Amiodarone and pulmonary toxicity in atrial fibrillation: a nationwide Israeli study.

BACKGROUND AND AIMS: Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used. METHODS: A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC. RESULTS: The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses. CONCLUSION: In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality.

Altered Serum Alpha1-Antitrypsin Protease Inhibition before and after Clinical Hematopoietic Stem Cell Transplantation: Association with Risk for Non-Relapse Mortality.

α1-Antitrypsin (AAT), an acute-phase reactant not unsimilar to C-reactive protein (CRP), is a serine protease inhibitor that harbors tissue-protective and immunomodulatory attributes. Its concentrations appropriately increase during conditions of extensive tissue injury, and it induces immune tolerance, in part, by inhibiting the enzymatic activity of the inflammatory serine protease, proteinase 3 (PR3). Typically administered to patients with genetic AAT deficiency, AAT treatment was recently shown to improve outcomes in patients with steroid-refractory graft-versus-host disease (GVHD). GVHD represents a grave outcome of allogeneic hematopoietic stem cell transplantation (HSCT), a potentially curative intervention for hematological diseases. The procedure requires radio/chemotherapy conditioning of the prospective marrow recipient, a cytotoxic process that causes vast tissue injury and, in some formats, interferes with liver production of AAT. To date, changes in the functional profile of AAT during allogeneic HSCT, and during the cytotoxic intervention that precedes HSCT, are unknown. The present study followed 53 patients scheduled for allogeneic HSCT (trial registration NCT03188601). Serum samples were tested before and after HSCT for AAT and CRP levels and for intrinsic anti-proteolytic activity. The ex vivo response to clinical-grade AAT was tested on circulating patient leukocytes and on a human epithelial cell line treated with patient sera in a gap closure assay. According to the ex vivo experiments, circulating leukocytes responded to AAT with a favorable immune-regulated profile, and epithelial gap closure was enhanced by AAT in sera from GVHD-free patients but not in sera from patients who developed GVHD. According to serum collected prior to HSCT, non-relapse mortality was reliably predicted by combining three components: AAT and CRP levels and serum anti-proteolytic activity. Taken together, HSCT outcomes are significantly affected by the anti-proteolytic function of circulating AAT, supporting early AAT augmentation therapy for allogeneic HSCT patients.

Does training make a difference? Proficiency training in transfusion guidelines and its effect on red blood cell administration.

BACKGROUND: Packed red blood cell (RBC) transfusion is a very common and frequently lifesaving therapeutic intervention, but a liberal transfusion policy may be associated with inferior patient outcomes. Various guidelines have been proposed to reduce the rate of unnecessary RBC transfusions. However, physicians' proficiency in such guidelines and the effect of training on RBC administration remain unknown. METHODS: We performed a questionnaire-based assessment of physicians' knowledge of the guidelines in a tertiary hospital in Israel, followed by an analysis of RBC administration six months before and six months after training was delivered. RESULTS: The level of proficiency was higher among Israeli university graduates (Odds Ratio [OR] 2.59, p-value = 0.02), internists (OR 2.8, p-value = 0.02), and physicians beyond the step-one residency exam (OR 3.08, p-value = 0.02). There was no significant effect of training on the rates of RBC administration (incidence rate ratio [IRR] = 0.96 [CI 95% 0.81-1.14], p-value = 0.655). CONCLUSION: Educational intervention alone is an ineffective means of reducing the rates of RBC administration. A more complex approach is required to prevent unnecessary RBC transfusions.

Comparison between diffuse and partial involvement of thoracic lymph nodes on the outcome of sarcoidosis patients.

