Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile.

BACKGROUND: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. METHODS: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. RESULTS: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

6 month serologic response to the Pfizer-BioNTech COVID-19 vaccine among healthcare workers.

AIM: Healthcare workers (HCWs) were among the first group of people vaccinated with the Pfizer-BioNTech Covid-19 vaccine (BNT162b2). Characterization of the kinetics of antibody response to vaccination is important to devise future vaccination strategies. To better characterize the antibody response to BNT162b2, we analyzed the kinetics of IgG and IgM antibody response to 5 different SARS-CoV-2 epitopes over a period of 6 months. METHODS AND RESULTS: An observational single-centered study was conducted to evaluate the temporal dynamics of anti-SARS-CoV-2 antibodies following immunization with two doses of BNT162b2. Anti-SARS-CoV-2 antibodies were assessed using the Maverick SARS-CoV-2 multi-antigen panel (Genalyte Inc.). Healthcare workers aged ≥18 receiving BNT162b2 vaccination who self-reported no prior symptoms of COVID-19 nor prior COVID-19 PCR test positivity, were included in this study. HCWs developed an IgG antibody response to SARS-CoV-2 Spike S1, Spike S1 receptor binding domain (RBD), Spike S1S2 and Spike S2 after vaccination. IgG response was observed at two weeks following immunization in most participant samples and continued to increase at week 4, but subsequently decreased significantly starting at 3 months and up to 6 months. In contrast, IgM response to respective epitopes was minimal. CONCLUSION: Multiplex results demonstrate that, contrary to natural infection, immunization with BNT162b2 produces minimal anti-Spike IgM response. Polyclonal IgG response to Spike declined at 3 months and continued to do so up to 6 months.

Hospitalization requiring intensive care unit due to SARS-CoV-2 infection correlated with IgM depression and IgG elevation.

AIM: This study investigated the humoral response against SARS-CoV-2 in patients needing intensive care unit (ICU) care compared with those on general medicine wards. MATERIALS & METHODS: The authors retrospectively reviewed 113 hospitalized patients with COVID-19. They assessed antibody response against five SARS-CoV-2 epitopes at 6-14 days post symptom onset in these patients. RESULTS: Patients with ICU admissions had decreased anti-nucleocapsid immunoglobulin (Ig)M and increased anti-spike IgG compared with patients not requiring the ICU. IgG levels were positively correlated with length of stay. CONCLUSION: Higher levels of IgG against the spike protein correlate with COVID-19 disease severity and length of stay in hospitalized patients. This adds to the knowledge of biochemical response to clinical disease and may help predict ICU needs.

Corrigendum: Emotions and Instructed Language Learning: Proposing a Second Language Emotions and Positive Psychology Model.

[This corrects the article DOI: 10.3389/fpsyg.2020.02142.].

Emotions and Instructed Language Learning: Proposing a Second Language Emotions and Positive Psychology Model.

Although emotion research and positive psychology (PP) have recently gained strong momentum in the field of second language acquisition (SLA), theoretical models linking language emotion and PP research, which offer insights for both research and intervention practice are lacking. To address this gap, the present article first introduces the origin, concept, and research around PP. Next, it summarizes recent research on PP and emotions in SLA. Finally, by triangulating emotion theories and research in the fields of psychology, education, and SLA, we propose a new model, which merges the three pillars of PP (positive institutions, positive characteristics, and positive emotions) with the antecedents, outcomes, and interventions of second language (L2) emotions (the L2EPP model). The value of the model to L2 pedagogy and research is highlighted in the context of the importance of integrating PP into the area of emotions and instructed SLA.

A cross-lagged panel analysis of fear appeal appraisal and student engagement.

BACKGROUND: Fear appeals are persuasive messages given by teachers to students about the importance of avoiding failure in an upcoming high-stakes test. The relationship between the way that students appraise fear appeals and engagement in lessons has not previously been tested using a robust methodological and analytical design that fully controls for concurrent relationships between the variables and stability over time. AIM: The present study addressed these limitations using a cross-lagged panel design to probe reciprocal relationships between students' appraisal of fear appeals as a threat and as a challenge, with their engagement in class. SAMPLE: A total of 2,025 Year 10 and 11 students took part. METHOD: Fear appeal appraisal and student engagement were measured at two time points, 4 months apart. RESULTS: After controlling for unlagged and auto-lagged correlations, and gender and year group, the model fit the data well and six cross-lagged paths emerged as statistically significant. Threat appraisal and emotional engagement were reciprocally, negatively related. Threat appraisal also positively predicted emotional disaffection and challenge appraisal negatively predicted behavioural disaffection. In addition, prospective relations were revealed between specific components of student engagement. CONCLUSIONS: Classroom teachers need to be aware of the possible consequences of making fear appeals and moderate this aspect of their practice accordingly. It would also be beneficial for educational interventions to focus on promoting challenge appraisals of fear appeals.

