2-year Course Research Articles

A Case of Zoonotic Domestically Acquired Hansen Disease (Leprosy) in the State of Georgia

Introduction: Hansen Disease (HD) is an infection of the bacteria Mycobacterium leprae causing rash and anesthesia of the skin. It is endemic to many developing countries, where it is spread by direct contact. Zoonotic transmission through the 9-banded armadillo (Dasypus novemcinctus) has been documented in North America. HD is rare in the state of Georgia and most cases are from individuals travelling from HD endemic regions. Case Report: The patient developed red, infiltrated, anesthetic plaques covering 20% of her body. Fite staining revealed mycobacterial organisms suggesting lepromatous HD. The patient had no relevant history of travel or personal health history. The patient gardened outdoors in Southern Georgia. She knew armadillos were present in the area, but she did not have direct contact with one. The suspected mode of transmission was through feces of an infected armadillo in the soil. The patient is being treated with a 2-year course of rifampin, clofazimine, and dapsone, and reports improvement. Discussion: Domestically acquired HD is generally seen in other Southern states with greater armadillo populations. The range of the 9-banded armadillo is expanding, which potentially puts a greater area of the country at risk for exposure to HD. Therefore, increasing resources for treatment of HD is important. Conclusion: This case report presents a case of HD with indirect zoonotic transmission.

Helicopter emergency medical services in Iceland between 2018 and 2022-A retrospective study.

Helicopter emergency services (HEMS) are widely used to bring medical assistance to individuals that cannot be reached by other means or individuals that have time-critical medical conditions, such as chest pain, stroke or severe trauma. It is a very expensive resource whose use and importance depends on local conditions. The aim of this study was to describe flight and patient characteristics in all HEMS flights done in Iceland, a geographically isolated, mountainous and sparsely populated country, over a 5-year course. This retrospective study included all individuals requiring HEMS transportation in Iceland during 2018-2022. The electronic database of the Icelandic Coast Guard was used to identify the individuals and register flight data. Electronic databases from Landspitali and Akureyri hospitals were used to collect clinical variables. Descriptive statistics was applied. The average number of HEMS transports was 3.5/10,000 inhabitants and the median [IQR] activation time and flight times were 30 min [20-42] and 40 min [26-62] respectively. The vast majority of patients were transported to Landspitali Hospital in Reykjavik. More than half of the transports were due to trauma, the most common medical transports were due to chest pain or cardiac arrests. Advanced medical therapy was provided for 66 (10%) of individuals during primary transports, 157 (24%) of individuals were admitted to intensive care, 188 (28%) needed surgery and 53 (7.9%) needed a coronary angiography. In Iceland, the number of transports is lower but activation and flight times for HEMS flights are considerably longer than in other Nordic countries, likely due to geographical features and the structure of the service including utilizing helicopters both for HEMS and search and rescue operations. The transport times for some time-sensitive conditions are not within standards set by international studies and guidelines.

Surgical decompression in spinal Paget's disease: illustrative case.

Paget's disease of bone (PDB) is a common bone metabolic pathology in older adults, characterized by mixed osteolytic, osteoblastic, and quiescent periods. Surgical guidelines for PDB involving the spine are not well-defined and are reserved for cases refractory to medical treatments, typically bisphosphonates like zoledronic acid. This case study describes a 52-year-old male with PDB who presented with rapidly progressing myelopathy symptoms refractory to standard medical treatment, warranting surgical decompression. Surgical decompression and fusion, involving laminectomy with partial facetectomies, placement of pedicle screw instrumentation, and posterolateral arthrodesis spanning beyond the pathological segment, was performed. Follow-up visits indicated progressive improvement in symptoms and mobility, and imaging showed stable postsurgical changes with increased sclerosis in the affected vertebrae on a 2-year postsurgical course. This case underscores that PDB of the spine can transition from asymptomatic to significant impairment and demonstrates that surgical intervention can provide effective symptomatic relief in myelopathy secondary to PDB. The case contributes to the growing evidence of the effectiveness of surgical decompression in PDB involving the spine. https://thejns.org/doi/10.3171/CASE24203.