BACKGROUND AND AIM: Sarcoidosis is a systemic disease of unknown etiology with diverse clinical manifestations. Disease may resolve spontaneously or require immunosuppression to control progression. Currently, there is no predictive model to direct treatment, and management is guided by symptoms and functional impairment. This study examines the association between biopsy features and prognosis. METHODS: This is a retrospective population-based cohort study. New cases of biopsy-proven sarcoidosis were divided into two groups: those with diffuse thoracic lymph nodes (TLN) involvement, versus partial TLN involvement (Defined as Non-necrotizing granuloma (NNG) found in some but not all sampled TLN). We compared outcomes one year after diagnosis. We assessed the need for immunosuppression, the number of hospitalizations, and lung function deterioration. RESULTS: 77 cases were included in the final analysis. 48.1% demonstrated extensive TLN involvement, and 51.9% demonstrated partial or non-involvement of sampled TLN. The partial positive group had a more aggressive disease, reflected by a significantly higher need for steroid therapy in the first year after diagnosis (45.0% vs. 18.9% p=0.015). The number of hospitalizations and lung functions were not significantly different between groups. CONCLUSIONS: Our findings demonstrate a significantly increased need for steroidal therapy among sarcoidosis patients with a partial positivity of TLN. These findings suggest that the degree of TLN involvement can help predict worse outcome and guide therapeutic decisions.

Clinician Risk Tolerance and Rates of Admission From the Emergency Department.

Importance: Much remains unknown about the extent of and factors that influence clinician-level variation in rates of admission from the emergency department (ED). In particular, emergency clinician risk tolerance is a potentially important attribute, but it is not well defined in terms of its association with the decision to admit. Objective: To further characterize this variation in rates of admission from the ED and to determine whether clinician risk attitudes are associated with the propensity to admit. Design, Setting, and Participants: In this observational cohort study, data were analyzed from the Massachusetts All Payer Claims Database to identify all ED visits from October 2015 through December 2017 with any form of commercial insurance or Medicaid. ED visits were then linked to treating clinicians and their risk tolerance scores obtained in a separate statewide survey to examine the association between risk tolerance and the decision to admit. Statistical analysis was performed from 2022 to 2023. Main Outcomes and Measures: The ratio between observed and projected admission rates was computed, controlling for hospital, and then plotted against the projected admission rates to find the extent of variation. Pearson correlation coefficients were then used to examine the association between the mean projected rate of admission and the difference between actual and projected rates of admission. The consistency of clinician admission practices across a range of the most common conditions resulting in admission were then assessed to understand whether admission decisions were consistent across different conditions. Finally, an assessment was made as to whether the extent of deviation from the expected admission rates at an individual level was associated with clinician risk tolerance. Results: The study sample included 392 676 ED visits seen by 691 emergency clinicians. Among patients seen for ED visits, 221 077 (56.3%) were female, and 236 783 (60.3%) were 45 years of age or older; 178 890 visits (46.5%) were for patients insured by Medicaid, 96 947 (25.2%) were for those with commercial insurance, 71 171 (18.5%) were Medicare Part B or Medicare Advantage, and the remaining 37 702 (9.8%) were other insurance category. Of the 691 clinicians, 429 (62.6%) were male; mean (SD) age was 46.5 (9.8) years; and 72 (10.4%) were Asian, 13 (1.9%) were Black, 577 (83.5%) were White, and 29 (4.2%) were other race. Admission rates across the clinicians included ranged from 36.3% at the 25th percentile to 48.0% at the 75th percentile (median, 42.1%). Overall, there was substantial variation in admission rates across clinicians; physicians were just as likely to overadmit or underadmit across the range of projected rates of admission (Pearson correlation coefficient, 0.046 [P = .23]). There also was weak consistency in admission rates across the most common clinical conditions, with intraclass correlations ranging from 0.09 (95% CI, 0.02-0.17) for genitourinary/syncope to 0.48 (95% CI, 0.42-0.53) for cardiac/syncope. Greater clinician risk tolerance (as measured by the Risk Tolerance Scale) was associated with a statistically significant tendency to admit less than the projected admission rate (coefficient, -0.09 [P = .04]). The other scales studied revealed no significant associations. Conclusions and Relevance: In this cohort study of ED visits from Massachusetts, there was statistically significant variation between ED clinicians in admission rates and little consistency in admission tendencies across different conditions. Admission tendencies were minimally associated with clinician innate risk tolerance as assessed by this study's measures; further research relying on a broad range of measures of risk tolerance is needed to better understand the role of clinician attitudes toward risk in explaining practice patterns and to identify additional factors that may be associated with variation at the clinician level.

