Validation of the russian version of the 4C Mortality Score and prediction of outcomes of severe COVID-19

The aim of the study is to validate the Russian version of the 4C Mortality Score scale and evaluate its accuracy in predicting the outcomes of severe COVID-19. Material and methods. The staff of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology received official permission from the authors to conduct a validation study of the 4C Mortality Score scale in Russia. In the course of the work, the linguistic and cultural ratification of the scale was carried out and its Russian-language version was prepared. Psychometric properties (reliability and validity) The Russian-language version was evaluated on a group of 78 patients (37 of whom were men, aged 34 to 88 years) with a confirmed diagnosis of COVID-19, hospitalized in the City Clinical Hospital No. 15 named after O.M. Filatov (Moscow) in the period from June to August 2021. Results. The linguocultural adaptation of the 4C Mortality Score scale was successfully carried out. High levels of reliability were obtained (Spearman correlation coefficient rho=0.91, p<0.0001;Cronbach's alpha alpha=0.73, p=0.0002;Cohen's kappa kappa=0.85, p<0.0001). It is shown that the 4C Mortality Score scores have a significant correlation with the COVID-GRAM scores (r=0.72, p=0.002) and NEWS2 (r=0.54, p=0.004). Conclusion. As a result of the validation study, the official Russian version of the 4C Mortality Score scale was developed. It is recommended for use by medical professionals of various specialties at all stages of providing medical care to patients with COVID-19. The scale is available for download on the website of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology (https://www.neurology.ru/reabilitaciya/centr-validacii-mezhdunarodnyh-shkal-i-oprosnikov).Copyright © 2022 by the authors.

Hypofractionated radiotherapy for pancreatic cancer

Category: Outcomes of treatment (including chemotherapy, chemo-RT and RT) Purpose: Hypofractionated (5#) radiotherapy for non-metastatic pancreatic cancer was introduced during the COVID-19 pandemic as an alternative to conventional treatment pathways. This study was performed to evaluate clinical outcomes and acute toxicity of 5# radiotherapy. Methods and materials: We retrospectively identified pancreatic cancer patients treated with 5# radiotherapy at Addenbrookes Hospital from March 2020 to September 2021. Patient characteristics, response on follow-up computed tomography (CT) scans, dosimetry and toxicity data were analysed using Excel and SPSS. Result(s): 40 patients were treated with 5# radiotherapy, 60% (n=24) had locally advanced pancreatic cancer, 30% (n=12) operable disease, 7.5% (n=3) postoperative recurrences and 2.5% (n=1) borderline resectable disease. 45% of patients (n=19) had induction chemotherapy. Radiotherapy was delivered as 35 Gy (67.5%, n= 27) and 30 Gy (32.5%, n=13) in 5# in 1.5 weeks using volumetric-modulated arc therapy (VMAT) technique. Median overall survival (mOS) for all patients was 14.2 months (95% CI 10.3-15.6 months). For induction chemotherapy + radiotherapy versus radiotherapy alone, mOS was 14.2 months (95% CI 8.2-17.7 months) versus 13.9 months (95% CI 10.3-15.7 months), p=0.97. Median progression-free survival (mPFS) for all patients was 10.2 months (95% CI 8.0-11.9 months). For induction chemotherapy + radiotherapy versus radiotherapy alone, mPFS was 10.5 months (95% CI 9.5-12.4 months) versus 10.1 months (95% CI 5.5-10.4 months), p=0.99. There were no grade 3 acute toxicities. When compared to 28# radiotherapy, the 5# regimen reduced patient hospital visits by 82%. Conclusion(s): The observed mOS is comparable with mOS of conventional 28# radiotherapy (14.2 versus 15.2 months (SCALOP trial)), 5# radiotherapy for non-metastatic pancreatic cancer is a safe alternative treatment pathway. Copyright © 2022

Validation of the russian version of the 4C Mortality Score and prediction of outcomes of severe COVID-19