The Pre-service Teachers’ Perceptions of Integrated Teaching, Inquiry Learning, using ICT and Real-life Examples in Science Classes

The study was conducted as a case study to enhance pre-service science teachers’ readiness for integration, inquiry-based learning (IBL), the use of Information and Communication Technology (ICT), and the application of real-life examples during their teacher training courses. The objective of the research was to explore pre-service science teachers’ perceptions of integrated teaching, inquiry learning, and the use of ICT in science education, drawing on their experiences in teacher training. It also aimed to examine potential differences in their viewpoints and the evolution of their perceptions over time. A questionnaire was developed to gather insights from 50 pre-service science teachers regarding their views on the integration of science subjects before and after their 2-year teacher training courses. The collected data were analyzed using a qualitative approach with the QCAmap software, followed by a quantitative analysis utilizing the Microsoft Excel software. The findings revealed significant variances in perceptions among pre-service teachers based on the number of science subjects they studied during their training. Those who studied two or more subjects placed greater emphasis on the value of integration, IBL, ICT use, and real-life examples in science education, and exhibited more significant changes in their views throughout the 2 years of teacher training. Furthermore, the study found that nearly half of the pre-service teachers did not view IBL in science classes as crucial, and only about a quarter recognized the importance of ICT utilization.

Decision analysis for transplant candidates with primary myelofibrosis in the ruxolitinib era.

The recent progress with ruxolitinib treatment might improve quality-of-life as well as overall survival in patients with primary myelofibrosis (PMF). Therefore, the optimal timing of allogeneic hematopoietic cell transplantation (HCT) remains to be elucidated in the ruxolitinib era. We constructed a Markov model to simulate the 5-year clinical course of transplant candidates with PMF, and compared outcomes between immediate HCT and delayed HCT after ruxolitinib failure. Since older age was associated with an increased risk of mortality, we analyzed patients aged < 60 and ≥ 60 separately in subgroup analyses. The expected life years was consistently longer in delayed HCT after ruxolitinib failure regardless of patient age. Regarding quality-adjusted life years (QALYs), a baseline analysis showed that immediate HCT was inferior to delayed HCT after ruxolitinib failure (2.19 versus 2.26). In patients aged < 60, immediate HCT was equivalent to delayed HCT after ruxolitinib failure (2.31 versus 2.31). On the other hand, in patients aged ≥ 60, immediate HCT was inferior to delayed HCT after ruxolitinib failure (1.98 versus 2.21). A one-way sensitivity analysis showed that the utility of being alive without chronic graft-versus-host disease after immediate HCT was the most influential parameter for QALYs, and that a value higher than 0.836 could reverse the superiority of delayed HCT after ruxolitinib failure. As a result, delayed HCT after ruxolitinib failure is expected to be superior to immediate HCT, especially in patients aged ≥ 60, and is also a promising strategy even in those aged < 60.

LGG-16. BRAFV600K LOW-GRADE GLIOMA EMERGENCE DURING THERAPY FOR BRAFV600E HIGH-GRADE GLIOMA

Abstract BACKGROUND BRAFV600E mutations are prevalent in pediatric brain tumors, constituting 20% of low-grade and 5% of high-grade gliomas. Other single-nucleotide substitutions in BRAF are described in adult cancers but rarely in pediatric brain tumors. Our case sheds light on a unique scenario—a patient with a BRAF-mutated high-grade spinal glioma who later developed slowly progressive intracranial low-grade glioma, subsequently undergoing rapid high-grade transformation. METHODS Case Report RESULTS Our patient initially presented as a thirteen-year-old male with a two-month history of progressive bilateral hand weakness/paresthesias. Spine MRI revealed a fusiform expansile intramedullary neoplasm from C3-T2, brain MRI was negative. Biopsy showed an anaplastic astrocytoma with BRAFV600E mutation and MYC-N amplification. Initial treatment included proton radiation and a 2-year course of Dabrafenib/Trametinib, maintaining disease stability. After four months off therapy, he developed local progression, and re-staging brain MRI showed new cerebellar/supratentorial lesions. Dabrafenib/Trametinib was re-started until progression two years later. He developed hydrocephalus and underwent ETV and brain tumor biopsy, which revealed a low-grade glioma with BRAFV600K mutation. At this point, Dabrafenib/Trametinib continued for another 1.5 years; he exhibited slow progression of the brain tumors before a cerebellar lesion developed rapid progression. He had GTR of the rapid-growing lesion, and pathology reported a Grade 4 invasive astrocytoma harboring BRAFV600E, two VUS MTOR mutations, and MGMT promoter methylation. Current treatment involves radiation therapy concurrent with temozolomide. CONCLUSIONS While combinatorial Dabrafenib/Trametinib is effective in glioma therapy, resistance and progression challenges persist. Our case presents a unique manifestation—a patient with a spinal high-grade glioma with BRAFV600E who developed a secondary low-grade glioma with BRAFV600K in the brain, which, after several years, transformed into a high-grade glioma. Future research is crucial for comprehending the intricate role of BRAF mutations in pediatric gliomas, paving the way for improved patient outcomes.