Provider engagement in precision oncology education: an exploratory analysis of online continuing medical education data.

Given the rapid growth in genomic tests and targeted therapeutics, clinicians are likely to benefit from additional precision medicine education. Aim: This study evaluated the engagement and effectiveness of two interactive, case-based educational modules about somatic tumor testing, developed by the Jackson Laboratory, American Medical Association and Scripps Research Translational Institute, titled 'Precision Medicine for Your Practice'. Results: 402 participants enrolled in one or both free online continuing education modules, including physicians, nurses, scientists and genetic counselors and 41% completed module evaluations. Over 90% of respondents reported alignment of program with practice needs and planned to change their practice, including patient communication, identifying candidates for testing and/or interpreting test results. Conclusion: These findings support Precision Medicine for Your Practice as an effective education offering for diverse clinical professionals.

Acute pancreatitis: should we use antibiotics?

Acute pancreatitis is a common cause of hospitalization and a major source of morbidity worldwide. When it is severe, and especially when it progresses to include necrosis of the pancreas, the risk of infection rises and mortality increases. Early reports suggested prophylactic antibiotics given in severe pancreatitis prevent infection and death. More recent clinical trials do not support this benefit, and meta-analyses on the topic offer conflicting recommendations. In this article, we evaluate the body of published literature examining the use of antibiotics as a preventive measure in acute pancreatitis. The highest quality, currently available data fail to support prophylactic use of antibiotics, which should be added to treatment regimens only where infection has been proven.

Faculty training in evidence-based medicine: improving evidence acquisition and critical appraisal.

INTRODUCTION: Evidence-based medicine (EBM) integrates published clinical evidence with patient values and clinical expertise, the output of which is informed medical decision making. Key skills for evidence-based practice include acquisition and appraisal of clinical information. Faculty clinicians often lack expertise in these skills and are therefore unable to demonstrate this process for students and residents. METHODS: We conducted a yearlong case-based EBM workshop for 28 clinician educators, with precourse and postcourse evaluations of EBM resource use and literature appraisal skills. RESULTS: Of the original 28 participants, 26 completed the course. Self-assessed EBM resource use improved significantly. Self-reported EBM knowledge correlated with measured skill (r = 0.45), and both improved with the intervention (both p < .001). Higher EBM skills scores correlated with time logged on the course's EBM Web sites (r = 0.56; p < .05), workshop attendance rates (r = 0.55; p = .003), and fewer years since medical school graduation (r = -0.56; p < .005). DISCUSSION: An interactive, longitudinal, EBM course derived from a needs assessment can improve 2 skills important for evidence-based practice: online literature retrieval and critical appraisal skills.

Teaching evidence-based medicine on a busy hospitalist service: residents rate a pilot curriculum.

PURPOSE: To increase evidence-based medicine (EBM) instruction within the confines of reduced resident work hours. METHOD: In 2001-02, the authors designed and implemented an EBM curriculum for residents on an inpatient medicine service at Stanford University Medical Center. Thirty-six residents were assigned the hospitalist rotation in its pilot year. Attendings introduced EBM concepts and Internet resources. During daily rounds, housestaff presented patient-based EBM literature search results. After the rotation, residents were given a questionnaire on which they were asked to rate the impact of the curriculum on their understanding of 20 EBM terms or practice skills (1 = no effect to 5 = strong effect). RESULTS: Twenty-three residents (64%) completed the questionnaire. The results were very positive with average effect of more than 4 (somewhat strong effect/impact) for 16 of the 20 questions. High-speed Internet access and EBM Web resources were critical to efficient delivery of the curriculum during inpatient care. CONCLUSION: The pilot curriculum successfully introduced the practice of EBM during active inpatient care without requiring additional hours from housestaff schedules. To further evaluate and expand this project, EBM skills will be tested before and after the rotation, and faculty development will allow consistent delivery in additional clinical settings.