Adverse Events and Serological Responses After SARS-CoV-2 Vaccination in Individuals With Inflammatory Bowel Disease.

INTRODUCTION: We determined adverse events after 4 doses of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in those with inflammatory bowel disease (IBD), associations between antibodies and injection site reactions (ISR), and risk of IBD flare. METHODS: Individuals with IBD were interviewed for adverse events to SARS-CoV-2 vaccine. Multivariable linear regression assessed the association between antibody titers and ISR. RESULTS: Severe adverse events occurred in 0.03%. ISR were significantly associated with antibody levels after the fourth dose (geometric mean ratio = 2.56; 95% confidence interval 1.18-5.57). No cases of IBD flare occurred. DISCUSSION: SARS-CoV-2 vaccines are safe for those with IBD. ISR after the fourth dose may indicate increased antibodies.

Mid-term Surgery Outcomes in Patients with COVID-19: Results from a Nationwide Analysis.

OBJECTIVE: Determine mid-term postoperative outcomes among COVID-19-positive patients compared to those who never tested positive before surgery. BACKGROUND: COVID-19 is thought to be associated with prohibitively high rates of postoperative complications. However, prior studies have only evaluated 30-day outcomes and most did not adjust for demographic, clinical, or procedural characteristics. METHODS: We analyzed data from surgeries performed at all Veterans Affairs hospitals between March 2020-2021. Kaplan-Meier curves compared trends in mortality and cox-proportional hazards models estimated rates of mortality and pulmonary, thrombotic, and septic postoperative complications between patients with a positive preoperative SARS-CoV-2 test (COVID (+)) and propensity score matched COVID(-) patients. RESULTS: Of 153,741 surgical patients, 4,778 COVID(+) were matched to 14,101 COVID(-). COVID(+) status was associated with higher postoperative mortality (P<0.0001) with a 6-month survival of 94.2% (95% CI 93.2-95.2 ) versus 96.0% (95.7.0-96.4 ) in COVID(-) . The highest mortality was in the first 30 postoperative days. Hazards for mortality and postoperative complications in COVID(+) decreased with increasing time between testing COVID(+) and date of surgery. COVID(+) patients undergoing elective surgery had similar rates of mortality, thrombotic and septic complications, but higher rates of pulmonary complications than COVID(-) patients. CONCLUSION: This is the first report of mid-term outcomes among COVID-19 patients undergoing surgery. COVID-19 is associated with decreased overall and complication-free survival primarily in the early postoperative period, delaying surgery by 5 weeks or more reduces risk of complications. Case urgency has a multiplicative effect on short- and long-term risk of postoperative mortality and complications.

Rapid Development and Testing of a COVID-19 Vaccine Curriculum for Pediatricians.

BACKGROUND AND OBJECTIVES: As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccines become available to children, pediatricians must navigate vaccination discussions in the setting of rapidly changing vaccine recommendations and approvals. We developed and evaluated an educational curriculum for pediatricians to improve their knowledge about COVID-19 vaccines and confidence in communicating with patients and families about COVID-19 vaccines. METHODS: Five institutions collaborated to develop an online educational curriculum. Utilizing the collaboration's multidisciplinary expertise, we developed a 3-module curriculum focused on the SARS-CoV-2 virus and vaccine basics, logistics and administration of COVID-19 vaccine, and COVID-19 vaccine communication principles. Surveys administered to clinician participants before and after completion of the curriculum assessed knowledge and confidence; a follow-up survey 1 month after the post-survey assessed persistence of initial findings. RESULTS: A total of 152 pediatric providers participated; 72 completed both pre- and post-surveys. The median knowledge score improved from the pre-survey to the post-survey (79%-93%, P < .001). There was an increase in providers' confidence after completing the curriculum, which persisted in the follow-up survey. In the post-survey, 98% of participants had had the opportunity to discuss the COVID-19 vaccine with patients, and most clinicians reported that the modules decreased apprehension some or significantly. CONCLUSIONS: This project demonstrates rapid and feasible deployment of a curriculum providing up-to-date information to front-line clinicians responsible for having complex conversations about COVID-19 vaccine decision-making. Clinicians who completed this curriculum had sustained increased confidence and decreased levels of apprehension when discussing the COVID-19 vaccine.

Rigor, Reproducibility, and Transparency in Shared Research Resources: Follow-Up Survey and Recommendations for Improvements.