Association of human leukocyte antigen (HLA) status with immune checkpoint inhibitor (ICI) pneumonitis in patients with non-small cell lung cancer (NSCLC).

8620 Background: Pneumonitis is a potentially serious complication occurring in 5-20% of lung cancer patients receiving ICI. The genetic risk factors for ICI pneumonitis are unclear. Given the association between HLA genetic variants and autoimmune diseases, we hypothesized that certain HLA genetic variants are associated with risk of ICI pneumonitis. Methods: Patients with advanced EGFR/ ALK wild type, PD-L1 tumor proportion score ≥50% NSCLC who received ICI were enrolled from year 2019 to 2022. Germline HLA typing was performed on buccal swab specimens using the Alltype Fastplex assay. Clinicopathological characteristics, treatment courses and survival outcomes were retrospectively collated. The primary endpoint was the correlation of common HLA variants (present in &gt;30% of subjects) to the risk of ICI pneumonitis. Results: 42 patients (all Chinese, 36 male, 33 current/former smokers) were enrolled. Median age was 71 years old (range 51-91). 34, 6, 1 and 1 patients had adenocarcinoma, NSCLC not otherwise specified, squamous cell carcinoma and large cell neuroendocrine carcinoma respectively. Majority (33/42, 79%) received pembrolizumab monotherapy while 9 (21%) patients received pembrolizumab plus chemotherapy. Median follow up time was 27.8 months. At data cutoff, 28 (67%) patients received ICI for more than 1 year and 10 (24%) patients stopped ICI after completion of 2-year course of treatment. Seven (17%) patients developed pneumonitis, of which 3 were grade 2 and 4 were grade 3 in severity. Median time to development of pneumonitis was 6.9 months (range 0.3-25.2). Demographic characteristics were similar between patients who did or did not experience pneumonitis. In the entire cohort, twenty-two (52%) patients harbored the class II DPB1*02 allele. This allele was significantly associated with development of ICI pneumonitis. All 7 patients who had ICI pneumonitis harbored the DPB1*02 allele. The incidence of pneumonitis in patients harboring the DPB1*02 allele was 32% compared to 0% in those without this allele (p=0.009). Patients who experienced pneumonitis had worse survival rates than those without (p=0.03), but expression of DPB1*02 allele was not associated with inferior survival outcomes. Conclusions: Our results suggested that expression of DPB1*02 allele may be associated with development of ICI pneumonitis. A larger case-control study is ongoing to validate this association. [Table: see text]

Real-World Effectiveness of Cladribine for Patients with Multiple Sclerosis: A Sicilian Multicentric Experience (Rewind Study).

Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS). The study aims to evaluate the effectiveness of cladribine in a real-world setting. This prospective real-world study consecutively screened all RRMS patients from seven different MS centers in Sicily (Italy) who completed the 2-year treatment course of cladribine tablets in the period between 11th March 2019 and 31st October 2021. Data about Expanded Disability Status Scale (EDSS), relapses, previous treatments, adverse events (AEs) and magnetic resonance imaging (MRI) were collected. Patients who were previously treated with other DMTs were further stratified into moderately active treatment (MAT) and highly active treatment (HAT) patients. A total of 217 patients (70% women, with a mean age of 38.4 ± 11.3 years) were enrolled. Fifty patients (23.0%) were naïve to treatment and 167 (77%) switched from other disease modifying therapies. After the second year of treatment, about 80% were EDSS progression free, 88% remained relapse-free at T24, and 48% of patients were MRI activity-free. Kaplan Meier analyses showed significant differences between MT and HAT in terms of time to first clinical relapse (HR: 2.43, IC 1.02- 5.76; p = 0.04), time to the first new T1-gadolinium enhancing lesion (HR: 3.43, IC 1.35-8.70; p = 0.009) and time to MRI worsening (HR: 2.42, IC 1.15-5.09; p = 0.02). This study confirmed that cladribine is an effective treatment for MS, particularly in naïve patients and those who have switched from MATs.

