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.

A developmental perspective on sleep consistency: Preschool age through emerging adulthood.

OBJECTIVE/BACKGROUND: Beyond sleep duration, the regularity of sleep patterns (e.g., sleep consistency), including variability in sleep timing (e.g., bedtime, wake time) and duration, is a critical marker of sleep health. Sleep consistency is captured using a variety of methods within the literature (e.g., sleep intraindividual variability, social jetlag), but most of the research focuses on adolescents. METHODS: Drawing on a developmental perspective, this narrative review highlights how normative changes at the individual (e.g., biological, cognitive, and social) and contextual (e.g., home, school, sociocultural) levels may contribute to inconsistent sleep patterns across development. RESULTS AND CONCLUSIONS: This review emphasizes how inconsistent sleep may increase across pivotal transitions throughout development (e.g., elimination of naps, puberty, summertime, entering college). Finally, recommendations for measuring sleep consistency and areas to address in future research are discussed.

Sleep, Affect, and Emotion Reactivity in First-Year College Students: A Daily Diary Study.

BACKGROUND: Sleep is an important factor in well-being, especially during the transition to college when academic and social commitments increase. Identifying factors that contribute to poor sleep (including short duration and increased variability in duration) can support development of interventions. Affect and emotion reactivity are factors that could contribute to sleep, and have not been studied in relation to sleep variables among first-year college students during their adjustment to the college environment. This adjustment might be difficult for some students, and therefore elicit affect fluctuations that contribute to poor sleep. Alternatively, sleep could contribute to daily affect. The present daily diary study examined bidirectional relations between daily sleep and affect, as well as between emotion reactivity and sleep (duration and variability) and affect (daily and overall variability) in first-year college students. METHOD: First-year college students (n = 244; 86.1% female) completed a baseline survey including measures of emotion reactivity and anxiety and depressive symptoms, followed by 7 days of a once-per-day diary, reporting on their affect and sleep duration. RESULTS: On days when individuals reported increased sleep duration, they also tended to experience greater positive affect the following day (p = .01). Those who experienced high levels of emotion reactivity also experienced more negative affect (p < .001) and negative affect variability (p < .001). CONCLUSION: Emotion reactivity might identify college students who experience more negative affect and are possibly at risk to develop mental health disorders. The importance of sleep health should continue to be emphasized to students as they transition to college.

Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions.

Regional connectivity and land travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding in the early pandemic to more regional seeding for the travel restrictions period. We show that land travel, particularly freight transport, drove introduction risk during the travel restrictions period. High regional connectivity and land travel also drove Jordan's export risk. Our findings emphasize regional connectedness and land travel as drivers of transmission in the Middle East.

Artificial intelligence in healthcare: a primer for medical education in radiomics.

The application of artificial intelligence (AI) to healthcare has garnered significant enthusiasm in recent years. Despite the adoption of new analytic approaches, medical education on AI is lacking. We aim to create a usable AI primer for medical education. We discuss how to generate a clinical question involving AI, what data are suitable for AI research, how to prepare a dataset for training and how to determine if the output has clinical utility. To illustrate this process, we focused on an example of how medical imaging is employed in designing a machine learning model. Our proposed medical education curriculum addresses AI's potential and limitations for enhancing clinicians' skills in research, applied statistics and care delivery.

The application of artificial intelligence (AI) to healthcare has generated increasing interest in recent years; however, medical education on AI is lacking. With this primer, we provide an overview on how to understand AI, gain exposure to machine learning (ML) and how to develop research questions utilizing ML. Using an example of a ML application in imaging, we provide a practical approach to understanding and executing a ML analysis. Our proposed medical education curriculum provides a framework for healthcare education which we hope will propel healthcare institutions to implement ML laboratories and training environments and improve access to this transformative paradigm.

Daily relations between nap occurrence, duration, and timing and nocturnal sleep patterns in college students.