A Comparison of Online Self-Training and Standard Bedside Training in Lung Ultrasonography for Medical Students.

PURPOSE: Point-of-care ultrasonography (POCUS) is increasingly integrated into medical education. Traditionally taught at the bedside using a hands-on approach, POCUS is limited by cost, time, faculty availability, and access to POCUS resources. With the recent transition to digitalization in medical education, the authors compare lung POCUS performance and pathology identification among medical students to examine whether using an online, self-learning lung POCUS module is noninferior to traditional bedside, faculty-led lung POCUS training. METHOD: This study assessed the performance of 51 medical students from August to October 2021 on an elearning lung POCUS course with traditional bedside training and no training. POCUS students were scored on use of a simulator to identify pathologies, ability to identify lung ultrasonographic pathological clips, and scanning technique. RESULTS: The elearning group had a significantly higher median (interquartile range [IQR]) total test score (15/18 [10.5-16] vs. 12/18 [9-13]; P = .03) and scanning technique score (5/5 [4-5] vs. 4/5 [3-4]; P = .03) compared with the standard curriculum group. The median (IQR) accuracy in the clip segment of the examination was 7.5 of 10 (4-9) in the self-learning group and 6 of 10 (4-7) in the standard curriculum group ( P = .18). The median (IQR) grade on the simulator segment of the examination was 2 of 3 (2-3) in the self-learning group and 2 of 3 (1-2) in the standard curriculum group ( P = .06). CONCLUSIONS: This study suggests that self-directed elearning of lung POCUS is at least noninferior to bedside teaching and possibly even a superior method of learning lung POCUS. This teaching method POCUS is feasible for medical students to learn lung ultrasonography and has potential to complement or augment the traditional learning process or eliminate or lessen the requirement for bedside teaching by reaching a larger audience while minimizing costs and human resources.

The Association between Varicella Vaccination and Herpes Zoster in Children: A Semi-National Retrospective Study.

Varicella vaccination in children has been performed worldwide in recent years. Despite established effectiveness, many countries still do not routinely vaccinate children against varicella, probably due to concerns about complications, such as herpes zoster infection. We aimed to compare the herpes zoster incidence in children before and after implementing the mandatory varicella vaccine in Israel in 2008. As a secondary aim, we characterized several parameters, including age, sex, and ethnic sector among herpes zoster cases, and we evaluated the complication rate to identify data relevant to the immunization status of the pediatric population. A retrospective study was conducted between 2000 and 2021, including patients aged 0-18 years old in a large cohort in southern Israel. A time series analysis and complication rates evaluations were performed in the pre- and post-vaccination eras. A total of 109.24 herpes zoster cases per 100,000 population per year were diagnosed between 2000 and 2007 (pre-vaccination era), compared to 354.71 herpes zoster cases per 100,000 population per year diagnosed between 2008 and 2021 (post-vaccination era) (p < 0.001). No change in the complication rate was documented. Thus, we concluded that there is an association between the varicella vaccine implementation program and the increase in the rate of herpes-zoster occurrence without a concurrent negative contribution to herpes zoster-related morbidity.

Correlation between kinetic and kinematic measures, clinical tests and subjective self-evaluation questionnaires of the affected upper limb in people after stroke.