Nurse Educators, Clinical Nurses and Students’ Knowledge, Attitude and Practice towards Nursing Education in Bhutan

Abstract Background: In Bhutan, the Health School started in 1972 providing a 2-year certificate course for community health workers, assistant nurses and assistant technicians. In 1982, the Diploma course for nurses commenced and was assisted by the RAK College of Nursing Faculty, New Delhi, India, in formalising the curriculum and also carried out the evaluation of the first batch of nursing students. Objective: The study assesses the knowledge, attitude and practice (KAP) of nurse educators (NEs), clinical nurses and students undergoing the Diploma in Nursing and Midwifery training towards nursing education in Bhutan. Methods: The methodology was a quantitative study using a self-administered questionnaire. The first section had demographic data, and the second had questions on KAP. The participants were NEs, students and clinical nurses. The study was done in the nursing institute, the national hospital and the district hospitals. The instrument, i.e. questionnaire, had a five-point Likert scale from ‘excellent, good, fair, poor, to very poor’ Results: In the results, students rated the KAP of NEs and clinical nurses as ‘good’. On the contrary, the attitude of students towards ‘gaining knowledge from the clinical area’ and their ‘eagerness to learn nursing’ are rated ‘fair’ Conclusion: The KAP provides a detailed view of the status of nursing education, and the data obtained from the study provide strong baseline information for nursing education in the future.

Abstract PO5-01-12: Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens

Abstract Late recurrence of breast cancer remains a significant challenge in patient management. Despite the established efficacy of hormone therapy, factors influencing late recurrence and the impact of different hormone therapy regimens on this outcome are not yet fully understood. This study aims to investigate the key determinants contributing to late recurrence within the context of different hormone therapy regimens. This study is a retrospective analysis of medical records from two institutions between 1988 and 2018, specifically examining patients who had HR-receptor positive breast cancer who underwent surgery and completed a 5-year course of standard hormone therapy. Primary endpoint is to identify the demographic, clinical and pathologic factors as associated with late recurrence. Out of 1929 eligible patients, 49.6% (956) received Tamoxifen (TMX), 37.6% (726) received Aromatase inhibitors (AI), and 12.8% (247) switched between regimens (TMX to AI or AI to TMX). Median follow-up was 12.1 years (3.75 - 21.41 years). During this period, all-type recurrence (ATR) occurred in 9.3% of all patients, with higher rates in the TMX recipients (12.2%). Locoregional and contralateral recurrence were identified in 10.6% of TMX recipients, 6.5% of patients who switched regimens, and 5% of AI recipients. In all patients, 5.4% were diagnosed with distant metastasis, with slightly higher rates in the TMX recipients (6.4%). Multiple sites in the bone, lung, liver and brain (34.3%) was the most prevalent location of distant metastasis (DM), followed by soft tissue (20%), liver (16.2%), bone (10.5%), lung (8.6%), and other locations. Significant differences in recurrence-free survival (RFS) were observed between hormone therapy groups (p=0.004, log-rank test). Mean overall RFS was 20.4 years (95% C.I. 20.1-20.9 years). TMX recipients had a mean RFS of 19.8 years, AI recipients had a mean RFS of 18.3 years and those who switched regimens had a mean RFS of 21.9 years. Further analysis showed premenopausal patients who switched regimens had higher RFS (p=0.014). No significant difference in RFS was seen between premenopausal patients receiving AI or Tamoxifen, or amongst post-menopausal patients with different hormone therapy regimens. No significant difference in distant metastasis-free survival (DMFS) was observed between hormone therapy groups (p=0.442). Mean overall DMFS was 21.5 years (95% C.I. 21.2 - 21.8 years), with TMX patients 21.1 years, AI patients at 18.6 years, and those who switched regimens at 21.4 years. Sub-analyses of DMFS in pre and postmenopausal patients with different hormone therapy regimens showed no significant differences. Multivariate analysis showed tumor size ≤ 2cm (p= 0.0001) and negative axillary node involvement (p= 0.0001) significantly decreased odds of developing late all-type recurrence (ATR) in TMX recipients. In patients who switched regimens, Her2 positivity (p=0.04) significantly decreased the odds of late ATR. In AI recipients, not undergoing axillary operation (p = 0.008) significantly increased the odds of late ATR. For TMX recipients, negative axillary node involvement (p=0.004), tumor size ≤ 2cm (p=0.03), and undergoing mastectomy (p=0.02) significantly decreased odds of distant metastasis (DM). Among patients who switched regimens, adjuvant anti-Her2 therapy (p=0.02) significantly decreased odds of DM. For AI recipients, high PR score (p=0.02) and undergoing sentinel lymph node biopsy significantly decreased odds of DM, while age &amp;lt; 50 years significantly increased odds of developing DM. These findings emphasize the significance of the relationship between hormone therapy regimens and factors affecting late recurrence, thereby providing valuable insights for clinical decision-making. Risk stratification based on identified factors can help in identifying patients at higher risk of late recurrence allowing for more intensive surveillance and potentially early intervention. Univariate (Chi-square, Logistic Regression) and Multivariate Analysis (Logistic Regression) for Clinicopathologic factors associated with all-type recurrence and distant metastasis after surgery and completion of 5-years endocrine therapy Table. a. LN lymph node b. SLNB, Sentinel lymph node biopsy c. ALND, Axillary lymph node dissection d. Cutoff values of Ki67 14% in KUAH and 10%in SNUH e. ER and PR cutoff value is 10% f. UV, Univariate analysis, MV multivariate analysis, O.R. Odds Ratio, C.I. Confidence Interval Citation Format: Mary Rose Mendoza, Eun-Shin Lee. Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-12.