OBJECTIVE/DESIGN: Sleep patterns change during college, and students may nap to compensate for lost sleep. Despite the increased prevalence of napping among students, few studies have investigated daily relations between napping and nocturnal sleep, as well as how timing of naps and nocturnal sleep might influence one another. The present study used daily diaries to capture the occurrence, timing, and duration of napping and relation to nocturnal sleep. SETTING/PARTICIPANTS: Daily diary data, collected for 4-7 days, from 654 college students from a mid-sized midwestern university (81.5% female). MEASUREMENT: Participants reported nightly sleep durations, bedtimes, and wake times as well as nap durations and nap start times. RESULTS: Multilevel modeling (MLM) and multi-level logistic regressions revealed bidirectional relations between nocturnal sleep and napping. Regarding nocturnal sleep and its relation to next day napping, nocturnal sleep (including shorter duration and later bedtime) was associated with increased odds of napping and longer napping the following day. Shorter sleep duration was also associated with taking an earlier nap, while later bedtime was associated with a later nap the following day. Regarding napping and its association with same-night nocturnal sleep, taking a nap was associated with longer sleep duration that night, however, later nap start times and longer nap durations were associated with later bedtimes that night. CONCLUSIONS: Findings provide evidence for bidirectional associations between napping and nocturnal sleep. Future studies are needed to explore how naps could be optimized to promote nocturnal sleep among college students, as well as for whom naps might be most beneficial.

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.

Delicious and difficult to resist?: Inhibitory control differs in young women after exposure to food and non-food commercials.

Unhealthy food marketing, a ubiquitous food stimulus, may impact response inhibition, making it more difficult to maintain healthy eating behaviors. Individuals with disordered eating may be particularly susceptible to altered inhibition responses to food stimuli, making them more vulnerable to unhealthy food marketing, which could perpetuate their disordered eating behaviors. The present study examined response inhibition following exposure to food commercials in young women who reported either high levels of disordered eating (HEC) or low/no disordered eating (LEC) (N = 27; age: M = 19.28, SD = 1.01) by measuring event related potentials (ERPs) during a stop-signal task embedded with food stimuli. Results indicated that participants had significantly higher accuracy on stop trials displaying unhealthy food stimuli than trials displaying healthy food stimuli after viewing non-food commercials but displayed no difference after viewing food commercials. LEC individuals displayed a smaller N200/P300 amplitude in response to food stimuli on the stop-signal task after watching food commercials as compared to non-food commercials, but this difference did not exist for HEC individuals. Results indicate that unhealthy food commercials may impact behavioral and electrophysiological correlates of response inhibition evoked by food stimuli in young women, and individuals with disordered eating might actually be less responsive to food marketing than those without disordered eating.

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.

Activity measurement in pediatric chronic fatigue syndrome.

OBJECTIVES: Individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) experience debilitating symptoms, including post-exertional malaise, an intensification of symptoms after physical or cognitive exertion. Previous studies found differences in the activity levels and patterns of activity among individuals with ME and CFS, compared to healthy controls; however, limited research exists on the activity levels of pediatric patients. The objective of this study was to examine differences in activity between healthy children and youth with ME and CFS. METHODS: The present study examines the objective (i.e., ActiGraphy) and self-reported levels of activity among children (ages 5 to 17) enrolled in a community-based study of pediatric CFS. RESULTS: Children with ME and CFS evidenced lower activity levels than healthy control children. Moreover, participants with ME and CFS evidenced increased nighttime activity and delayed initiation of daytime activity. Participants' self-reported activity data significantly correlated with their ActiGraph data, suggesting that children with ME and CFS are able to accurately describe their activity level. DISCUSSION: This study highlights differences in activity level and diurnal/nocturnal activity patterns between healthy children and those with ME and CFS. These differences should be considered in identifying appropriate supports and accommodations for children with ME and CFS.

Evaluation of Communication and Safety Behaviors During Hospital-Wide Code Response Simulation.

