Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs. (preprint)

IntroductionCOVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. MethodsThis retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. Results10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). ConclusionsFindings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.

Effectiveness of COVID-19 Treatment With Nirmatrelvir-Ritonavir or Molnupiravir Among U.S. Veterans: Target Trial Emulation Studies With One-Month and Six-Month Outcomes.

BACKGROUND: Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited. OBJECTIVE: To measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19. DESIGN: Three retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir. SETTING: Veterans Health Administration (VHA). PARTICIPANTS: Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022. INTERVENTION: Nirmatrelvir-ritonavir or molnupiravir pharmacotherapy. MEASUREMENTS: Incidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days. RESULTS: Eighty-seven percent of participants were male; the median age was 66 years, and 18% were unvaccinated. Compared with matched untreated control participants, those treated with nirmatrelvir-ritonavir (n = 9607) had lower 30-day risk for hospitalization (22.07 vs. 30.32 per 1000 participants; risk difference [RD], -8.25 [95% CI, -12.27 to -4.23] per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22 [CI, -5.45 to -3.00] per 1000 participants). Among persons alive at day 31, reductions were seen in 31- to 180-day incidence of death (hazard ratio, 0.66 [CI, 0.49 to 0.89]) but not hospitalization (subhazard ratio, 0.90 [CI, 0.79 to 1.02]). Molnupiravir-treated participants (n = 3504) had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42 [CI, -13.49 to -7.35] per 1000 participants; hazard ratio at 31 to 180 days, 0.67 [CI, 0.48 to 0.95]) but not hospitalization. A difference in 30-day or 31- to 180-day risk for hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. LIMITATION: The date of COVID-19 symptom onset for most veterans was unknown. CONCLUSION: Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not hospitalization. Further reductions in mortality from 31 to 180 days were observed with both antivirals. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Yikes! The Effect of Incidental Disgust and Information on Public Attitudes During the COVID-19 Pandemic.

Existing research has focused extensively on the role of emotions such as anger, fear, and enthusiasm in explaining public opinion, but less is known about the importance of disgust, an innate disease-related emotion. To study the independent and joint effects of disgust and information, I draw on the case of the COVID-19 pandemic. I demonstrate that experimentally induced incidental disgust and exposure to information about how to flatten the curve of the COVID-19 cases have distinctive effects on political, racial, and health attitudes. Independently, exposure to information affects preferences only for restrictive policies to fight the spread of the virus. In contrast, the stand-alone effect of incidental disgust, as well as its joint effect with exposure to information, are responsible for attitude change toward both pandemic-relevant and irrelevant policies, Asian minorities, and prevention measures. Importantly, the study finds that citizens respond symmetrically to disgusting stimuli and information across degrees of political awareness, ideology, partisan affiliation, and trait authoritarianism. The results draw attention to the far-reaching implications of disgust on public opinion under threatening conditions.

Adverse outcomes of SARS-CoV-2 infection with delta and omicron variants in vaccinated versus unvaccinated US veterans: retrospective cohort study.

OBJECTIVES: To determine the association between covid-19 vaccination types and doses with adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the periods of delta (B.1.617.2) and omicron (B.1.1.529) variant predominance. DESIGN: Retrospective cohort. SETTING: US Veterans Affairs healthcare system. PARTICIPANTS: Adults (≥18 years) who are affiliated to Veterans Affairs with a first documented SARS-CoV-2 infection during the periods of delta (1 July-30 November 2021) or omicron (1 January-30 June 2022) variant predominance. The combined cohorts had a mean age of 59.4 (standard deviation 16.3) and 87% were male. INTERVENTIONS: Covid-19 vaccination with mRNA vaccines (BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)) and adenovirus vector vaccine (Ad26.COV2.S (Janssen/Johnson & Johnson)). MAIN OUTCOME MEASURES: Stay in hospital, intensive care unit admission, use of ventilation, and mortality measured 30 days after a positive test result for SARS-CoV-2. RESULTS: In the delta period, 95 336 patients had infections with 47.6% having at least one vaccine dose, compared with 184 653 patients in the omicron period, with 72.6% vaccinated. After adjustment for patient demographic and clinical characteristics, in the delta period, two doses of the mRNA vaccines were associated with lower odds of hospital admission (adjusted odds ratio 0.41 (95% confidence interval 0.39 to 0.43)), intensive care unit admission (0.33 (0.31 to 0.36)), ventilation (0.27 (0.24 to 0.30)), and death (0.21 (0.19 to 0.23)), compared with no vaccination. In the omicron period, receipt of two mRNA doses were associated with lower odds of hospital admission (0.60 (0.57 to 0.63)), intensive care unit admission (0.57 (0.53 to 0.62)), ventilation (0.59 (0.51 to 0.67)), and death (0.43 (0.39 to 0.48)). Additionally, a third mRNA dose was associated with lower odds of all outcomes compared with two doses: hospital admission (0.65 (0.63 to 0.69)), intensive care unit admission (0.65 (0.59 to 0.70)), ventilation (0.70 (0.61 to 0.80)), and death (0.51 (0.46 to 0.57)). The Ad26.COV2.S vaccination was associated with better outcomes relative to no vaccination, but higher odds of hospital stay and intensive care unit admission than with two mRNA doses. BNT162b2 was generally associated with worse outcomes than mRNA-1273 (adjusted odds ratios between 0.97 and 1.42). CONCLUSIONS: In veterans with recent healthcare use and high occurrence of multimorbidity, vaccination was robustly associated with lower odds of 30 day morbidity and mortality compared with no vaccination among patients infected with covid-19. The vaccination type and number of doses had a significant association with outcomes.

