=651, 18.1%) all presented with breathing symptoms accompanied by one additional domain (cardiovascular 40%, fatigue 28%, pain 18%). The final cluster (N=358, 9.9%) experienced breathing symptoms accompanied by two additional domains (fatigue and cardiovascular 34%, cardiovascular and cognitive 34%). Cluster 3 was slightly older than clusters 1 or 2 (mean age 66 vs. 58 years, respectively). Conclusion(s): Unsupervised machine learning identified distinct groups of long COVID patients, which may help inform multidisciplinary care needs. Our analysis suggests that many patients with long COVID may experience symptoms from only a single domain, and multi-system illness may generally include breathing complications accompanied by fatigue and/or cardiovascular complications.Copyright © 2023

Characteristics of Patients Diagnosed with Long COVID: Early Findings from Real-World Data

Objectives: While persistent and relapsing symptoms of COVID-19 are increasingly documented, limited data exist on the post-acute population. The objective of this analysis is to identify the characteristics of patients diagnosed with long COVID using real-world data. Method(s): Children/adolescents (age 0-17) and adults (age 18-39, 40-64 and >=65) with >=2 primary diagnoses for U09.9 "Post COVID-19 condition" from 10/01/2021 (ICD-10 code introduction) until 03/31/2022 were selected from Optum's de-identified Clinformatics Data Mart Database, with the first diagnosis deemed index. Included patients had >=1 diagnosis for COVID-19 and continuous enrollment 12 months prior to index (baseline). To ensure alignment with most institutional definitions, >=4 weeks between initial COVID-19 infection and index was required. Diagnoses recorded +/-2 weeks from index that were not present prior to the initial COVID-19 diagnosis were summarized. Newly prescribed treatments and total medical costs were evaluated during the month following index (continuous enrollment required). Result(s): 3,587 patients met eligibility criteria (mean age 59.02, 57.56% female) with a median time from initial COVID-19 infection to long COVID diagnosis of 83 days (IQR: 46-201 days). The most common concurrent diagnoses included breathing complications such as dyspnea (20.38%) and respiratory failure (15.23%);malaise and fatigue (15.31%);symptoms related to cognitive functioning/anxiety (11.35%);and chest pain (7.67%). Children/adolescents had the highest prevalence of chest pain, while patients >=65 years of age had the highest prevalence of issues with coordination. The average total medical cost during the month following long COVID diagnosis was $4,267 (SD $14,662), with common prescriptions including albuterol (4.42%), prednisone (3.51%), and methylprednisolone (2.01%). Conclusion(s): This retrospective analysis confirms clinically documented symptoms of long COVID in a large, real-world population. Once more data become available, further research on the long term economic and clinical outcomes among patients diagnosed with post-acute COVID-19 syndrome are warranted.Copyright © 2023

Upskilling haematological services for WGS and germline assessments through a regional skin biopsy training programme

NHS England Genomics introduced whole genome sequencing (WGS) with standard-of- care (SoC) genetic testing for haemato-oncology patients who meet eligibility criteria, including patients with acute leukaemia across all ages, and exhausted SoC testing. Alongside, the role of germline mutations in haematological cancers is becoming increasingly recognised. DNA samples are required from the malignant cells (somatic sample) via a bone marrow aspirate, and from non-malignant cells (germline sample) for comparator analysis. Skin biopsy is considered the gold-standard tissue to provide a source of fibroblast DNA for germline analysis. Performing skin punch biopsies is not within the traditional skillset for haematology teams and upskilling is necessary to deliver WGS/germline testing safely, independently and sustainably. A teaching programme was designed and piloted by the dermatology and haematology teams in Sheffield and delivered throughout the NHS trusts in North East & Yorkshire Genomic Laboratory Hub. The training programme consisted of a 90-min session, slides, video and practical biopsy on pork belly or synthetic skin, designed to teach up to six students at one time. To disseminate best practice, the standard operating procedure and patient information used routinely in Sheffield were shared, to be adapted for local service delivery. From January 2021 to December 2022, 136 haematology staff from 11 hospitals, including 34 consultants, 41 registrars, 34 nurses and 8 physician associates, across the NEY GLH region completed the skin biopsy training programme. Feedback from the course was outstanding, with consistently high scores in all categories. Practical components of the course were especially valued;98.6% (71/72) trainees scored the practical element of the programme a top score of 5 out of 5, highlighting that despite the challenges of delivering face-to- face teaching due to COVID-19, teaching of practical skills was highly valued;training in this way could not have been replicated virtually. Costs of the programme have been approximately 16 000, including consultant input and teaching/educational materials. Recent support has been provided by a separately funded Genomic Nurse Practitioner (GNP), with succession planning for the GNP to take over leadership from the consultant dermatologist. Plans are in place to use the remaining budget to disseminate the programme nationally. Our training programme has shown that skin biopsy can be formally embedded into training for haematology consultants, trainees, nursing team, and physician associates. Delivery of training can be effective and affordable across regional GLHs with appropriate leadership and inter-speciality coordination, and ultimately sustainable with specialist nursing staff, including GNPs.