INTRODUCTION: To understand the baseline quality of team communication behaviors at our organization, we implemented institution-wide simulation training and measured the performance of safety behaviors of ad hoc teams in emergent situations. METHODS: Clinicians participated in 2 interprofessional video-recorded simulation scenarios, each followed by debriefing. Using a standardized evaluation instrument, 2 reviewers independently evaluated the presence or absence of desired team safety behaviors, including escalating care, sharing a mental model, establishing leadership, thinking out loud, and identifying roles and responsibilities. We also scored the quality of sharing the mental model, closed-loop communication, and overall team performance on a 7-point scale. Discordant reviews were resolved with scoring by an additional reviewer. RESULTS: A total of 1404 clinicians participated in 398 simulation scenarios, resulting in 257 usable videos. Overall, teams exhibited desired behaviors at the following frequencies: escalating care, 85%; sharing mental models, 66%; verbally establishing leadership, 6%; thinking out loud, 87%; and identifying roles and responsibilities, 27%. Across all reviews, the quality of the graded behaviors (of 7 points) was 2.8 for shared mental models, 3.3 for closed-loop communication, and 3.2 for overall team performance. CONCLUSIONS: In a simulation setting with ad hoc teams, there was variable performance on completing safety behaviors and only a fair quality of graded communication behaviors. These results establish a baseline assessment of communication and teamwork behaviors and will guide future quality improvement interventions.

Green schoolyard renovations in low-income urban neighborhoods: Benefits to students, schools, and the surrounding community.

Green schoolyards may buffer against the effects of urbanization through increasing access to nature and its benefits. The present study was a community-academic partnership that examined the effects of green schoolyard renovations on utilization, physical activity (PA), and social interactions as well as perceptions of safety, neighborhood climate, and social cohesion among those living in low-income, urban neighborhoods. Utilizing behavioral mapping techniques and multi-informant surveys (i.e., caregivers, teachers, and community members), changes from pre- to postrenovation were assessed at two low-income, urban schools. Behavioral mapping results demonstrated increases in utilization and prosocial interactions among youth from pre- to postrenovation. Levels of moderate-to-vigorous PA also increased from pre- to postrenovation at one school. Survey data from community stakeholders revealed improvements in the perception of schoolyard safety and school-community relationships as well as reductions in bullying postrenovation. Green schoolyards may offer a safe space for children and adults to engage in social, outdoor activities, particularly in low-income, urban neighborhoods.

Innovative Hospital-Based Pediatric Virtual Learning for Nursing Students.

BACKGROUND/PROBLEM: Specialty clinical sites, including pediatrics, are historically scarce in prelicensure nursing education. APPROACH: Simulation educators developed the Pediatric Virtual Clinical Learning Series (PVCLS) containing 4 virtual learning modules designed to enhance knowledge and skills of prelicensure nursing students in clinical pediatric care. Topics included documentation, rapid response, code blue, and a pediatric case. The learning sessions were initially offered as synchronous virtual classes and were then posted on our e-learning platform to serve as enduring asynchronous material. The target audience was nursing students and faculty from regional and nationally affiliated nursing schools with the pediatric hospital. OUTCOMES: Faculty and 185 nursing students participated in the synchronous or asynchronous learning sessions. Students' ratings that the virtual classes met their personal expectations were 4.02 to 4.56 of 5 for the synchronous sessions and 3.41 to 3.58 of 4 for the asynchronous sessions. CONCLUSIONS: The PVCLS provided both synchronous and asynchronous learning experiences to fill a widening knowledge gap in pediatrics.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Life Interrupted: Family Routines Buffer Stress during the COVID-19 Pandemic.

