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Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.

Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity—defined by the level of antibodies—is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses. The extent of antibody protection against SARS-CoV-2 remains unclear. Here, using a cohort of 120 seroconverted individuals, the authors longitudinally characterize neutralization, Fc-function, and SARS-CoV-2 specific T cell responses, which they show to be prominent only in those subjects that elicited receptor-binding domain (RBD)-specific antibody titers above a certain threshold, suggesting that development of T cell responses to be related to anti-RBD Ab production.

Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.

Background Visits to the emergency department (ED) are inflection points in patients’ illness trajectories and are an underutilized setting to engage seriously ill patients in conversations about their goals of care. We developed an intervention ( ED GOAL ) that primes seriously ill patients to discuss their goals of care with their outpatient clinicians after leaving the ED. The aims of this study are (i) to test the impact of ED GOAL administered by trained nurses on self-reported, advance care planning (ACP) engagement after leaving the ED and (ii) to evaluate whether ED GOAL increases self-reported completion of serious illness conversation and other patient-centered outcomes. Methods This is a two-armed, parallel-design, single-blinded, randomized controlled trial of 120 seriously ill older adults in two academic and one community EDs in Boston, MA. Participants are English-speaking adults 50 years and older with a serious life-limiting illness with a recent ED visit. Patients with a valid MOLST (medical order for life-sustaining treatment) form or other documented goals of care within the last 3 months are excluded. We enroll the caregivers of patients with cognitive impairment. Patients are assigned to the intervention or control group using block randomization. A blinded research team member will perform outcome assessments. We will assess (i) changes in ACP engagement within 6 months and (ii) qualitative assessments of the effect of ED GOAL . Discussion In seriously ill older adults arriving in the ED, this randomized controlled trial will test the effects of ED GOAL on patients’ self-reported ACP engagement, EMR documentation of new serious illness conversations, and improving patient-centered outcomes. Trial registration ClinicalTrials.gov identifier: NCT05209880

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.

Introduction: Acute musculoskeletal back pain is a frequent cause of emergency department (ED) visits, often with suboptimal relief from standard treatments. Recent evidence suggests listening to music may modulate pain and anxiety. In this pilot randomized controlled trial, we evaluated the impact of a brief session of patient-selected music vs noise cancellation on pain severity and anxiety in patients presenting to the ED with back pain. Methods: Patients with acute back pain completed a baseline survey to assess demographics, medication information, and psychosocial factors. The ED patients were randomized to listen to self-selected music or to noise cancellation (control). Patients rated their pain and anxiety (0-10) before and immediately after the intervention. We used analyses of covariance to examine whether post-intervention pain and anxiety differed between the groups, while controlling for baseline trait pain catastrophizing. A mediation analysis was conducted to explore the role of post-intervention anxiety as a mediator of the group difference in post-intervention pain. Results: Forty patients were enrolled with an average age of 47.2 years (range 21 - 81). and 27 patients (68%) were female. At baseline, patients in the music group reported higher pain catastrophizing compared to patients in the noise cancellation group. There were no other group differences in baseline characteristics. Post-intervention, patients in the music group reported significantly lower anxiety (3.0 ± 0.7 vs 5.5 ± 0.7, P = 0.016) and pain severity (6.1 ± 0.4 vs.7.5 ± 0.4, P = 0.037) compared to the noise cancellation group. A mediation analysis showed that post-intervention anxiety partially mediated the association between intervention group (music vs noise cancellation) and post-intervention pain. Conclusion: A brief session of self-selected music resulted in lower pain and anxiety scores than noise cancellation among patients with musculoskeletal back pain in the ED. Patients who listened to music reported lower post-intervention anxiety, which partially contributed to lower post-intervention pain severity.