Public Health Impact of UK COVID-19 Booster Vaccination during Omicron Predominance

Objectives: To estimate the public health impact of COVID-19 booster vaccination in the UK during Omicron predominance, and to explore the impact in counterfactual scenarios with different booster eligibility or uptake. Method(s): A dynamic transmission model was developed to compare public health outcomes for actual and hypothetical UK Spring and Autumn 2022 booster programs. Outcomes were projected over an extended time horizon from April 2022-April 2023, assuming continued Omicron predominance as in Jan-Mar 2022. Health outcomes included averted cases, hospitalizations, long COVID cases, and deaths. NHS resource use outcomes were averted general ward and intensive care unit bed days and general practitioner visits. Patient productivity loss outcomes considered productive days lost for those in and outside the paid work force. Analyses used publicly available data. Result(s): Model output suggested that actual Spring and Autumn 2022 programs, which offered boosters to older adults and vulnerable populations, would avert approximately 716,000 hospitalizations, 1.9M long COVID cases and 125,000 deaths compared to not offering boosters in Spring and Autumn 2022. In a scenario that broadened eligibility to individuals aged >=5 years, an estimated 1.6M hospitalizations, 8.3M long COVID cases, and 222,000 deaths were averted. A scenario assuming broadened eligibility and increased uptake produced the greatest benefit among scenarios analyzed: 1.6M hospitalizations, 9.2M long COVID cases, and 228,000 deaths averted;and 953M productive days saved. Scenarios offering boosters only to high-risk individuals (aged >=5 years) were also estimated to improve benefit relative to actual programs. High-risk-only programs assuming increased uptake provided about half to two-thirds of the benefit estimated for programs assuming broadened eligibility and increased uptake. Conclusion(s): UK booster vaccination programs were estimated to provide substantial benefit to public health during Omicron predominance. Public health benefits could be maximized by broadening booster eligibility to younger age groups and increasing uptake.Copyright © 2023

Digital Contact Tracing for COVID-19: Overview of Existing Systems and Framework for Future Innovation

Background: The COVID-19 pandemic catalyzed innovation in infection control measures, including widespread deployment of digital contact tracing systems. However, these technologies were not well understood by the general public and were complex for the public health community to implement, hampering adoption. Objective(s): To provide an overview of existing digital contact tracing systems, creating a framework for understanding design elements that impact their effectiveness as public health tools and offering a rubric for decision-makers to evaluate different systems for selection and implementation. Method(s): Scientific literature and publicly available information from relevant health authorities and other stakeholders was reviewed. Information was synthesized to develop a conceptual framework explaining how key design elements impact effectiveness of digital contact tracing systems and highlighting opportunities for future improvement. Result(s): A range of digital contact tracing interventions were deployed by governments worldwide and several professional sports leagues. Key design elements of the systems include: (1) data architecture (i.e., centralized versus decentralized systems, impacting privacy guarantees and data availability);(2) proximity detection technology (e.g., type of device signaling);(3) alert logic and timing (e.g., time- and distance-based criteria affecting sensitivity and specificity of alerts;real-time proximity alerts and/or bidirectional contact tracing, determining scope of infection prevention);(4) population (eligibility and availability);and (5) the structural and public health context of intervention (e.g., availability and timeliness of testing). Several systems demonstrated effectiveness in preventing transmission during COVID-19, though numerous limitations have also been documented in the literature. Conclusion(s): Digital contact tracing systems have the potential to mitigate the economic and public health impact of future infectious disease outbreaks, reducing community transmission and detecting potential cases earlier in the disease course. Lessons learned from solutions deployed during the COVID-19 pandemic provide an opportunity to improve multiple aspects of these systems, enhancing preparedness for future outbreaks.Copyright © 2023