The aim of the study is to validate the Russian version of the 4C Mortality Score scale and evaluate its accuracy in predicting the outcomes of severe COVID-19. Material and methods. The staff of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology received official permission from the authors to conduct a validation study of the 4C Mortality Score scale in Russia. In the course of the work, the linguistic and cultural ratification of the scale was carried out and its Russian-language version was prepared. Psychometric properties (reliability and validity) The Russian-language version was evaluated on a group of 78 patients (37 of whom were men, aged 34 to 88 years) with a confirmed diagnosis of COVID-19, hospitalized in the City Clinical Hospital No. 15 named after O.M. Filatov (Moscow) in the period from June to August 2021. Results. The linguocultural adaptation of the 4C Mortality Score scale was successfully carried out. High levels of reliability were obtained (Spearman correlation coefficient ρ=0.91, p<0.0001;Cronbach's alpha α=0.73, p=0.0002;Cohen's kappa κ=0.85, p<0.0001). It is shown that the 4C Mortality Score scores have a significant correlation with the COVID-GRAM scores (r=0.72, p=0.002) and NEWS2 (r=0.54, p=0.004). Conclusion. As a result of the validation study, the official Russian version of the 4C Mortality Score scale was developed. It is recommended for use by medical professionals of various specialties at all stages of providing medical care to patients with COVID-19. The scale is available for download on the website of the Center for Validation of International Scales and Questionnaires of the Research Center of Neurology (https://www.neurology.ru/reabilitaciya/centr-validacii-mezhdunarodnyh-shkal-i-oprosnikov). © 2022 by the authors.

The evolving attitude towards privacy and security of personal genomic data

Introduction: Usage of genomic testing, including multi-gene panel, genomic sequencing (GS) and Direct-to-Consumer testing, continues to grow in both medical settings and for personal use. Much has been written about the concerns prospective users of genomic testing have had about the privacy and security of their genomic test results. Predominate concerns reported include that genomic information could be used by insurance companies to deny insurance or raise premiums beyond their ability to afford it, employment discrimination and the use of genomic data without consent. As a result of society’s growing familiarity with genomic testing, individual considerations of benefits and risks of having their genomic data stored in secure databases may be shifting from what had been previously reported. Our study aim was to identify current views about security and privacy of genomic testing and to describe how security and privacy considerations are weighed compared to health benefits among Veterans who receive their healthcare in the VA. Methods: We conducted 14 90-minute focus groups with Veterans located in Salt Lake City, Durham, and Boston. To be eligible, Veterans had to be enrolled in VA health care and have received health care in the year they were recruited. A convenience sample was recruited using a variety of methods including by being approached by study personnel in a VA health center waiting room or area near nearby and flyers posted on bulletin boards in VA health center hallways. Most of the focus group included approximately 5 to 8 participants to ensure adequate size to represent a range of experiences with and perceptions of genomics and sufficient time for each participant to contribute to the discussion. The Boston and Durham each conducted 4 in-person focus groups between November 2017 and April 2018. The Salt Lake City conducted 6 focus groups, remotely, due to COVID-19 restrictions, using HIPAA compliant Zoom. All participants for Boston and Durham in person were consented in-person. Salt Lake City participants received a copy of the consent form by either an encrypted email or by post to review ahead of a Zoom technology orientation session when the consent process was completed. Experienced moderators (BL, NS, SJK) conducted the focus groups with trained staff members assisting, using a structured guide. The guide was iteratively developed to incorporate novel topics for discussion in subsequent focus groups. Participants were asked open-ended questions about their understanding of genomics, use of genomics to assess health risk, diagnose and treat disease, opinions, and concerns about genetic testing and specifically GS, and understanding and expectations of genomic healthcare services including who should be providing these services. Focus groups were audio recorded, transcribed, de-identified, and deductively coded independently in ATLAS.ti (version 8.4, 2017;ATLAS.ti GmbH) using a content analysis approach by two of the authors (BL, DGP). Discrepancies in coding, which primarily concerned categorization of secondary-level codes and the amount of text selected as part of the coded text, were discussed and resolved via consensus between the two coders and the project principal investigator (SJK). All data coded as being related to security and privacy of genomic information were further analyzed and sub-themes were identified to address the more nuanced concerns expressed by the Veterans. Results: A total of 60 Veterans participated in the focus groups. Twelve were female;48 were male. Thirty of the participants reported themselves to be White, 21 as Black or African American, 4 as more than one race and 5 did not report a race category. All participants expressed some level of concern about the privacy and security of their genomic information, should they be tested;however, participants indicated that the benefits they and their families could derive from GS outweighed the risk to their privacy and were still willing to have GS, if appropriate. Some articulated worries about society cre ting classes of people based on genomic risks identified through GS. They felt it could lead to discrimination, especially by insurance companies and employers regardless of the current laws to protect against it. There was a great deal of mistrust of corporations doing the “right thing” because of the pressure to maximize profits. They were also concerned that the military would use the genomic information to determine whether they would be allowed to join. Participants expressed skepticism about the ability to protect any kind of medical data, and some felt resigned that there is no real privacy anymore. They noted that Veterans have experienced situations in which a hospital employee mistakenly released their medical data to the wrong recipient and believe there is almost no perfect way to prevent a security breach if someone wants to access databases for nefarious reasons. One participant voiced their apprehension about how this lack of data could lead to an unwillingness of individuals to participate in research, thus limiting new medical discoveries. While participants raised concerns, they described feeling that the VA is doing a good job of protecting their medical data and they identified benefits that to them would outweigh risks. Specifically, they discussed that the ability to prevent disease onset, manage a diagnosed disease, and provide predisposition information for family members, especially offspring, would outweigh any possible negative outcomes from privacy loss. Conclusion: While Veterans continue to express concerns about the security and privacy of their genomic data, there appears to be a relaxing of those worries, accepting that protecting data from those wanting to use it for nefarious reasons is extremely difficult and that the benefits the Veterans can derive from the genomic testing outweighs their concerns.