Rigor, reproducibility, and transparency (RR&T) are essential components of all scientific pursuits. Shared research resources, also known as core facilities, are on the frontlines of ensuring robust RR&T practices. The Association of Biomolecular Resource Facilities Committee on Core Rigor and Reproducibility conducted a follow-up survey 4 years after the initial 2017 survey to determine if core facilities have seen a positive impact of new RR&T initiatives (including guidance from the National Institutes of Health, new scientific journal requirements on transparency and data provenance, and educational tools from professional organizations). While there were fewer participants in the most recent survey, the respondents' opinions on the role of core facilities and level of best practices adoption remained the same. Overall, the respondents agreed that procedures should be implemented by core facilities to ensure scientific RR&T. They also indicated that there is a strong correlation between institutions that emphasize RR&T and core customers using this expertise in grant applications and publications. The survey also assessed the impact of the COVID-19 pandemic on core operations and RR&T. The answers to these pandemic-related questions revealed that many of the strategies aimed at increasing efficiencies are also best practices related to RR&T, including the development of standard operating procedures, supply chain management, and cross training. Given the consistent and compelling awareness of the importance of RR&T expressed by core directors in 2017 and 2021 contrasted with the lack of apparent improvements over this time period, the authors recommend an adoption of RR&T statements by all core laboratories. Adhering to the RR&T guidelines will result in more efficient training, better compliance, and improved experimental approaches empowering cores to become "rigor champions."

Facilitators and Barriers to Providing Vaccinations During Hospital Visits.

BACKGROUND: Many children are undervaccinated at the time of hospital admission. Our objective was to explore the facilitators and barriers to vaccinating during hospitalization. METHODS: We conducted qualitative interviews of parents, primary care pediatricians, emergency department (ED) physicians, and pediatric hospitalists. Parents of undervaccinated hospitalized children who were admitted through the ED were invited to participate. We used purposive sampling to identify physician participants. Semistructured interviews querying participants' perspectives on hospital-based vaccination were audiorecorded and transcribed. Parent demographics and physician practice characteristics were collected. Transcripts were analyzed for facilitators and barriers to vaccinating during acute hospital visits by using inductive content analysis. A conceptual framework was developed on the basis of the social ecological model. RESULTS: Twenty-one parent interviews and 10 physician interviews were conducted. Of parent participants, 86% were female; 76% were white. Physician participants included 3 primary care pediatricians, 3 ED physicians, and 4 hospitalists. Facilitators and barriers fell under 4 major themes: (1) systems-level factors, (2) physician-level factors, (3) parent-provider interactional factors, and (4) parent- and child-level factors. Parent participants reported a willingness to receive vaccines during hospitalizations, which aligned with physician participants' experiences. Another key facilitator identified by parent and physician participants was the availability of shared immunization data. Identified by parent and physician participants included the availability of shared immunization data. Barriers included being unaware that the child was vaccine-eligible, parental beliefs against vaccination, and ED and inpatient physicians' perceived lack of skills to effectively communicate with vaccine-hesitant parents. CONCLUSIONS: Parents and physicians identified several key facilitators and barriers to vaccinating during hospitalization. Efforts to provide inpatient vaccines need to address existing barriers.

Development of PIVOT with MI: A motivational Interviewing-Based vaccine communication training for pediatric clinicians.

Delay or refusal of childhood vaccines is common and may be increasing. Pediatricians are parents' most trusted source for vaccine information, yet many struggle with how to communicate with parents who resist recommended vaccines. Evidence-based communication strategies for vaccine conversations are lacking. In this manuscript, we describe the development and perceived usefulness of a curriculum to train clinicians on a specific vaccine communication strategy as part of the PIVOT with MI study, a cluster randomized trial testing the effectiveness of this communication strategy on increasing childhood vaccination uptake among 24 pediatric practices in Colorado and Washington. The communication strategy is based on the existing evidence-based communication strategies of a presumptive format for initiating vaccine conversations and use of motivational interviewing if hesitancy persists. Focus groups and semi-structured interviews with pediatric clinicians helped inform the development of the training curriculum, which consisted of an introductory video module followed by 3 training sessions. Between September 2019 and January 2021, 134 pediatric clinicians (92 pediatricians, 42 advanced practice providers) participated in the training as part of the PIVOT with MI study. Of these, 92 % viewed an introductory video module, 93 % attended or viewed a baseline synchronous training, 82 % attended or viewed a 1st refresher training, and 77 % attended or viewed a 2nd refresher training. A follow-up survey was administered August 2020 through March 2021; among respondents (n = 100), >95 % of participants reported that each component of the training program was very or somewhat useful. These data suggest that the PIVOT with MI training intervention is a useful vaccine communication resource with the potential for high engagement among pediatric clinicians.

Tracheostomies of Patients With COVID-19: A Survey of Infection Reported by Health Care Professionals.