Abstract PO2-17-05: Pharmacy fills but not baseline distress or other clinical factors can identify those at high risk for early adjuvant endocrine therapy discontinuation

Abstract Background Completion of the recommended 5-10 year course of adjuvant endocrine therapy (AET) course is low, and few risk factors for discontinuation have been identified. We examined factors associated with early AET discontinuation in a large cohort with patient-reported outcomes (PROs) and other measures routinely used in clinical care at four sites within an academic health system's multidisciplinary cancer center. Methods We examined postmenopausal women with stage I-III hormone-receptor positive breast cancer identified using the registry at an academic multidisciplinary cancer center 2014-19 who received a prescription for AET, and followed them for up to 5 years. Breast cancer extent of disease and treatments, Elixhauser comorbidity index, medication number and sociodemographic characteristics (age, race/ethnicity, insurance, area deprivation index of zip code of residence) were abstracted from the electronic health record (EHR). PRO measures included the Distress Thermometer (DT, scored 0-10) and its associated problem list (39 yes/no questions), and the Patient Health Questionnaire-9 (depression), all administered routinely as part of clinical care between diagnosis date and start of AET. If &amp;gt;1 PRO performed during that time, the measure closest to AET start was used. DT was dichotomized using the clinically accepted score of 4 as the threshold for severe distress, as was Patient Health Questionnaire-9 (PHQ-9) depression ( &amp;gt;5). AET prescription information included both prescription date from the EHR, and prescription fills assessed using an all-payer pharmacy data source. AET was defined as discontinued (d/c) when no prescription had been filled at any pharmacy for at least 90 days. We used nonparametric hypotheses test for two-samples (d/c vs. no d/c) as well as Kaplan-Meier product-limit time-to-event analyses with censoring for recurrence, death, or change of provider, and advanced machine learning to examine the association of these variables with discontinuation prior to five years. 54 curated covariates were examined in all, corresponding to a Bonferroni statistical significance p-value threshold of 0.001 to control type I error. Sensitivity analyses were performed to 1)use alternative date of DT (closest to diagnosis date) and 2)to examine d/c defined as 180 days. Results Among the cohort of 985 women (74% stage I, 25% Elixhauser comorbidity score &amp;gt;2), 36.9% had a DT &amp;gt;4, and 6.7% a PHQ-9 &amp;gt;5. The cohort had a median followup time of 954 days, and during followup 291 women ( 29.5) % discontinued before completion of the 5-year course or censoring for death, change to a provider outside the system or study end date in 2021. Over 40% of women who stopped filling prescriptions never had their prescriptions discontinued by their physician in the EHR. None of the examined variables including those for Distress and PL, PHQ-9 and measures of extent of disease, cancer treatments, medication number and sociodemographic characteristics were associated with early discontinuation. Results were similar in analyses using the DT date closest to diagnosis or a 180-day prescription fill gap. We also used advanced machine learning with respect to time to event discontinuation had similar results. Conclusions. Clinically available EHR data including two PRO measures were not reliable predictors of early discontinuation. However, many women who had discontinued still had orders for AET in the EHR, suggesting that their physicians were unaware that they had stopped filling prescriptions. Future work should examine whether routine monitoring of prescription fills might be enlisted to identify these women and assist with education, supportive care or other assistance to restart. Citation Format: Joan Neuner, Rodney Sparapani, Jacob Tiegs, Vaia Makris, Melinda Stolley, Sailaja Kamaraju, Bradley Crotty, Kathryn Flynn. Pharmacy fills but not baseline distress or other clinical factors can identify those at high risk for early adjuvant endocrine therapy discontinuation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-05.