Vocal biomarker-based machine learning approaches have shown promising results in the detection of various health conditions, including respiratory diseases, such as asthma. This study aimed to determine whether a respiratory-responsive vocal biomarker (RRVB) model platform initially trained on an asthma and healthy volunteer (HV) data set can differentiate patients with active COVID-19 infection from asymptomatic HVs by assessing its sensitivity, specificity, and odds ratio (OR). A logistic regression model using a weighted sum of voice acoustic features was previously trained and validated on a data set of approximately 1700 patients with a confirmed asthma diagnosis and a similar number of healthy controls. The same model has shown generalizability to patients with chronic obstructive pulmonary disease, interstitial lung disease, and cough. In this study, 497 participants (female: n=268, 53.9%; <65 years old: n=467, 94%; Marathi speakers: n=253, 50.9%; English speakers: n=223, 44.9%; Spanish speakers: n=25, 5%) were enrolled across 4 clinical sites in the United States and India and provided voice samples and symptom reports on their personal smartphones. The participants included patients who are symptomatic COVID-19 positive and negative as well as asymptomatic HVs. The RRVB model performance was assessed by comparing it with the clinical diagnosis of COVID-19 confirmed by reverse transcriptase-polymerase chain reaction. The ability of the RRVB model to differentiate patients with respiratory conditions from healthy controls was previously demonstrated on validation data in asthma, chronic obstructive pulmonary disease, interstitial lung disease, and cough, with ORs of 4.3, 9.1, 3.1, and 3.9, respectively. The same RRVB model in this study in COVID-19 performed with a sensitivity of 73.2%, specificity of 62.9%, and OR of 4.64 (P<.001). Patients who experienced respiratory symptoms were detected more frequently than those who did not experience respiratory symptoms and completely asymptomatic patients (sensitivity: 78.4% vs 67.4% vs 68%, respectively). The RRVB model has shown good generalizability across respiratory conditions, geographies, and languages. Results using data set of patients with COVID-19 demonstrate its meaningful potential to serve as a prescreening tool for identifying individuals at risk for COVID-19 infection in combination with temperature and symptom reports. Although not a COVID-19 test, these results suggest that the RRVB model can encourage targeted testing. Moreover, the generalizability of this model for detecting respiratory symptoms across different linguistic and geographic contexts suggests a potential path for the development and validation of voice-based tools for broader disease surveillance and monitoring applications in the future.

The integration of online learning in health professions education has grown rapidly, offering flexibility to learners worldwide. Asynchronous online learning allows residents to engage with educational content at a time convenient for them, accommodating their demanding schedules. This study aims to reveal how residents approach asynchronous online learning during their residency training. The Resident Study Log, an asynchronous learning tool, was introduced in a teaching hospital in Japan. This tool facilitated residents to share daily reflections on their learning experiences, allowing supervising physicians outside of their regular clinical teams to provide feedback. Posts shared between April 2020 and July 2021 were reviewed. The outcome measured included the frequency and timing of posts as well as residents' satisfaction and perceived burden, which were assessed through anonymous surveys. A total of 31 residents participated during the study period, posting 599 entries on the Resident Study Log, averaging one post per resident every two days. Participants reported an average satisfaction score of 5.3 out of 6.0 (6-point Likert scale, where 1 indicated 'not satisfied at all' and 6 indicated 'very satisfied'), while the perceived burden averaged 4.0 out of 6.0 (6-point Likert scale, where 1 indicated 'not burdensome at all' and 6 indicated 'very burdensome'). Notably, posting activity peaked at around 23:00, with 17.4% of posts created between midnight and 5:00. The Resident Study Log was a simple, low-cost tool, with high satisfaction levels among residents. However, the late-night posting pattern raises concerns about resident well-being and sleep hygiene. As asynchronous learning is increasingly more prevalent, it is crucial to ensure it does not inadvertently impose hidden burdens on learners' overall well-being.