Comparison of disinfection quality in nurseries of Nanjing during 2019 - 2021

Objective To analyze the disinfection quality and influencing factors of nurseries in Nanjing during 2019-2021 so as to provide a scientific basis for optimizing preventive disinfection strategies and measures in nurseries. Methods Environmental samples from 389 nurseries in Nanjing from January 2019 to December 2021 were tested and the change of disinfection quality qualification rate was compared. Results The overall disinfection qualification rate of nurseries of year 2019-2021 were 96.32% 95.85% and 94.60% respectively showing a downward trend χ2trend = 8.67 P<0.05 . Specifically disinfection qualification rate of object surfaces staff hands and tableware showed a downward trend while the disinfection qualification rate of dynamic air showed an upward trend and the differences were statistically significant χ2trend = 23.17 12.32 5.37 21.48 P<0.05 . The total qualification rate of disinfection in Jiangning and Liuhe districts increased during 2019-2021 χ2trend = 21.46 24.05 P<0.05 . Conclusion Disinfection quality of nurseries in Nanjing has declined by year during 2019-2021 especially the object surfaces and staff hands. It is urgent to optimize and refine the strategies and measures for preventive disinfection in nurseries strengthen the training of personnel on disinfection knowledge and ensure the quality of disinfection in nurseries. © 2023 Chinese Journal of General Surgery. All rights reserved.

Evaluation of the Updated French Autorisation D'Acces Precoce (AAP) Early Access Authorization Pathway

Objectives: To evaluate products reviewed by the Transparency Committee (TC) of the Haute Authorite de Sante (HAS) under the Autorisation d'Acces Precoce (AAP) Early Access Authorization (EAA) pathway and investigate any trends. Method(s): All 97 AAP submissions are publicly available from HAS and were evaluated on or before January 4th, 2023. The TC's opinion was reviewed to obtain the outcome, decision date, therapeutic area, and reasons for rejection. Results were tabulated and descriptive statistics were compiled. Result(s): In total, 79 of the 97 (81%) submissions evaluated were approved for EAA, including renewals of previously granted authorization (6 of 79);18 were rejected. Of the 97 submissions, 35% were indicated for the treatment of solid cancers, 14% for haematological cancers, 10% for ultra-rare diseases, 10% for infectious diseases, 4% for rare diseases, 4% for autoimmune diseases, 4% for skin diseases, and 2% for weight management. Notable approved submissions including those indicated for rare diseases, cancer, autoimmune diseases, and COVID-19, with 93%, 90%, 75%, and 63% of these submissions being granted EAA, respectively. Across the 18 unsuccessful submissions, the main reasons cited for rejection were insufficient efficacy and safety data (78%), lack of innovation compared to existing treatment options (61%), the availability of existing treatment options (56%), and the treatment not being rare enough to qualify for special consideration (28%). Conclusion(s): Since its inception in July 2021, the AAP has proven to be a popular program. As awareness of the program grows and more information becomes available about its benefits and eligibility criteria, it is likely that the number of submissions will continue to increase. However, given the link between submission success and the quality of available data (including a data collection plan), it is recommended manufacturers provide robust evidence to bolster their submissions.Copyright © 2023

Updated Real-World Safety of the Pfizer-BioNTech COVID-19 Vaccine in Pregnancy: Data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry

Purpose: Preliminary data indicate that pregnant women infected with COVID-19 are at increased risk of pregnancy complications (US Centers for Disease Control and Prevention, October 2022). Information on the real-world safety of COVID-19 vaccination in pregnancy is essential. We sought to describe preliminary results for pregnancy status among pregnancy registry participants enrolled in an ongoing safety study of the Pfizer-BioNTech COVID-19 vaccine to date. Method(s): This study uses data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry as part of the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) which enrolls pregnant women residing in the US or Canada. Data are captured through maternal interviews and the ion of medical records. The study population for this descriptive analysis includes Registry participants who met eligibility criteria on or after December 11, 2020, the date the US Food and Drug Administration granted emergency-use authorization for the Pfizer-BioNTech vaccine. The target sample size is 1,100 pregnant women who received any dose of the Pfizer-BioNTech vaccine from 30 days prior to the last menstrual period through the end of pregnancy, and 900 comparison women who received no COVID-19 vaccine in pregnancy. Result(s): Among pregnant women participating in the Registry between 11 December 2020 and 22 July 2022, 1,100/1,100 participants (100.0% of the target sample) were enrolled as part of the Pfizer-BioNTech COVID-19 vaccine exposure cohort, and 635/900 participants (70.6% of the target sample) were enrolled in the comparator cohort. As of 22 July 2022, 858 (78.0%) in the vaccine exposure cohort and 313 (34.8%) in the comparator cohort had completed pregnancies. Descriptive data indicated numerically similar percentages of pregnancies ending in at least one liveborn infant, spontaneous abortions, stillbirths, and elective terminations across the exposed cohort stratified by trimester of the earliest dose of the Pfizer-BioNTech COVID-19 vaccine received in pregnancy, and overall in the unexposed comparator cohort. Conclusion(s): Preliminary data have not identified any new safety concerns thus far for pregnant women who receive the Pfizer-BioNTech COVID-19 vaccine during pregnancy. Funding(s): This study was conducted as a collaboration between the University of California San Diego and Pfizer. Pfizer is the study sponsor.

Beyond Symptoms Alleviation: Population-Level Benefits of COVID-19 Oral Direct-Acting Antiviral (DAA) Treatment and Resulting Decreases in Infectivity and Transmission

Objectives: Efforts to combat COVID-19 have largely focused on vaccination and non-pharmaceutical interventions to decrease hospitalization and death and to reduce transmission. First generation COVID-19 direct-acting antivirals (DAAs) are only authorized for high-risk patients to reduce individual risk of disease progression. However, DAAs can also impact transmission by reducing viral load, thereby shortening the duration of infectivity. Next generation oral DAAs in development may have safety profiles that are amenable to broader eligibility and use. This analysis estimates the economic and clinical impact of increasing the utilization of DAAs to treat COVID-19. Method(s): A susceptible-infected-recovered-susceptible model was developed to estimate COVID-19-related outcomes based on DAA uptake. Cost-savings modeled included reduced healthcare utilization amongst individual patients and, importantly, potential savings attributable to reduced transmission. Cost inputs included treatment acquisition costs, adverse events, healthcare utilization, and productivity losses based on published literature. One million individuals were assessed with clinical and economic outcomes estimated for DAA adoption by risk level. Result(s): The model projects 402,330 new infections per 1 million individuals annually, leading to 6,000 hospitalizations and 107 deaths. By increasing DAA use by 10% in the high-risk population and 20% in the standard-risk population, infections decreased to 312,000, with 1,800 fewer hospitalizations and 34 fewer deaths. Decreases in medical encounters were driven by reduction in transmission (77% of the decrease) and reduction in severity amongst those treated (23% of the decrease). Among deaths averted, 72% were attributable to the reduction in transmission. Overall, costs decrease by 23.5% with increased treatment. Conclusion(s): This study is among the first to model the potential population-level impact of DAAs in reducing infectivity and transmission, a factor currently under-emphasized in the literature. New DAAs under development with potentially improved safety profiles may expand the uptake of treatment and substantially reduce the clinical and economic burden of COVID-19.Copyright © 2023