Introduction: Assessment of stroke recovery should include multiple sources of information in order to obtain a complete understanding of the individual's rehabilitation progress. Self-evaluation questionnaires' scores do not always correspond to the scores of commonly used clinical evaluation tools. The purpose of this study was to assess the relationship between self-evaluation questionnaires, clinical tests, and kinematic and kinetic analyses of the affected upper limb after stroke, and to determine the correlation between these measures and self-reported general function 2-4 years after the stroke. Methods: Twenty-six subjects recovering from stroke were included in the study. Spearman's correlation coefficient was used to measure the correlation between Stroke Impact Scale (SIS), Motor activity Log (MAL), Fugl-Meyer Assessment (FMA) and Action Reach Arm Test (ARAT) scores, and kinematic and kinetic analyses. A logistic regression was used to assess the extent to which these measures may predict the participants' functional self-reported status 2-4 years post stroke. Results: Sections regarding hand function, hand force and general ADL of the self-evaluation questionnaires correlated with kinematic variables. However, only questionnaires that focus on hand function correlated with clinical tests. Mean and maximal hand velocity had the strongest correlations with self-evaluation questionnaires and with the clinical tests, more than other kinematic variables. Self-evaluation questionnaires and clinical tests were found to be correlated with hand kinetic metrics force-to-time ratio and number of force peaks. SIS hand force domain, mean velocity and maximal velocity predicted self-reported general function 2-4 years after the stroke. Conclusion: Self-evaluation questionnaires should be considered for wider use in the clinical evaluation of a patient's stroke recovery, since they add important information on the individual's functional status, which is not reflected in the clinical tests.

Corrigendum: Correlation between kinetic and kinematic measures, clinical tests and subjective self-evaluation questionnaires of the affected upper limb in people after stroke.

[This corrects the article DOI: 10.3389/fnins.2023.1264513.].

Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2.

Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections.

Lessons Learned from the Development and Implementation of Virtual and Telehealth Interprofessional Educational Clinics.

PURPOSE: The Interprofessional Educational (IPE) Clinic at Duke is a clinical experience that has allowed an interprofessional team, including health professions students, to care for patients in the emergency department (ED) since 2015. COVID-19 presented fundamental challenges to the structure of this experience, such as student restrictions on attending clinical experiences and limitations on the number of providers in a patient room, which necessitated a transition from face-to-face encounters to virtual ones. MATERIALS AND METHODS: As a result, two virtual experiences were implemented; one was based in the ED with in-person faculty and patients with virtual learners and one staffed by ambulatory providers engaging in telehealth clinics. These experiences sought to provide an interprofessional clinical experience for students while following appropriate safety guidelines. Surveys were distributed to students post-clinic to gather student demographics and their feedback regarding the experience. Additionally, faculty preceptors provided insight into the experience, especially regarding logistics and infrastructure. RESULTS: The virtual experiences successfully allowed teams of students to participate remotely in aspects of care including history taking, physical assessments, and medical decision-making. Additionally, the virtual care team structure allowed for senior students to mentor junior learners and for faculty members to provide point of care feedback. Students gained practical experience in telehealth that included logistics and challenges of providing virtual care and appreciating how technological barriers such as lack of access to internet-connected devices can be a source of disparity. CONCLUSION: The COVID-19 pandemic required the reconfiguration of an in-person clinical experience to a virtual experience and this pivot was well received by students and faculty. The lessons learned can be generalizable to other professional schools who may be seeking to develop an interprofessional clinical experience and are exploring telehealth options.

Attitudes toward risk among emergency physicians and advanced practice clinicians in Massachusetts.