MENTAL HEALTH PROMOTION: PERSON-CENTERED PERSPECTIVE

Background: Having the person at the center of health, both in person-centered clinical care and people-centered public health [1] are a guiding principle in health promotion. Mental health is an integral part of each person's health and well-being. This is an absolute necessity always and more so during the years of the coronavirus pandemic and the post-pandemic "new normal”. Objective: To discuss the basic concepts of health, mental health, health promotion and mental health promotion, focusing on peace and justice, two key target areas and goals of mental health promotion [2,3]. Method: The holistic approach, the need to reduce stigma and discrimination, and the person- and people-centered approach in mental health promotion were reviewed. Results: The importance of identifying target populations and using paradigms of mental health promotion initiatives, like the Athens Mental Health Promotion Initiative, was noted, as well as the positive role played by celebrities who have excelled despite their mental disorders ("recovery”). The relevance of mental health promotion guidance and effectiveness of existing mental health promotion strategies have to be updated by further research in order to meet the need for intensification of mental health promotion efforts during the COVID pandemic. Conclusion: In the post-COVID era a "new normal” requires an update of policies for an intensified and different person-centered approach delivered by different providers to different recipients of services.

Acceptability and perception of COVID-19 vaccines among foreign medical students in China: A cross-sectional study.

Background: Acceptability and perception of the COVID-19 vaccine among different social groups have been the subject of several studies. However, little is known about foreign medical students in Chinese universities. Aim: This study, therefore, fills the literature gap using a focus group technique to assess the acceptance and perception of the COVID-19 vaccine among foreign medical students in China. Methods: The study adopted an online cross-sectional survey method following the Chinese universities' lockdowns to collect the data between March and April 2022. A data collection questionnaire was developed, and then the link was shared with the respondents through key informants in different universities in China to obtain the data. The data collection process only included foreign medical students who were in China from May 2021 to April 2022. The authors received a total of 403 responses from the respondents. During data processing, we excluded 17 respondents since they were not in China while administering the questionnaire to enhance the data validity. The authors then coded the remaining 386 respondents for the estimation process. We finally applied the multilinear logistics regression technique to model the COVID-19 vaccine acceptance with the response or influencing factors, including the mediating factors among the foreign medical students in China. Results: The data statistics show that 4.9% of the respondents were younger than 20 years, 91.5% were 20-40 years old, and 3.6% were older than 40 years; 36.3% of respondents were female subjects and 63.7% were male subjects. The results also show that the respondents are from six continents, including the African continent, 72.4%, Asia 17.4%, 3.1% from Europe, 2.8% from North America, 1.6% from Australia, and 2.3% from South America. The mediation analysis for the gender variable (ß = 0.235, p = 0.002) suggests that gender is a significant channel in COVID-19 vaccine acceptance and perception among foreign medical students in China. Also, the main analysis shows that opinion on the safety of the vaccine (ß = 0.081, p = 0.043), doses of the vaccine to receive (ß = 0.175, p = 0.001), vaccine safety with some side effects (ß = 0.15, p = 0.000), and the possibility of acquiring COVID-19 after vaccination (ß = 0.062, p = 0.040) are all positive factors influencing vaccine acceptability and perception. Also, the home continent (ß = -0.062, p = 0.071) is a negative factor influencing COVID-19 vaccine acceptance and perception. Furthermore, the finding shows that fear perceptions has affected 200 (51.81%) respondents. The medical students feared that the vaccines might result in future implications such as infertility, impotence, and systemic health conditions such as cardiovascular, respiratory, or deep vein thrombosis. In addition, 186 (48.19%) students feared that the vaccines were intended to shorten life expectancy. Conclusion: COVID-19 vaccination acceptability and perception among medical students in China is high, most predominantly due to their knowledge of medicine composition formulation. Despite widespread acceptance by the general public and private stakeholders, we concluded that vaccination resistance remains a significant factor among medical students and trainees. The study further adds that in considering the COVID-19 vaccine, the factor of the home continent plays a significant role in vaccine hesitancy among foreign medical students. Also, knowledge, information, and education are important pillars confronting new medicine administered among medical trainees. Finally, there is a low rate of COVID-19 vaccine hesitancy among foreign medical students in China. The study, therefore, recommends targeted policy strategies, including sensitization, detailed public information, and education, especially for medical colleges and institutions on the COVID-19 vaccination, to achieve 100%. Furthermore, the study recommends that future researchers explore other factors influencing accurate information and education for successful COVID-19 vaccination implementation.

Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023 (preprint)

IMPORTANCESeveral pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed. OBJECTIVETo analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA). DESIGN, SETTINGS, AND PARTICIPANTSThis cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases. EXPOSURESDemographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination. MAIN OUTCOMES AND MEASURESMonthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy. RESULTSAmong 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI [≥]6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment. CONCLUSIONS AND RELEVANCEAmong veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.

Perception of competence achievement and students' satisfaction using virtual laboratories in Medical Biochemistry course: Lessons from the COVID-19 pandemic.

After the COVID-19 pandemic, there was an increasing demand for remote learning and an expansion in the substitution of traditional practical sessions with lab-based virtual tools. This study aimed to assess the effectiveness of virtual labs in practicing biochemical experiments and to examine the student's feedback regarding this tool. Virtual and traditional labs training were compared in teaching qualitative analysis of proteins and carbohydrates experiments for first-year medical students. Students' achievements were assessed, and their satisfaction regarding virtual labs was estimated using a questionnaire. A total of 633 students were enrolled in the study. There was a significant increase in the average scores of students performing the virtual lab of protein analysis compared with those trained in a real lab and those who watched videos explaining the experiment (p < 0.001). The opposite was noticed in the qualitative analysis of carbohydrates with significantly high grades of students trained conventionally compared with those who practiced with virtual labs (p < 0.001). Students' feedback rates on the virtual labs were high (>70% satisfaction rate). Most students believed virtual labs were supported with a clear explanation, yet they thought it did not give a realistic experience. Students accepted virtual labs, but they still prefer using them as preparatory to classic labs. In conclusion, virtual labs can offer good laboratory practice in the Medical Biochemistry course. Their impact on students' learning might be increased if selected cautiously and implemented properly in the curriculum.

Design and analysis of outcomes following SARS-CoV-2 infection in veterans.

BACKGROUND: Understanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs' (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population. METHODS: In a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts within each month utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes. RESULTS: From an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 39 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%). CONCLUSION: This successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.

Dozee: crafting opportunities during the COVID-19 pandemic [1]

Research methodology: This case was developed from secondary sources. The secondary sources included company websites, social media and news reports. This case has been classroom tested in multiple executive master of business administration (MBA) courses on business model innovation and entrepreneurship. Case overview/synopsis: The case traces the entrepreneurial journey of Dozee, a remote patient monitoring system in India. Dozee was manufactured by Turtle Shell Technologies Private Limited, cofounded by Mudit and Gaurav. The primary customers of Dozee's offering were households with elderly citizens and health-conscious individuals who sought preventive health care. The cofounders identified the unmet need for a convenient and user-friendly contactless health tracker. Dozee team built a thin sensor-embedded sheet and module that can be placed beneath the mattress to track sleep patterns and health vitals. They also provided data analysis and data interpretation services. After four years of conceptualization, Dozee launched its product and service in 2019. Although the initial response was lukewarm, the onset of the COVID-19 crisis led to significant changes in the health-care industry. Demand for virtual assistance and contactless monitoring devices became increasingly important elements of COVID-19 treatment. Unlike other sensor-based fitness trackers, the sheet could be easily placed under the patient's bed to capture health vitals. Choosing to pivot from a home-based individual customer segment to a medical-grade device provider for hospitals could significantly increase the scale and scope of the offering for Dozee, but it would also place Dozee in direct competition with other health monitoring devices from different business categories. Complexity academic level: This case is appropriate for MBA and executive-level courses related to entrepreneurship and business model innovation. The case explores issues such as digital disruption and how start-ups can design a go-to-market strategy. The case works well in the classroom, even if people are unfamiliar with the health-care industry. Participants can certainly relate to the concept of adopting artificial intelligence–enabled devices for monitoring their health. The instructor should be able to quickly engage participants in a lively discussion about Dozee's vision and the opportunities and challenges in adopting digital solutions in health care. © 2022, Emerald Publishing Limited.