Prospective 2-Year Course and Predictors of Outcome in Avoidant/Restrictive Food Intake Disorder

To evaluate the 2-year course and outcomes of full and subthreshold avoidant/restrictive food intake disorder (ARFID) in youth aged 9 to 23 at baseline using a prospective longitudinal design to characterize the remission and persistence of ARFID, evaluate diagnostic crossover, and identify predictors of outcome. Greater severity in each ARFID profile-sensory sensitivity, fear of aversive consequences, and lack of interest-was hypothesized to predict greater likelihood of illness persistence, controlling for age, sex, body mass index percentile, ARFID treatment status, and baseline diagnosis. Participants (N= 100; age range, 9-23 years; 49% female; 91% White) were followed over 2 years. The Pica, ARFID, and Rumination Disorder Interview was used across 3 time points (baseline, year 1, year 2) to measure the severity of each ARFID profile and evaluate illness persistence or remission, and the Eating Disorder Assessment for DSM-5 was used to evaluate diagnostic crossover. Across the 2-year follow-up period, half the participants persisted with their original diagnosis, and 3% of participants experienced a diagnostic shift to anorexia nervosa. Greater severity in the sensory sensitivity and lack of interest profiles was associated with higher likelihood of ARFID persistence at year 1 only; greater severity in the fear of aversive consequences profile was associated with higher likelihood of ARFID remission at year 2 only. Findings underscore the distinctiveness of ARFID from other eating disorders and emphasize its persistence over 2 years. Results also highlight the predictive validity and prognostic value of ARFID profiles (ie, sensory sensitivity, fear of aversive consequences, lack of interest).

Does Medical Curriculum Impact on Empathy? A Longitudinal Study in a Sample of Undergraduate Medical Students

Empathy in medical students is receiving increasing attention as it is fundamental to build and develop a functional patient-physician relationship. When looking at its determinants, demographic and academic factors seem to concur in shaping empathy in this population. Although data show strong gender differences and changes in empathy throughout medical school, it is not clear the direction of these changes and whether gender and curriculum features modulate them. This longitudinal study examined changes in empathy and explored gender differences throughout the medical school. Four consecutive cohorts of Italian medical students (N = 336) completed the Jefferson Scale of Empathy – Student (JSE-S) and the Interpersonal Reactivity Index (IRI) in their second year of study (before any clinical clerkship and communication skills courses) and fifth year of study (after a 2-year clinical clerkship and communication skills courses). Analysis of variance for repeated-measures revealed that, beyond the effect of gender, JSE-S total score and IRI Perspective Taking increased, whereas IRI Personal Distress and IRI Fantasy significantly decreased throughout medical school. No significant change in IRI Empathic Concern emerged over time. Student’s t-tests showed that female students displayed significantly higher mean scores than their male counterparts for all empathy measures in both their second and fifth years of medical training. The findings suggest that the medical curriculum affects self-reported empathy dimensions among undergraduate medical students. Further research is needed to deepen the understanding of the educational factors that promote the changes in empathy levels during medical training.

A new custom-made bivalve brace for pectus carinatum in children and adolescents: preliminary promising experience of 140 patients from a tertiary center.

