A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

The Effect of Implementation of Guideline Order Bundles Into a General Admission Order Set on Clinical Practice Guideline Adoption: Quasi-Experimental Study.

BACKGROUND: Clinical practice guidelines (CPGs) and associated order sets can help standardize patient care and lead to higher-value patient care. However, difficult access and poor usability of these order sets can result in lower use rates and reduce the CPGs' impact on clinical outcomes. At our institution, we identified multiple CPGs for general pediatrics admissions where the appropriate order set was used in <50% of eligible encounters, leading to decreased adoption of CPG recommendations. OBJECTIVE: We aimed to determine how integrating disease-specific order groups into a common general admission order set influences adoption of CPG-specific order bundles for patients meeting CPG inclusion criteria admitted to the general pediatrics service. METHODS: We integrated order bundles for asthma, heavy menstrual bleeding, musculoskeletal infection, migraine, and pneumonia into a common general pediatrics order set. We compared pre- and postimplementation order bundle use rates for eligible encounters at both an intervention and nonintervention site for integrated CPGs. We also assessed order bundle adoption for nonintegrated CPGs, including bronchiolitis, acute gastroenteritis, and croup. In a post hoc analysis of encounters without order bundle use, we compared the pre- and postintervention frequency of diagnostic uncertainty at the time of admission. RESULTS: CPG order bundle use rates for incorporated CPGs increased by +9.8% (from 629/856, 73.5% to 405/486, 83.3%) at the intervention site and by +5.1% (896/1351, 66.3% to 509/713, 71.4%) at the nonintervention site. Order bundle adoption for nonintegrated CPGs decreased from 84% (536/638) to 68.5% (148/216), driven primarily by decreases in bronchiolitis order bundle adoption in the setting of the COVID-19 pandemic. Diagnostic uncertainty was more common in admissions without CPG order bundle use after implementation (28/227, 12.3% vs 19/81, 23.4%). CONCLUSIONS: The integration of CPG-specific order bundles into a general admission order set improved overall CPG adoption. However, integrating only some CPGs may reduce adoption of order bundles for excluded CPGs. Diagnostic uncertainty at the time of admission is likely an underrecognized barrier to guideline adherence that is not addressed by an integrated admission order set.

EMBRACE: One Small Story in Lupus-One Giant Challenge in Clinical Trials.

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post-marketing commitment to the Food and Drug Administration. The study recruited only patients who self-identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well-designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long-term support to ensure equity in the process, products, and benefits from drug development and clinical trials.

Tracking COVID-19 Discourse on Twitter in North America: Infodemiology Study Using Topic Modeling and Aspect-Based Sentiment Analysis.

BACKGROUND: Social media is a rich source where we can learn about people's reactions to social issues. As COVID-19 has impacted people's lives, it is essential to capture how people react to public health interventions and understand their concerns. OBJECTIVE: We aim to investigate people's reactions and concerns about COVID-19 in North America, especially in Canada. METHODS: We analyzed COVID-19-related tweets using topic modeling and aspect-based sentiment analysis (ABSA), and interpreted the results with public health experts. To generate insights on the effectiveness of specific public health interventions for COVID-19, we compared timelines of topics discussed with the timing of implementation of interventions, synergistically including information on people's sentiment about COVID-19-related aspects in our analysis. In addition, to further investigate anti-Asian racism, we compared timelines of sentiments for Asians and Canadians. RESULTS: Topic modeling identified 20 topics, and public health experts provided interpretations of the topics based on top-ranked words and representative tweets for each topic. The interpretation and timeline analysis showed that the discovered topics and their trend are highly related to public health promotions and interventions such as physical distancing, border restrictions, handwashing, staying home, and face coverings. After training the data using ABSA with human-in-the-loop, we obtained 545 aspect terms (eg, "vaccines," "economy," and "masks") and 60 opinion terms such as "infectious" (negative) and "professional" (positive), which were used for inference of sentiments of 20 key aspects selected by public health experts. The results showed negative sentiments related to the overall outbreak, misinformation and Asians, and positive sentiments related to physical distancing. CONCLUSIONS: Analyses using natural language processing techniques with domain expert involvement can produce useful information for public health. This study is the first to analyze COVID-19-related tweets in Canada in comparison with tweets in the United States by using topic modeling and human-in-the-loop domain-specific ABSA. This kind of information could help public health agencies to understand public concerns as well as what public health messages are resonating in our populations who use Twitter, which can be helpful for public health agencies when designing a policy for new interventions.

When is it safe to perform abdominal transplantation in patients with prior SARS-CoV-2 infection: A case series.

BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.