Rates of and Factors Associated With Primary and Booster COVID-19 Vaccine Receipt by US Veterans, December 2020 to June 2022.

Importance: COVID-19 vaccination rates remain suboptimal in the US. Identifying factors associated with vaccination can highlight existing gaps and guide targeted interventions to improve vaccination access and uptake. Objective: To describe incidence and patient characteristics associated with primary, first booster, and second booster COVID-19 vaccination in the Veterans Health Administration (VHA). Design, Setting, and Participants: This retrospective cohort study assessed US veterans receiving care in VHA medical centers and outpatient clinics as of December 1, 2020. All VHA enrollees with an inpatient, outpatient, or telehealth encounter in VHA as well as a primary care physician appointment in the preceding 24 months were included. Exposures: Demographic characteristics, place of residence, prior SARS-CoV-2 infection, and underlying medical conditions. Main Outcomes and Measures: Cumulative incidence of primary, first booster, and second booster COVID-19 vaccination through June 2022. Cox proportional hazards regression was used to identify factors independently associated with COVID-19 vaccination. Results: Among 5 632 413 veterans included in the study, 5 094 392 (90.4%) were male, the median (IQR) age was 66 (51-74) years, 1 032 334 (18.3%) were Black, 448 714 (8.0%) were Hispanic, and 4 202 173 (74.6%) were White. Through June 2022, cumulative incidences were 69.0% for primary vaccination, 42.9% for first booster, and 9.3% for second booster. Cumulative incidence for primary vaccination increased with increasing age, from 46.9% (95% CI, 46.8%-47.0%) among veterans aged 18 to 49 years to 82.9% (95% CI, 82.8%-83.0%) among veterans aged 80 to 84 years. More Black veterans completed primary vaccination (71.7%; 95% CI, 71.6%-71.8%) compared with White veterans (68.9%; 95% CI, 68.9%-69.0%), and more urban-dwelling veterans completed primary vaccination (70.9%; 95% CI, 70.9%-71.0%) compared with highly rural-dwelling veterans (63.8%; 95% CI, 63.4%-64.1%). Factors independently associated with higher likelihood of both primary and booster vaccination included older age, female sex, Asian or Black race, Hispanic ethnicity, urban residence, and lack of prior SARS-CoV-2 infection. Conclusions and Relevance: In this cohort study of US veterans, COVID-19 vaccination coverage through June 2022 was suboptimal. Primary vaccination can be improved among younger, rural-dwelling veterans. Greater uptake of booster vaccination among all veterans is needed.

Differences in Emergency Department Sepsis Care: Do Race, Sex, and Language Matter?