Acute-phase bed-rest duration was associated with lower grip strength in a post-covid-19 cohort

Background: Though age-related muscle loss is traditionally associated with older cohorts, strong evidence suggests a life-spanning precipitation of decreasing muscle mass and strength beginning as early as the fourth decade of life, with established deleterious consequences for later-life morbidity and mortality. Periods of low activity and bed rest (LA/BR) can further compound this depletion of muscle strength. Our aim was to examine such associations in a post-COVID-19 cohort. Methods: Participants reporting ongoing symptomatology and fatigue post COVID-19 underwent assessments of grip strength via hand-held dynamometry (2 measures on each hand). Demographics of COVID-19 illness, including time since diagnosis, duration of LA/BR during acute illness, and levels of fatigue were captured via self-reported questionnaires. Independent predictors of mean grip strength were investigated using a linear regression model. Results: Forty-nine participants underwent assessments (69% female, mean age 44(12) years). At the time of assessment, days post COVID-19 diagnosis ranged from 39-522 (mean 262(140)). The mean self-reported period of LA/BR during the acute illness was 15(18) days. In general, participants reported significant levels of fatigue (median Chalder Fatigue Scale score 22(8)). Mean grip strength was 41.3(6.3) Kg for men and 22.8(6.7) Kg for women. When predictors of grip strength were investigated, an increased duration of LA/BR was found to be associated with lower grip strength, independently of age, gender, time since COVID-19 diagnosis, and self-reported fatigue (Beta=-0.158, 95% Confidence Interval-0.242 to -0.074, p=0.001). Conclusion: In this cohort, every day of LA/BR during acute COVID-19 illness was independently associated with subsequent lower grip strength of approximately 150 g. These results underscore the importance of early mobilization and discouraging bed rest in the acute phase of COVID-19. Patients who are isolating should be encouraged to maintain physical activity and muscle strength as part of a modified isolation-friendly rehabilitation programme.