OBJECTIVE: Risk aversion is a personality trait influential to decision making in medicine. Little is known about how emergency department (ED) clinicians differ in their attitudes toward risk taking. METHODS: We conducted a cross-sectional survey of practicing ED clinicians (physicians and advanced practice clinicians [APCs]) in Massachusetts using the following 4 existing validated scales: the Risk-Taking Scale (RTS), Stress from Uncertainty Scale (SUS), the Fear of Malpractice Scale (FMS), and the Need for (Cognitive) Closure Scale (NCC). We used Cronbach's α to assess the reliability of each scale and performed multivariable linear regressions to analyze the association between the score for each scale and clinician characteristics. RESULTS: Of 1458 ED clinicians recruited for participation, 1116 (76.5%) responded from 93% of acute care hospitals in Massachusetts. Each of the 4 scales demonstrated high internal consistency reliability with Cronbach's αs ranging from 0.76 to 0.92. The 4 scales also were moderately correlated with one another (0.08 to 0.54; all P < 0.05). The multivariable results demonstrated differences between physicians and APCs, with physicians showing a greater tolerance for risk or uncertainty (NCC difference, -3.58 [95% confidence interval, CI, -5.26 to -1.90]; SUS difference, -3.14 [95% CI: -4.99 to -1.29]) and a higher concern about malpractice (FMS difference, 1.14 [95% CI, 0.11-2.17]). Differences were also observed based on clinician age (a proxy for years of experience), with greater age associated with greater tolerance of risk or uncertainty (age older than 50 years compared with age 35 years and younger; NCC difference, -2.84 [95% CI, -4.69 to -1.00]; SUS difference, -4.71 [95% CI, -6,74 to -2.68]) and less concern about malpractice (FMS difference, -3.19 [95% CI, -4.31 to -2.06]). There were no appreciable differences based on sex, and there were no consistent associations between scale scores and the practice and payment characteristics assessed. CONCLUSION: We found that risk attitudes of ED clinicians were associated with type of training (physician vs APC) and age (experience). These differences suggest one possible explanation for the observed differences in decision making.

The Impact of Racial Bias in Patient Care and Medical Education: Let's Focus on the Educator.

Introduction: Racial bias in health care is well documented. Research shows the presence of racial bias among health care providers. There is a paucity of workshops focused on racial bias effects in health professions educators. Method: Two to three workshops were delivered to a diverse group of clinical educators from three programs at a major academic institution. Each workshop included a brief multimedia presentation followed by a facilitated group discussion. Participants completed the online Implicit Association Test (IAT), a baseline demographic questionnaire, and a brief post-then-pre questionnaire. Results: Twenty-four faculty participated in the study (six physicians, eight nurse practitioners, 10 physician assistants). Nineteen (90%) were women, 18 (86%) were White, nine (43%) had more than 10 years of experience as educators, and seven (35%) had previously participated in a biases program. Seventeen completed the IAT. Sixteen educators agreed or strongly agreed that bias has a significant impact on patients' outcomes at the end of the workshop compared to 17 before the workshop. Seventeen educators agreed or strongly agreed that recognizing their own racial bias would positively alter their teaching practice after the workshop compared to 15 before the workshop. Discussion: This series of workshops was created to fill a gap regarding the impact of racial bias on patient outcomes, health disparities, and health professions education. The impact of racial bias in health professions education and the long-term impact of awareness and knowledge of racial bias in education are areas needing further evaluation.

A Tablet-Based Educational Tool: Toward More Comprehensive Pediatric Patient Education.

There is a paucity of data on the impact of mobile technology on physician-led education in the pediatric population. We performed a prospective pilot study in a pediatric diabetes clinic to evaluate the impact of tablet-based patient education. A total of 106 patients and caregivers completed postclinic surveys, 64 (60%) in the intervention group and 42 (40%) in the control group. The majority of the intervention group patients (86%) liked tablet use and felt it was better or similar (99%) to baseline. Moreover, a majority receiving tablet-based education perceived an increase in diabetes knowledge (57%) compared with baseline (39%), though the difference did not reach statistical significance ( P = .059). Those who received tablet-based education felt they were educated on more diabetes-related topics. As the use of mobile technology in medicine grows, additional research is needed to compare mobile technology with traditional methods in providing education to the pediatric population.

Perspectives of Emergency Clinicians About Medical Errors Resulting in Patient Harm or Malpractice Litigation.

This cross-sectional study analyzes responses to a survey about medical error outcomes completed by emergency department attending physicians and advanced practice clinicians.

Factors in medical students' selection and ranking of combined medicine-pediatrics programs.

This survey of U.S. medical students applying to combined medicine-pediatrics programs explored the factors involved in deciding to apply to and ranking of these programs.