BACKGROUND: Health care professionals (HCPs) performing tracheostomies in patients with COVID-19 may be at increased risk of infection. OBJECTIVE: To evaluate factors underlying HCPs' COVID-19 infection and determine whether tracheostomy providers report increased rates of infection. METHODS: An anonymous international survey examining factors associated with COVID-19 infection was made available November 2020 through July 2021 to HCPs at a convenience sample of hospitals, universities, and professional organizations. Infections reported were compared between HCPs involved in tracheostomy on patients with COVID-19 and HCPs who were not involved. RESULTS: Of the 361 respondents (from 33 countries), 50% (n = 179) had performed tracheostomies on patients with COVID-19. Performing tracheostomies on patients with COVID-19 was not associated with increased infection in either univariable (P = .06) or multivariable analysis (odds ratio, 1.48; 95% CI, 0.90-2.46; P = .13). Working in a low- or middle-income country (LMIC) was associated with increased infection in both univariable (P < .001) and multivariable analysis (odds ratio, 2.88; CI, 1.50-5.53; P = .001). CONCLUSIONS: Performing tracheostomy was not associated with COVID-19 infection, suggesting that tracheostomies can be safely performed in infected patients with appropriate precautions. However, HCPs in LMICs may face increased infection risk.

Virtual and In Vitro Antiviral Screening Revive Therapeutic Drugs for COVID-19.

The urgent need for a cure for early phase COVID-19 infected patients critically underlines drug repositioning strategies able to efficiently identify new and reliable treatments by merging computational, experimental, and pharmacokinetic expertise. Here we report new potential therapeutics for COVID-19 identified with a combined virtual and experimental screening strategy and selected among already approved drugs. We used hydroxychloroquine (HCQ), one of the most studied drugs in current clinical trials, as a reference template to screen for structural similarity against a library of almost 4000 approved drugs. The top-ranked drugs, based on structural similarity to HCQ, were selected for in vitro antiviral assessment. Among the selected drugs, both zuclopenthixol and nebivolol efficiently block SARS-CoV-2 infection with EC50 values in the low micromolar range, as confirmed by independent experiments. The anti-SARS-CoV-2 potential of ambroxol, amodiaquine, and its active metabolite (N-monodesethyl amodiaquine) is also discussed. In trying to understand the "hydroxychloroquine" mechanism of action, both pK a and the HCQ aromatic core may play a role. Further, we show that the amodiaquine metabolite and, to a lesser extent, zuclopenthixol and nebivolol are active in a SARS-CoV-2 titer reduction assay. Given the need for improved efficacy and safety, we propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection and discuss their potential use as adjuvant to the current (i.e., remdesivir and favipiravir) COVID-19 therapeutics.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study.

Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either "early" (within 14 d of intubation) or "late" (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, -16 to -8; p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, -23 to -9 d; p < 0.001) and 22 days (95% CI, -31 to -12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0; 95% CI, 1.8-5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Effect of vaccination on the case fatality rate for COVID-19 infections 2020-2021: multivariate modelling of data from the US Department of Veterans Affairs.

OBJECTIVES: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections. DESIGN, SETTING AND PARTICIPANTS: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data-339 772 patients with COVID-19-as of 30 September 2021. OUTCOME MEASURES: The primary outcome for all models was death within 60 days of the diagnosis. Logistic regression was used to derive adjusted ORs for vaccination and infection with Delta versus earlier variants. Models were adjusted for confounding factors, including demographics, comorbidity indices and novel parameters representing prior diagnoses, vital signs/baseline laboratory tests and outpatient treatments. Patients with a Delta infection were divided into eight cohorts based on the time from vaccination to diagnosis. A common model was used to estimate the odds of death associated with vaccination for each cohort relative to that of unvaccinated patients. RESULTS: 9.1% of subjects were vaccinated. 21.5% had the Delta variant. 18 120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for a Delta infection was 1.87±0.05, which corresponds to a relative risk (RR) of 1.78. The overall adjusted OR for prior vaccination was 0.280±0.011 corresponding to an RR of 0.291. Raw CFR rose steadily after 10-14 weeks. The OR for vaccination remained stable for 10-34 weeks. CONCLUSIONS: Our CFR model controls for the severity of confounding factors and priority of vaccination, rather than solely using the presence of comorbidities. Our results confirm that Delta was more lethal than earlier variants and that vaccination is an effective means of preventing death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks. We suggest that this model can be used to evaluate vaccines designed for emerging variants.