Impact of the covid pandemic on depression and subsequent emergency department visits for anxiety and chest pain

Background: The COVID-19 pandemic has affected nearly every aspect of daily life. The interpersonal loss due to quarantining and social distancing, compounded with societal disruption has negatively affected mental health. Once established, mental health conditions can become chronic with having subsequent effects on additional risk factors and disease incidence, such as cardiovascular disease (CVD). Methods: Patients who completed a PHQ-9 in a primary care setting in the year prior to the COVID pandemic (Mar 1, 2019 to Feb 29, 2020) and during the COVID pandemic (Mar 1, 2020 to Apr 20, 2021) were studied. Patients were stratified into 2 groups: no depression/no longer depressed and remained depressed/became depressed. Patients were assessed for follow-up emergency department (ED) visits for anxiety and chest pain (CP) after PHQ-9 completion during the pandemic. Results: A total of 4,633 patients were studied, with 2,848 (61.5%) being never/no longer depressed and 1,785 (38.5%) remaining/became depressed. PHQ-9 scores during the pandemic were higher than prior to the pandemic among those depressed. A total of 2,171 (46.6%) received a COVID test, with more depressed patients tested compared to non-depressed (Table), but with positivity for SARS-CoV-2 (n=362 [16.7%]) being similar (p=0.18). The table shows baseline characteristics and outcomes. Depression was associated with increased ED visits for anxiety (Table). Those with depression, visited the ED at 3.5 times and 2.7 times greater rate for anxiety and anxiety with CP compared to non-depressed, respectively. Conclusions: Depression was highly prevalent among patients who receive routine primary care, with depressive symptoms increasing during the pandemic. Since depression and anxiety are associated with an increased risk of CVD and associated risk factors, identifying and treating patients early who exhibit such symptoms will be important in reducing the risk of future CVD and risk factor incidence.

A small but significant increased incidence of acute pericarditis identified after vaccination for sarscov-2

Background: As SARS-CoV-2 vaccines are being administered on an unprecedented scale, it is critical to carefully assess risks to aid clinicians in the early detection and treatment of potential side effects. Here we examine increases in the risk of pericarditis following SARS-CoV-2 vaccination. Methods: We examined pericarditis cases from December 15, 2020, to April 15, 2021 seen within Intermountain Healthcare, an integrated healthcare system. Pericarditis was defined by at least two of the following criteria: chest pain, EKG changes, pericardial effusion, and pericardial rub;excluded cases secondary to non-infectious causes (e.g., AF ablation). We determined vaccination within 60 days prior to pericarditis diagnosis using Intermountain and Utah Department of Health vaccination information. Rates of pericarditis per 10 million patient days for vaccinated patients compared to unvaccinated patients were compared. We also examined a case-crossover design with 4 control dates for each pericarditis case. Results: Of the 29 identified pericarditis cases, 13 (44.8%) had a SARS-Cov-2 vaccination within 60 days before the onset of pericarditis. During the same period, 743,774 individuals in the Intermountain Healthcare system had received at least one dose of the SARS-CoV-2 vaccine. Thus, 1.7 per 100,000 vaccinated individuals were diagnosed with acute pericarditis. Within a 60-day postvaccination window, the rate of acute pericarditis per 10-million patient-days was 3.90 in the vaccinated group and 0.84 in the unvaccinated group. Thus, there was a 4.49 times higher rate of acute pericarditis in vaccinated patients compared to the unvaccinated individuals (p=0.0002). Case-crossover analysis showed the odds of acute pericarditis was 3.33 higher (95% CI: 1.29, 10.14) in the vaccinated versus the unvaccinated group (p=0.01). Conclusions: We found acute pericarditis to be a rare post-SARS-CoV-2 vaccination event, but the risk was significantly higher than in comparable unvaccinated subjects. This risk of pericarditis postSARS-CoV-2 vaccine is eclipsed by the risk of contracting COVID-19 and its associated, commonly seen severe outcomes. Nevertheless, clinicians should be informed of this risk to facilitate earlier recognition and treatment.

Sars-cov-2 b.1.1.7 variants do not increase risk of subsequent cardiovascular disease

