Background Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2005412

Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington.

Background Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is o...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2016638?articleTools=true

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.

Importance Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients. Objective To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19–associated ARDS. Design, Setting, and Participants Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients. Interventions Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148). Main Outcomes and Measures The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days. Results A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38;P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, −1.16; 95% CI, −1.94 to −0.38;P= .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events. Conclusions and Relevance Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days. Trial Registration ClinicalTrials.gov Identifier:NCT04327401

/pdf/effect-of-dexamethasone-on-days-alive-and-ventilator-free-in-1z6emrvlca.pdf

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

Background Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2019014

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

/pdf/extrafollicular-b-cell-responses-correlate-with-neutralizing-uvy9mgl3qb.pdf

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

The REDCap consortium: Building an international community of software platform partners.

Introduction:The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).Methods:We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.Results:The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.Conclusions:Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.

/pdf/a-redcap-based-model-for-electronic-consent-econsent-moving-3dg2ptmaoo.pdf

A REDCap-based model for electronic consent (eConsent): Moving toward a more personalized consent.

REDCap on FHIR: Clinical Data Interoperability Services.

Objectives To share our approach for designing, developing, and deploying the Research Electronic Data Capture (REDCap) Mobile Application, details about its dissemination and support through the REDCap Consortium, and a set of lessons learned and guidance recommendations for others developing mobile platforms to support research in regions or situations with internet scarcity. Materials and Methods We defined minimum viable product requirements centered around Android and iOS platform availability, data capture specifications and project initiation workflow, study data synchronization, and data security. After launch, we added features based on feedback from end-users and REDCap administrators. We prioritized new features based on expected impact, difficulty, and anticipated long-term cost for sustainability. Results We chose Apache Cordova, a combined iOS and Android development framework, based on targeted end-user technology expectations, available programmer resources, and the need to provide solutions for resource-limited settings. The REDCap Mobile Application was launched in 2015, has been enabled at over 800 REDCap Consortium partner organizations, and has supported diverse scientific studies around the world. Discussion Apache Cordova enabled early software releases for both iOS and Android, but required ongoing optimization efforts to improve software responsiveness. Developing a robust and efficient mobile device synchronization architecture was difficult without direct access to global network infrastructures for testing. Research teams in sub-Saharan Africa helped our development team understand and simulate real-world scenarios of intermittent internet connectivity. Conclusion Guidance recommendations based on designing, developing, deploying, and disseminating the REDCap Mobile Application may help other teams looking to develop clinical research informatics applications.

/pdf/the-redcap-mobile-application-a-data-collection-platform-for-2viiswm6zm.pdf

Robert Taylor

Papers

The REDCap consortium: Building an international community of software platform partners.

A REDCap-based model for electronic consent (eConsent): Moving toward a more personalized consent.

REDCap on FHIR: Clinical Data Interoperability Services.

The REDCap Mobile Application: a data collection platform for research in regions or situations with internet scarcity.