Persons Diagnosed with COVID-19 in Linked Clinical Practice Research Datalink (CPRD) - Hospital Episode Statistics (HES) Data: A Cohort Description

Objectives: Clinical Practice Research Datalink (CPRD) Aurum captures primary care electronic healthcare records for ~28% of the population in England. From August 2020-;March 2022, all SARS-CoV-2 polymerase chain reaction (PCR) tests performed were reported back to the patient's general practitioner (GP), making the CPRD a closed system uniquely positioned to answer COVID research questions. Method(s): We defined persons with COVID as those recorded in primary care with a positive PCR test from August 1, 2020-March 31, 2021. We required continuous registration with their GP practice for >=365 days prior to diagnosis to establish comorbid conditions, and eligibility for linkage to Hospital Episode Statistics (HES) Admitted Patient Care data. Hospitalizations for COVID were defined as persons admitted with a primary diagnosis of COVID (ICD-10-CM U07.1) within 12 weeks of the initial primary care diagnosis record. Result(s): Our cohort included 535,453 persons diagnosed in primary care with COVID, with 2% later hospitalized. The hospitalized group was 57% male, 42% current/former smokers, 35% obese46% with a Charlson Comorbidity Index >1 and 98% had never received any COVID vaccine. Hospitalizations increased with age;<0.1% of patients aged 1-17, 1% aged 18-49, 4% aged 50-64, 9% aged 65-74, 13% aged 74-84, and 11% of COVID cases aged >=85 were hospitalized. Persons living in socially disadvantaged areas were overrepresented in the hospitalized cohort (25% in the Index of Multiple Deprivation's most deprived quintile). Conclusion(s): Consistent with other studies, hospitalized COVID patients were disproportionately those with male sex, smoking history, high body mass index, comorbidity and unvaccinated status. Hospitalizations were more common with age, and for individuals living in socially and economically deprived communities. Understanding the demographic and clinical characteristics of this cohort can help contextualize future work describing healthcare resource utilization and costs, as well as the impact of vaccines, associated with COVID in England.Copyright © 2023

Insurance Status Predicts Endoscopy No-Show

Introduction: Lyndon B. Johnson (LBJ) hospital is a part of the Harris Health System, which provides comprehensive care to the uninsured and underinsured population in Harris County, TX. LBJ serves a population with 55% unemployment and a median household income of $22000. Access to endoscopy is limited by resource availability, and the completion of scheduled endoscopies is essential for public health. We aimed to assess if insurance status was associated with no- show for scheduled endoscopic procedures at the LBJ GI Lab. Method(s): All patients scheduled for outpatient endoscopy during the year 2021 were collected. Included patients must have completed a GI clinic appointment, anesthesia screening, pre-procedural COVID test, confirmed attendance on pre-procedure call, and not showed for scheduled endoscopy (Figure 1). Patient's insurances statuses were: FAP (county payment assistance), Harris County Prisoners (no costs), Medicare/Medicaid (variable costs), Private Insurance (variable costs), Self-Pay, and Texas Family Planning/HCHD Presumed (temporary FAP) (Table 1). Result(s): Comparative analysis of insurance types demonstrated that patients who were Self-Pay were 5.96 times more likely (P< 0.002) not to show up for previously scheduled endoscopic procedures, while patients with the TFP/HCHD insurance were 10.1 times more likely (P< 0.001) to not show when compared to patients who were covered by the county's FAP. Conclusion(s): Our analysis demonstrated a statistically significant association between insurance status and the incidence of no-showing for endoscopy. Upon literature review, there was limited data on rates of endoscopy no-shows in relation to the out-of-pocket commitment for individuals. Further investigation into this topic would significantly affect both the academic and private practice of gastroenterologists. We plan to continue this quality assessment by meeting with the patient eligibility department to assess if modifications of benefit profiles could optimize procedural attendance.