Gazing or glancing? Mapping student engagement when film studies moves online

This article presents the findings of a study undertaken by a team of three film studies teacher-researchers working with undergraduate students in a course titled 'Histories of Film Theory'. In the context of the transition from face-to-face to remote learning during the COVID-19 pandemic, the authors observed that students' approaches to understanding relevant film theories became increasingly inflected by their experiences of contrasting methods of course delivery, such as that between the cinema theatre or home viewing environment. To investigate this effect, the authors conducted a study of student experience across the 2020 and 2021 cohorts;the purpose was to understand how the shift to online learning shaped students' engagement with set film texts, by analysing the behaviour exhibited when accessing film texts remotely. The study is grounded in the observation that there is an existing body of film theory on screen spectatorship that has potential significance to a scholarly understanding of the pedagogical complexity of online learning and multimodal literacies. This scholarship ranges from analyses of 'traditional' reception environments (Baudry 1974), to accounts of the differentiation in modes of attention introduced by new media (Ellis 1992, Cavell 1982), to analyses of the multiplying second screen practices of the digital era (Casetti 2011). A governing distinction highlighted in the results is between 'gazing', the mode of spectatorship associated with the traditional cinema experience, and 'glancing', the mode associated with home viewing and second screen use. Were the students in the course gazing or glancing, and how did this affect their encounters with films and characterize their remote learning experience more broadly? In asking these questions, the article demonstrates how the intellectual resources of film studies might be applied to contemporary digital pedagogy scholarship to reveal a complex scenario in which remote learning practices both hinder and enhance learning experiences, sometimes simultaneously.

Variations in COVID-19 impacts by social vulnerability in Philadelphia, June 2020-December 2022 (preprint)

Introduction: The study objective was to elucidate the relationship between social vulnerability and COVID-19 impacts in Philadelphia between June 2020 and December 2022. Methods: Using publicly available COVID-19 case, test, hospitalization, and mortality data for Philadelphia (June 7, 2020-December 31, 2022) and area-level social vulnerability data, we compared the incidence, test positivity, hospitalization, and mortality rates in high and low vulnerability neighborhoods of Philadelphia, characterized as scoring above or below the national median score on the social vulnerability index. We used linear mixed effects models to test the association between social vulnerability and COVID-19 incidence, test positivity, hospitalization, and mortality rates, adjusting for time and age distribution. Results: 90.4% of Philadelphians (n = 1,430,153) live in neighborhoods classified as socially vulnerable, based on scoring above the national median score on the social vulnerability index. COVID-19 incidence, hospitalization, and mortality rates were significantly elevated in the more vulnerable communities, with p < 0.05, p < 0.005, and p < 0.001, respectively. The relative risks of COVID-19-related incidence, hospitalization, and death, comparing the more vulnerable neighborhoods to the less vulnerable neighborhoods, were 1.11 (95%CI: 1.10-1.12), 2.07 (95%CI: 1.93-2.20), and 2.06 (95%CI: 1.78-2.38), respectively. Thus, between June 7, 2020 and December 31, 2022, 32,573 COVID-19 cases, 9,409 hospitalizations, and 1,967 deaths would have been avoided in Philadelphias more vulnerable communities had they experienced the same rates of incidence, hospitalization, and death as the less vulnerable Philadelphia communities. Conclusions: These results highlight the disparate morbidity and mortality experienced by people living in more vulnerable neighborhoods in a large US city. Importantly, our findings illustrate the importance of designing public health policies and interventions with an equity-driven approach, with greater resources and more intensive prevention strategies applied in socially vulnerable communities.

A B1a-natural IgG-neutrophil axis is impaired in viral- and steroid-associated aspergillosis.

The lung naturally resists Aspergillus fumigatus (Af) in healthy individuals, but multiple conditions can disrupt this resistance, leading to lethal invasive infections. Core processes of natural resistance and its breakdown are undefined. We investigated three distinct conditions predisposing to lethal aspergillosis-severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, influenza A viral pneumonia, and systemic corticosteroid use-in human patients and murine models. We found a conserved and essential coupling of innate B1a lymphocytes, Af-binding natural immunoglobulin G antibodies, and lung neutrophils. Failure of this axis concealed Af from neutrophils, allowing rapid fungal invasion and disease. Reconstituting the axis with immunoglobulin therapy reestablished resistance, thus representing a realistic pathway to repurpose currently available therapies. Together, we report a vital host resistance pathway that is responsible for protecting against life-threatening aspergillosis in the context of distinct susceptibilities.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study

OBJECTIVES: Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either “early” (within 14 d of intubation) or “late” (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, –16 to –8;p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, –23 to –9 d;p < 0.001) and 22 days (95% CI, –31 to –12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0;95% CI, 1.8–5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.