Background: The SARS-CoV-2 B.1.1.7 variant, also known as the UK or alpha variant, carries the spike 69/70 deletion mutation and has been reported to be more contagious and possibly more virulent than other variants. This study examines follow-up cardiovascular outcomes for patients infected with deletion-carrying SARS-CoV-2 alpha variant. Methods: From October 2020 to May 2021, all positive SARS-CoV-2 samples at Intermountain Healthcare were tested for the 69/70 deletion (n=92822). Patient characteristics, COVID-19 treatments, and follow-up outcomes were extracted from Intermountain records. Cox hazard regression analysis with multivariable adjustment was used to determine risk of subsequent major cardiovascular adverse event outcomes (MACE), which included all-cause death, heart failure (HF), and hospitalization for coronary artery disease (CAD) or atrial fibrillation (AF). Results: Overall, 4.2% of patients testing positive for the SARS-CoV-2 virus carried the deletion mutation with prevalence increasing with time, ranging from 1.3% in October to 61.0% in May. Baseline characteristics, treatments, and outcomes stratified by non-mutant and deletion mutation status are shown in the Table. While the mutation did result in higher rates of COVID hospitalization (adjusted OR=1.68, p<0.001), there was no difference in overall MACE after adjustment by baselinecharacteristics and risk factors. There was a non-significant trend toward an increased rate of allcause death in patients carrying the mutant variant (adjusted HR=1.90, p=0.12). Conclusions: The SARS-CoV-2 deletion mutant, while resulting in an increased risk of COVID hospitalization and a trend toward increased death, did not increase the risk of subsequent CVD. Because of the recent emergence of the variant the long-term effects are not known. Thus, it remains important to minimize risk of exposure. Moreover, long-term surveillance of subsequent CVD risk is warranted.

Atrial fibrillation is a cardiovascular risk factor for worse prognosis in covid-19

Background: In the presence of comorbid conditions, COVID-19 infections are known to require more advanced treatment, poorer outcomes and have longer-term sequelae. New-onset atrial fibrillation (AF) during COVID-19 infection has been associated with worse cardiovascular outcomes but not mortality. However, it remains unclear whether a prior history (hx) of atrial fibrillation is a cardiovascular risk factor predicting a worse outcome in COVID-19 patients. As such, we examined, using propensity matching accounting for possible confounders, the need for advanced treatment and subsequent major cardiovascular events (MACE) in patients with a prior hx of AF with COVID19 infection. Methods: From March 2020 to May 2021, patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n=3119) were propensity matched for age, gender, race/ethnicity, prior coronary artery disease (CAD), prior heart failure (HF), prior stroke and hypertension to non-AF SARS-CoV-2 positive patients. Cox hazard regression analysis with multivariable adjustment was used to determine risk of subsequent MACE (all-cause death, myocardial infarction, HF and stroke). Results: Baseline characteristics, treatments, and outcomes stratified by AF status are shown in the Table. While the groups had similar baseline characteristics, AF COVID-19 patients were more likely to require hospitalization, ICU care, and ventilator support. Consistent with our hypothesis, composite MACE event rates were higher in the AF patients (HR=1.60, p<0.0001) secondary to increases in heart failure and all-cause mortality rates. Conclusions: These data support AF as a cardiovascular risk factor predicting worse outcomes in COVID-19 patients. Specifically, AF increases the need for advanced treatments such as hospitalization, ICU care and ventilator support resulting in an increase in subsequent heart failure and all-cause mortality.