Study Objectives: Sepsis accounts for half of hospital deaths and is a priority area of quality measurement and improvement by the Centers for Medicare and Medicaid Services (CMS). Social determinants of health have been associated with sepsis outcomes, with racial and ethnically minoritized patients experiencing higher mortality rates and worse outcomes. Standardization of emergency department (ED) sepsis-care protocols and quality measurement have improved sepsis outcomes and are closely tracked. However, it is unknown whether there are differences in ED sepsis care protocol adherence or outcomes by race, sex, or primary language spoken. The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure is a CMS quality measure used to bundle and track multiple elements of sepsis care that are shown to improve sepsis outcomes. This measure includes obtaining blood cultures and serum lactate measurements and timely administration of intravenous fluid and antibiotics, if indicated. In this study, we hypothesized there would be a difference in 3- hour bundle compliance based on differences in race, sex, and/or language spoken. Method(s): We conducted a retrospective chart review of adult ED patients who met SEP-1 reporting guidelines for severe sepsis, septic shock, or sepsis with organ failure, from April 8, 2019 to January 21, 2022 at a large health system in Rhode Island with over 150,000 annual ED visits. We included patients who had 3-hour bundle compliance reported to CMS. Statistical analysis was completed using univariate descriptive analyses and bivariate analyses with a chi-square test of independence. We conducted logistic regression to identify factors associated with 3-hour sepsis bundle compliance and differences in sepsis treatment by race, ethnicity, sex, primary language spoken, and use of an interpreter, adjusting for emergency severity index (ESI), disposition, inpatient department, and COVID test results. Result(s): The study population included 3,182 patients of which 44.6% (1418/3182) were female, 78.4% (2495/3182) white, and 11.3 % (360/3182) were Hispanic or Latino. The majority (85.5%, 2722/3182) spoke English. Among people who spoke a language other than English, over two-thirds (66.3%, 305/460) received an interpreter. Less than a quarter 23.5% (749/3182) had severe sepsis, over a third (35.5%, 1131/3182) had septic shock, and 40.9% (1302/3182) had sepsis with organ failure. Overall compliance with the SEP-1 bundle was low at 44.9% (1430/3182). There were no significant differences in sepsis bundle compliance by patient sex, race, ethnicity, or language spoken. Logistic regression showed a lower likelihood of compliance with the sepsis bundle among patients with severe sepsis compared to sepsis patients with organ failure (aOR 0.77 [95% CI: 0.65-0.90]). Conclusion(s): Our study did not identify a disparity in SEP-1 bundle compliance by sex, race, ethnicity, or language spoken. These findings support the hypothesis that using standardized ED sepsis protocols and measures are important tools to mitigate and/or prevent disparities in ED sepsis care. We also found low compliance with the SEP-1 bundle, with higher compliance noted among individuals with more severe disease, potentially diluting differences that may exist between demographic groups. Future studies are needed in populations with higher SEP-1 compliance to determine whether there are differences by sex, race, or language spoken. No, authors do not have interests to disclose Copyright © 2022

Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: A subgroup analysis of the SAVE-MORE randomised trial.

Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22-0.50; CCI < 2, OR: 0.38, 95% CI 0.21-0.68; suPAR > 9 ng/mL, OR: 0.35, 95% CI 0.19-0.66; suPAR 6-9 ng/mL, OR: 0.35, 95% CI 0.24-0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25-0.66; and patients <65 years, OR: 0.29, 95% CI 0.19-0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28-0.57) and 0.46 (95% CI 0.32-0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB.

Interferon gamma-induced protein 10 (IP-10) for the early prognosis of the risk for severe respiratory failure and death in COVID-19 pneumonia.

OBJECTIVES: Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19. METHODS: Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death. RESULTS: IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations. CONCLUSIONS: IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment. CLINICALTRIALS: gov, NCT04680949 and NCT04357366.

Risk of Suicide Attempts and Self-Directed Violence after SARS-CoV-2 Infection: Outcomes from an Emulated Trial of a Nationwide Observational Matched Cohort of US Veterans (preprint)

Importance: The negative health-related effects of SARS-CoV-2 infection may include increased risk for self-directed violence. Objective: To assess suicide attempts and other self-directed violence risk among US Veterans with a positive polymerase chain reaction (PCR) test for SARS-CoV-2 infection compared to matched uninfected Veterans. Design, Setting, and Participants: Using a target trial emulation design supported by comprehensive electronic health records from the US Veterans Health Administration, Veterans who had a positive PCR test between March 1, 2020 and March 31, 2021 were matched with non-infected comparators. Monthly matching was anchored to first positive PCR test for each patient. Groups were followed for one-year thereafter. Exposure: Positive SARS-CoV-2 PCR. Main Outcomes and Measures: Suicide attempts and self-directed violence documented in electronic health records by a VHA provider. Hazard ratios (HR) for time to first suicide attempt and self-directed violence (separate models) for the infected versus comparator group were measured using Cox regression models. Analyses were performed for short-term (days 1-30), long-term (days 31-365) and one-year (days 1-365) and further stratified by age and prior self-directed-violence history. Sensitivity analyses included censoring to address comparators crossing over by later testing positive for SARS-CoV-2. Results: Among the 1,190,974 Veterans included, during the one-year period after the index date; 3,078 (0.258%) had a suicide attempt and 2,887 (0.242%) had self-directed violence. Regardless of follow-up duration, the HRs for suicide attempts and self-directed violence were higher for the infected group. For suicide attempts, short-term HR=2.54 (95% Confidence Interval [CI]: 2.05 to 3.15), long-term HR=1.30 (CI: 1.19 to 1.43) and one-year HR= 1.41 (CI: 1.30, 1.54). For self-directed violence, short-term HR=1.94 (CI: 1.51 to 2.49), long-term HR=1.32 (CI: 1.20 to 1.45), and one-year HR=1.38 (CI:1.26, 1.51). Conclusions and Relevance: In matched cohorts, Veterans who had a positive SARS-CoV-2 PCR test had a higher risk of suicide attempt and self-directed violence that were greatest within the first 30 days and present for at least one year following. These findings highlight the importance of assessing patient experiences of suicide attempt and other forms of self-directed violence during different time periods post-infection to identify opportunities to augment prevention efforts and support those affected.