Preparing Long-term care facilities for future pandemics-A systematic review of non-pharmacological interventions

Background Due to climate change, the likelihood of an extreme infectious disease events-similar to the COVID-19 pandemic-is very likely to increase. Anticipating and preparing for such events Is therefore essential. A setting of high risk in such an event are long-term care facilities (LTCF), which accounted for 30-60 % of all COVID-19 related deaths in most high-income countries (HIC). To prevent, mitigate, and avoid potential adverse consequences of future outbreaks of viral respiratory pathogens with pandemic potential (e.g., SARSCoV-2, SARS, MERS, influenza) in LTCFs, a systematic review will analyze which non-pharmacological interventions (NPI) are effective in LTCFs. Methods We conducted literature searches in Medline, Embase, CINAHL, and two comprehensive specialized registries focused on COVID-19-related literature. We included experimental, quasi-experimental, and specific observational studies assessing the effect of NPIs implemented in LTCFs regarding the outcomes: infections, outbreaks, hospitalizations and deaths due to the viral pathogens of interest and adverse consequences. Screening for eligibility and risk-of-bias (RoB) assessment was done in duplicate. For RoB assessment, we used the RoB2 and ROBINS-I tool. We synthesized findings narratively, focusing on the direction of effect. The certainty of evidence was evaluated using GRADE. Results We included 16 observational studies, 14 of which focused on intervention effectiveness. All were conducted in HIC and most focused on SARSCoV-2 (n = 14). There were serious concerns regarding RoB in almost all studies. We found low/very low certainty of evidence for the effectiveness of entry regulation measures (n = 1), regular testing of residents/staff (n = 5), combined outbreak control measures (n = 2), and for combinations of multiple NPIs (n = 3) in preventing outbreaks or mitigating their consequences. The evidence on the effectiveness of hand and surface hygiene interventions showed mixed results (n = 4). We found mixed results regarding adverse mental health outcomes due to visiting restrictions. Conclusion This review indicates a number of measures which could be effective in protecting residents and staff in LTCFs in upcoming extreme infectious disease epidemics, which are expected to become more likely in the future. Furthermore, we can point out several gaps in the evidence which require further research and specific study designs to improve pandemic preparedness in LTCFs.

Validity of the 2-Minute-Step Test Administered Virtually

PURPOSE/HYPOTHESIS: The 2-minute-step test (2MST) is a face-to-face (F2F) measure used to clinically evaluate aerobic capacity in adults. With the onset of the COVID-19 pandemic, the need to assess cardiovascular health in a virtual environment became evident. The 2MST is amenable to being performed in a virtual environment due to low space requirements, simple instructions, and the ability to visually count step performance through a remote visual setup. The purpose of this study is to determine if there is a difference in performance on the 2MST when administered virtually compared with F2F. NUMBER OF SUBJECTS: 28 healthy adults aged 18-35 were recruited. Subjects were screened to determine eligibility and scheduled for a practice session in both test environments. Exclusion criterion included balance impairments, cardiopulmonary conditions, and pain/recent surgeries that would adversely impact stepping performance. MATERIALS AND METHODS: Subjects performed the 2MST virtually via Zoom platform and F2F on two separate days within 1 week of each other in a counterbalanced order. The primary outcome measure was total number of steps with the right leg to the marked height in both testing sessions. Heart rate was measured prior to performance and immediately upon test completion on both days. Group differences were analyzed using twotailed paired t-tests. RESULT(S): 25 adults (mean age = 24.0 years, 9males, 16 females) completed both sessions. Three subjects were not able to complete both tests and were excluded from analysis. There is no significant difference in mean number of steps performed F2F (M=108.6, SD=11.5) and virtual (M=109.2, SD=15.1);t(24)= .359, p = .7227. The average of the difference in steps between F2F and the virtual environment was <1 step (0.6). Change in heart rate (bpm) was not significantly different in the second test (M=50.4, SD=24.8) compared with the first test (M=46.7, SD=23.6) suggesting similar exertion in both test environments;t(23)=1.0288, p= .3143. CONCLUSION(S): Our findings indicate 2MST performance in healthy adults aged 18-35 is not significantly different when administered via Zoom compared with F2F. This suggests the 2MST may be an effective tool, if a visual virtual option such as Zoom or Facetime, is available when assessing aerobic capacity remotely. Limitations of the study include generalizability to other age groups is currently unknown and the ability of subjects to independently set up the test remotely was not assessed. As in all virtual assessments, clinical reasoning guides which patients are appropriate to perform outcome measures safely, if skilled assistance in not available. CLINICAL RELEVANCE: A valid tool to assess aerobic capacity in a virtual environment can improve patient care, improve access to physical activity interventions and improve health outcomes. Vulnerable populations, such as cancer survivors, who need virtual options for ongoing care will benefit from assessment tools that are adaptable and valid in virtual settings.