Persistence of neutrophil abnormalities inCOVID-19 convalescence

Background/AimsPatients infected with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) may develop acute respiratory inflammation, due toan exaggerated immune response and some develop chroniccomplications. Neutrophils play a major role in the pathology ofinflammatory diseases and have been shown to contribute to lung andvascular damage in COVID-19. Our aim was to establish a relationshipbetween neutrophil phenotype and disease severity and to determinewhether neutrophil abnormalities persist in convalescent patients.MethodsPeripheral blood samples were obtained from acute COVID-19patients (n = 74), follow-up (FU) patients discharged following inpatientadmission (n = 56), a median of 87 days after discharge, and healthycontrols (HCs, n = 22). Patients were stratified by disease severitybased on inspired oxygen (FiO2) and admission to intensive care (ICU).Neutrophils were isolated from whole blood by negative selection forphenotyping and functional analysis. PBMC Isolation Tubes were usedto quantify and phenotype low density neutrophils (LDNs) within thePBMC fraction. For quantification of reactive oxygen species (ROS)production, isolated neutrophils were incubated with a ROS reactivedye, DHR-123 and stimulated with PMA. All samples were stained andfixed prior to analysis by flow cytometry.ResultsThere was a marked increase in neutrophils expressing the activationand degranulation markers, CD64 (P < 0.0001) and CD63 (P < 0.0001)and a reduction in neutrophils expressing the maturity markers, CD10(P < 0.0005) and CD101 (P < 0.0005) in patients with acute COVID-19compared to HCs. Increased frequency of neutrophils expressingCD64 (P < 0.005), CD63 (P < 0.01) and expressing decreased CD101(P < 0.0001) were also detected in FU patients compared to HCs.Notably, 42.3 4.4% of neutrophils were CD101lo in FU patients, compared to 29.0 3.7% in acute patients and 9.6 4.1% in HCs.These changes were most apparent in FU patients recovering fromsevere COVID-19 compared to mild or moderate disease. Thefrequency of LDNs in PBMCs from acute patients was significantlyhigher than HCs (P < 0.0001), and correlated with disease severity.Similarly, the frequency of LDNs in FU patients was significantly higherthan in HCs (P < 0.0005). We found a trend towards higher basal ROSproduction in acute and FU patients, but a blunted response to PMAstimulated ROS production in neutrophils from acute patients versusHCs (P < 0.0001). Impaired ROS production persisted in FU patientscompared to HCs (P < 0.01).ConclusionCirculating neutrophils in acute COVID-19 have an altered phenotypeand comprise immature and activated cells. This altered phenotypepersisted in convalescence and may contribute to the persistence ofsymptoms and an increased susceptibility to subsequent infections.Future work will aim to investigate the functional implications of thesefindings.

A critical race theory curriculum for emergency medicine learners

Intro/Background: The death of George Floyd in May 2020 led to increased awareness of longstanding racism and anti-Blackness in the US. In this setting, various medical institutions have released statements condemning racism and injustice in medicine. Critical race theory provides a race-conscious framework with which to examine inequity, power, and justice. CRT has been incorporated into law, political science, sociology, and other fields but, thus far, medicine has failed to formally embrace its teachings. Purpose/Objective: We set out to develop and carry out a Critical Race Theory curriculum to address an identified gap in emergency medicine education. Sessions explored concepts of critical race theory and issues of racism as they relate to the clinical and extraclinical environments. Methods: We developed a series of five virtual workshop sessions in 2019 which were held over Zoom in June and July 2020 in the setting of the 2020 COVID-19 pandemic. Eight learners completed the curriculum. All sessions were facilitated by the creators of this curriculum, both facilitators have experience guiding workshop discussions related to topics of race. Sessions were held weekly for between 90 to 120 minutes. Outcomes (if available): Surveys identified increased comfort discussing topics of racism, sustained motivation, and increased familiarity with Critical Race Theory among participants. Learners were also more likely to report having a framework for approaching topics of race and racism which is critical for engaging with these and other topics in the future. Summary: We set out to develop and carry out a Critical Race Theory curriculum to address an identified gap in emergency medicine education. Sessions explored concepts of critical race theory and issues of racism as they relate to the clinical and extraclinical environments. We developed a series of five virtual workshop sessions in 2019 which were held over Zoom in June and July 2020 in the setting of the 2020 COVID-19 pandemic and were facilitated by the creators of the curriculum. Fifteen incoming emergency medicine interns at the University of California-San Francisco were invited to participate in the curriculum on a voluntary basis. Nine learners showed interest in the curriculum and opted-in to participation. Ultimately, eight learners completed the curriculum. Prior to each session, learners were provided pre-session materials including podcasts, recorded lectures, and readings. Pre-session materials did not exceed 2 hours of work. Thought questions were also provided with pre-session materials to facilitate discussion during sessions. Materials were curated to provide foundational knowledge on Critical Race Theory and US history as well as relate to local history in San Francisco and the Bay Area. Participants universally found our Critical Race Theory curriculum useful and reported increased comfort discussing topics of racism, sustained motivation, and increased familiarity with Critical Race Theory. Opt-in participation contributed to a very engaged cohort of learners and the small group size encouraged participation by all learners. The virtual format made attendance less burdensome for participants. Semi-structured facilitation allowed participants to guide conversations to their own topics of interest while also addressing specific topics at hand. Independent, guided pre-work allowed participants to gather knowledge at their own pace prior to each session which likely contributed to more full participation.