Emergency clinicians face elevated rates of burnout that result in poor outcomes for clinicians, patients, and health systems. The objective of this single‐arm pilot study was to evaluate the feasibility of a Transcendental Meditation (TM) intervention for emergency clinicians during the coronavirus disease 2019 (COVID‐19) pandemic and to explore the potential effectiveness in improving burnout, sleep, and psychological health. Emergency clinicians (physicians, nurses, and physician‐assistants) from 2 urban hospitals were recruited to participate in TM instruction (8 individual or group in‐person and remote sessions) for 3 months. Session attendance was the primary feasibility outcome (prespecified as attending 6/8 sessions), and burnout was the primary clinical outcome. Participant‐reported measures of feasibility and validated measures of burnout, depression, anxiety, sleep disturbance, and stress were collected at baseline and the 1‐month and 3‐month follow‐ups. Descriptive statistics and linear mixed‐effects models were used. Of the 14 physicians (46%), 7 nurses (22%), and 10 physician‐assistants (32%) who participated, 61% were female (n = 19/32). TM training and at‐home meditation practice was feasible for clinicians as 90.6% (n = 29/32) attended 6/8 training sessions and 80.6% self‐reported meditating at least once a day on average. Participants demonstrated significant reductions in burnout (P < .05; effect sizes, Cohen's d= 0.43–0.45) and in symptoms of depression, anxiety, stress, and sleep disturbance (P values < .001; Cohen's d= 0.70–0.87). TM training was feasible for emergency clinicians during the COVID‐19 pandemic and led to significant reductions in burnout and psychological symptoms. TM is a safe and effective meditation tool to improve clinicians’ well‐being.

Emergency physicians face the challenge of relieving acute pain daily. While opioids are a potent treatment for pain, the opioid epidemic has ignited a search for nonopioid analgesic alternatives that may decrease the dose or duration of opioid exposure. While behavioral therapies and complementary medicine are effective, they are difficult to deploy in the emergency department. Music is a potential adjunctive therapy that has demonstrated effectiveness in managing pain. Our objective was to understand the feasibility and potential for an effect of a novel music app to address acute pain and anxiety in patients admitted to an emergency department observation unit. This prospective cohort study enrolled patients admitted to an emergency department observation unit with pain who had received orders for opioids. We gathered baseline pain and psychosocial characteristics including anxiety, sleep disturbance, and pain catastrophizing using validated questionnaires. Participants received a smartphone-based music intervention and listened to the music in either a supervised (research assistant-delivered music session 3 times during their stay) or unsupervised manner (music used ad lib by participant). The app collected premusic and postmusic pain and anxiety scores, and participants provided qualitative feedback regarding acceptability of operating the music intervention. We enrolled 81 participants and randomly assigned 38 to an unsupervised and 43 to a supervised group. Mean pain in both groups was 6.1 (1.8) out of a possible score of 10. A total of 43 (53%) reported previous use of music apps at home. We observed an overall modest but significant decrease in pain (mean difference -0.81, 95% CI -0.45 to -1.16) and anxiety (mean difference -0.72, 95% CI -0.33 to -1.12) after music sessions. Reduction of pain and anxiety varied substantially among participants. Individuals with higher baseline pain, catastrophizing (about pain), or anxiety reported greater relief. Changes in pain were correlated to changes in anxiety (Pearson ρ=0.3, P=.02) but did not vary between supervised and unsupervised groups. Upon conclusion of the study, 46/62 (74%) reported they liked the music intervention, 57/62 (92%) reported the app was easy to use, and 49/62 (79%) reported they would be willing to use the music intervention at home. A smartphone-based music intervention decreased pain and anxiety among patients in an emergency department observation unit, with no difference between supervised and unsupervised use. Individuals reporting the greatest reduction in pain after music sessions included those scoring highest on baseline assessment of catastrophic thinking, suggesting there may be specific patient populations that may benefit more from using music as an analgesic adjunct in the emergency department. Qualitative feedback suggested that this intervention was feasible and acceptable by emergency department patients.