Adoption of certain behavioral and social routines that organize and structure the home environment may help families navigate the challenges presented by the COVID-19 pandemic. The current cross-sectional study aimed to assess family routines prior to and during the COVID-19 pandemic and examine associations with individual and family well-being. Using a national sample, 300 caregivers of children ages 6-18 were surveyed using Amazon Mechanical Turk platform during the first three months of COVID-19 pandemic in the United States. Caregivers reported on family demographics, COVID-19-related stress, engagement in family routines (prior to and during the COVID-19 pandemic), stress mindset, self-efficacy, and family resiliency. Overall, families reported engaging in fewer routines during the COVID-19 pandemic compared to prior to the pandemic. COVID-19-related stress was highest in low-income families, families of healthcare workers, and among caregivers who had experienced the COVID-19 virus. Moreover, COVID-19-related stress was negatively related to self-efficacy, positively related to an enhancing stress mindset, and negatively related to family resilience. Engagement in family routines buffered relations between COVID-19-related stress and family resilience, such that COVID-19-related stress was not associated with lower family resilience among families that engaged in high levels of family routines. Results suggest that family routines were challenging to maintain in the context of the COVID-19 pandemic, but were associated with better individual and family well-being during this period of acute health, economic, and social stress.

Code Response Training: Improving Interprofessional Communication.

Introduction: Using simulation to improve team performance in emergencies is commonplace. Decreasing codes hospital-wide can be challenging. To address these needs, hospital leaders requested a simulation program to provide team training across an institution focused on patient safety and communication techniques. Methods: We developed a multimodal approach pairing three online modules on communication techniques with a simulation-based learning session. The three modules required 1 hour, followed by a 1-hour, in-person, simulation-based, interprofessional, small-group session of clinical staff. In ad hoc teams, participants managed two cases: a toddler with airway obstruction and a child developing septic shock. A focused debriefing included discussion of mental models, team formation and expertise, and communication techniques to create a common language to use in ad hoc team formation and patient care. Results: Through more than 200 training sessions reaching over 1,400 staff members, we executed code response training. A nurse and physician facilitated each session, emphasizing the interprofessional nature needed for patient care. Participants rated the learning experience highly on a 5-point Likert scale (1 = low/poor, 5 = high/excellent), with an average rating of 4.3 for achieving objectives and an average rating of 4.8 for facilitator effectiveness. Discussion: Through engaging leadership and frontline clinicians, the simulation program provided code response training hospital-wide, emphasizing the importance of teamwork and communication in critical situations. Such hospital-wide training can emphasize a shared language to empower clinicians at all levels to deliver safe, quality patient care.

Durvalumab-induced myocarditis, myositis, and myasthenia gravis: a case report.

BACKGROUND: Immune checkpoint inhibitors are effective therapies for a wide range of malignancies. Their increased use has led to a wide range of immune-related adverse effects including skin, gastrointestinal, pulmonary, endocrine, cardiac, and neurologic complications. CASE PRESENTATION: We present the case of a 72-year-old Caucasian man with non-small cell lung cancer who was admitted for dyspnea after two cycles of durvalumab. He was found to have significantly elevated levels of serum creatinine kinase and troponin with a negative cardiac catheterization. During his hospitalization, he developed progressive dyspnea and new-onset axial weakness, ultimately leading to the diagnosis of durvalumab-induced myocarditis, myasthenia gravis, and myositis. CONCLUSION: This is, to our knowledge, the first reported case of anti-programmed cell death ligand 1-induced combination of myocarditis, myasthenia gravis, and myositis. While the use of immunologic agents has resulted in overall improved cancer outcomes, their increased use has led to a vast spectrum of immune-related adverse effects. We review the diagnostic workup and management of patients with these immune-related adverse effects, underscoring the importance of early identification given the potential for rapid deterioration.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

Healthcare worker seroconversion for SARS-CoV-2 at two large health systems in San Diego.

Coronavirus Disease 2019 infections among healthcare workers were widely reported in China and Europe as the pandemic expanded to the United States. In order to examine the infection rate among these essential workers, we combined results of SARS-CoV-2 serology testing offered free to healthcare workers at two large San Diego health systems when the antibody assays first became available.