Striking a match between FHIR-based patient data and FHIR-based eligibility criteria

Inputs and Outputs: The Strike-a-Match Function, written in JavaScript version ES6+, accepts the input of two datasets (one dataset defining eligibility criteria for research studies or clinical decision support, and one dataset defining characteristics for an individual patient). It returns an output signaling whether the patient characteristics are a match for the eligibility criteria.Purpose: Ultimately, such a system will play a "matchmaker" role in facilitating point of-care recognition of patient-specific clinical decision support.Specifications: The eligibility criteria are defined in HL7 FHIR (version R5) Evidence Variable Resource JSON structure. The patient characteristics are provided in an FHIR Bundle Resource JSON including one Patient Resource and one or more Observation and Condition Resources which could be obtained from the patient's electronic health record.Application: The Strike-a-Match Function determines whether or not the patient is a match to the eligibility criteria and an Eligibility Criteria Matching Software Demonstration interface provides a human-readable display of matching results by criteria for the clinician or patient to consider. This is the first software application, serving as proof of principle, that compares patient characteristics and eligibility criteria with all data exchanged using HL7 FHIR JSON. An Eligibility Criteria Matching Software Library at https://fevir.net/110192 provides a method for sharing functions using the same information model.

Utilizing a Decentralized Clinical Study Approach for Expedited and Diverse Recruitment for Clinical Validation of a Novel Non-invasive Multitargeted Stool-based RNA Test

Introduction: Traditional clinical trials that utilize fixed sites often fail to recruit participants that are representative of the intended use population. Participants, particularly those from minority groups, cite geographical constraints, mistrust, miscommunication, and discrimination as barriers to successful recruitment. A decentralized clinical trial enrollment strategy offers reduced cost, reduced time requirements, and circumvents barriers associated with the recent pandemic outbreak. Method(s): After the mt-sRNA test system entered design-lock, a decentralized clinical trial (CRC-PREVENT) was launched through a digital campaign (https://www.colonscreeningstudy.com/;NCT04739722). Online advertisements were published on multiple social media sites, and engagement with materials directed patients to an online screener. Participants who completed the screener were eligible for enrollment if they met CRC-PREVENT inclusion and exclusion criteria and were willing to complete all clinical trial components, including providing a stool sample before an optical colonoscopy. Result(s): After 12 months of active enrollment, 276,400 individuals engaged with digital advertisements and completed pre-screener surveys to determine eligibility for the clinical trial. In total, 14,264 individuals consented to participate in the CRC-PREVENT clinical trial. Of these individuals, 58% were female (42% were male), and 65% were over 50. Regarding race and ethnicity, eligible individuals directly represented the intended use population: 16% were Black or African American, 0.2% were Native Hawaiian, Pacific Islander, American Indian, or Alaskan Native, and 7% were Hispanic or Latinx. Regarding socioeconomic status, the decentralized approach permitted access to individuals with healthcare inequities: 25% of participants had income under $29,999, 5% of participants were from rural areas (defined as a city center , 10,000 people), and 36.7% of participants were on public insurance. Individuals were derived from 7,644 unique zip codes across all 48 continental United States. (Table) Conclusion(s): A decentralized recruitment strategy permits highly successful enrollment in the face of screening burdens heightened by COVID-19 pandemic. This approach also offered a significantly more diverse population and could mitigate selection bias and attrition bias associated with the cohorts observed in traditional clinical studies.