Consensus elements for observational research on COVID-19-related long-term outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its long-term outcomes may be jointly caused by a wide range of clinical, social, and economic characteristics. Studies aiming to identify mechanisms for SARS-CoV-2 morbidity and mortality must measure and account for these characteristics to arrive at unbiased, accurate conclusions. We sought to inform the design, measurement, and analysis of longitudinal studies of long-term outcomes among people infected with SARS-CoV-2. We fielded a survey to an interprofessional group of clinicians and scientists to identify factors associated with SARS-CoV-2 infection and subsequent outcomes. Using an iterative process, we refined the resulting list of factors into a consensus causal diagram relating infection and 12-month mortality. Finally, we operationalized concepts from the causal diagram into minimally sufficient adjustment sets using common medical record data elements. Total 31 investigators identified 49 potential risk factors for and 72 potential consequences of SARS-CoV-2 infection. Risk factors for infection with SARS-CoV-2 were grouped into five domains: demographics, physical health, mental health, personal social, and economic factors, and external social and economic factors. Consequences of coronavirus disease 2019 (COVID-19) were grouped into clinical consequences, social consequences, and economic consequences. Risk factors for SARS-CoV-2 infection were developed into a consensus directed acyclic graph for mortality that included two minimally sufficient adjustment sets. We present a collectively developed and iteratively refined list of data elements for observational research in SARS-CoV-2 infection and disease. By accounting for these elements, studies aimed at identifying causal pathways for long-term outcomes of SARS-CoV-2 infection can be made more informative.

The effect of COVID-19 pandemic on mental health and quality of life in the Athens area - Greece.

This study examines the associations of the COVID -19 pandemic stressors with mental health and quality of life (QoL) of the general population in different demographic areas of Athens. The random sample of the study consisted of 602 participants, 389 (64,6%) women and 213 (35,4%) men residing in Attica (Greece). It was conducted with telephone interviews during the first wave of the pandemic. The instruments used were: World Health Organization Quality of Life Instrument (WHOQOL-BREF), Depression Anxiety Stress Scale (DASS - 21), Body Vigilance Scale (ΒVS), Dimensional Obsessive-Compulsive Scale (Category 1: contamination obsessions -decontamination compulsions) (DOCS) and a set of socio-demographic data and questions on stressors related to the COVID-19 outbreak. A range of statistical analyses were used, including descriptive statistics, examination of the questionnaires' internal consistency, calculating Cronbach's alpha coefficient, as well as multiple linear regression analyses with dependent variables the WHOQOL-BREF, DASS-21, DOCS, and BVS scales. According to the results of our study: a) The greater the extent of negative emotions due to the pandemic and the imposed restrictive measures, such as worry and fear, the higher the score of depression, anxiety, stress, obsessive-compulsive symptomatology, body vigilance and the lower the scores of the WHOQOL domains (Physical Health, Psychological Health, Social Relationships, Environment), b) the fear of being contaminated by the virus seems to have intensified depression-anxiety-stress (DASS-21), obsessive-compulsive (DOCS) and hypochondriacal (BVS) symptomatology. c) The independent variables of depression, stress and anxiety and obsessive - compulsive and hypochondriacal symptomatology were negatively associated with QoL d) The most vulnerable groups in terms of QoL and mental health indicators in our study were those with psychiatric or/and physical illness, the elderly, the unemployed during the lockdown period, those with low educational/ socioeconomic status and those living alone. In conclusion, the negative emotions associated with the COVID-19 outbreak and the imposed restrictive measures had a serious impact on mental health and QoL of the population. This and other similar findings should be taken into account by authorities and decision-makers to prevent and deal with the effects of the pandemic. Unfortunately, the COVID-19 pandemic is still continuing and the imposition of new restrictive measures is considered. This increases the relevance of research like the one presented here.