International research suggests that poor patient compliance is the main cause of tutor failures in the context of potential novel orthopedic bivalve braces for conservative treatment of pectus carinatum. Our entire experimental study is based on the hypothesis that a rigid bivalve brace that patients can accept could solve the main problem associated with the conservative approach-poor compliance. The hypothesis was to reduce the thickness and weight of the classic bivalve brace to ensure concealment and make it sustainable enough to be worn several hours a day without compromising its therapeutic efficacy. The research was conducted from January 2020 to December 2022 to ensure follow-up of all participants for at least 6 months. In 36 months, 140 patients with pectus carinatum were assessed and conservatively treated with the studied guardian to analyze the therapeutic efficacy of the bivalve brace and patient compliance. From the initial visit, the parents and patient were informed that this is a 2-year therapeutic course during which the bivalve brace should be worn at least 23 h a day (with 1 h of abstinence per day for routine personal hygiene practices). Compliance is the key to therapy success, and the duration of treatment depends on patient adherence. The exceptional effectiveness of the experimental brace was confirmed by both the questionnaire from the patients (with an average satisfaction rate of 8.9/10) and an assessment of the therapy's results by a properly selected medical committee (with a VAS scale satisfaction of 7.2/10 for symmetric forms and 7.1/10 for asymmetric ones). In conclusion, the analyzed data confirmed the research hypotheses. First, none of the 140 patients had cardiovascular diseases directly related to their condition, confirming that pectus carinatum is a pathology of a purely aesthetic nature. Second, a cheap, lightweight, and easily obscured brace significantly improved patient compliance. Along with this, the social relevance of the aesthetic aspect today may be an important factor in motivating the study cohort to adhere to therapy. In the past, esthetics and appearance were less relevant at the social level, which may have contributed to the high abandonment and reduced compliance rates of the many studies in the literature.

Therapeutic choices and disease activity after 2 years of treatment with cladribine: An Italian multicenter study (CladStop).

Cladribine tablets, a purine analogue antimetabolite, offer a unique treatment regimen, involving short courses at the start of the first and second year, with no further treatment needed in years 3 and 4. However, comprehensive evidence regarding patient outcomes beyond the initial 24 months of cladribine treatment is limited. This retrospective, multicenter study enrolled 204 patients with multiple sclerosis who had completed the 2-year course of cladribine treatment. The primary outcomes were therapeutic choices and clinical disease activity assessed by annualized relapse rate after the 2-year treatment course. A total of 204 patients were enrolled; most patients (75.4%) did not initiate new treatments in the 12 months postcladribine. The study found a significant reduction in annualized relapse rate at the 12-month follow-up after cladribine completion compared to the year prior to starting therapy (0.07 ± 0.25 vs. 0.82 ± 0.80, p < 0.001). Furthermore, patients with relapses during cladribine treatment were more likely to start new therapies, whereas older patients were less likely. The safety profile of cladribine was favorable, with lymphopenia being the primary registered adverse event. This study provides insights into therapeutic choices and disease activity following cladribine treatment. It highlights cladribine's effectiveness in reducing relapse rates and disability progression, reaffirming its favorable safety profile. Real-world data, aligned with previous reports, draw attention to ocrelizumab and natalizumab as common choices after cladribine. However, larger, prospective studies for validation and a more comprehensive understanding of cladribine's long-term impact are necessary.

Two-year course of walking adaptability in persons living with late effects of polio.

To evaluate the 2-year course of walking adaptability in persons with late effects of polio. Prospective cohort study. A total of 48 persons with late effects of polio (69% female, mean age 63.1 years) with a fall history and/or fear of falling. Walking adaptability (i.e. variable target-stepping and reactive obstacle-avoidance) was assessed on an interactive treadmill at baseline, 1 year and 2 years. Further, leg-muscle strength and balance were assessed at baseline. The course of walking adaptability was analysed with linear mixed models. Based on median values, subgroups were defined for low vs high baseline walking-adaptability and for clinical characteristics. Tme by subgroup interactions were analysed. Variable target-stepping and reactive obstacle-avoidance did not change (p > 0.285). Reactive obstacle-avoidance improved for persons with a high balance score at baseline (p = 0.037), but not for those with lower scores (p = 0.531). No other time by subgroup interactions were found (p > 0.126). Walking adaptability did not change in persons with late effects of polio over 2 years, and walking adaptability course did not differ between subgroups stratified for walking adaptability determinants, except for balance. Since falls are a major problem among persons with late effects of polio, future studies should investigate whether walking adaptability declines over a longer time and which persons are most at risk.

Mapping competency in public health training – experience of the Europubhealth consortium

BackgroundPublic health education aims at producing a competent workforce. The WHO-ASPHER framework proposes a set of relevant public health competencies organised in 10 sections (e.g. science practice, leadership, law policies and ethics etc). As part of the Europubhealth (EPH) consortium, eight universities collaborate for the delivery of a 2-year international public health master course. The training pathway includes a first “foundation” year, with a choice of four options (components), and a second “specialisation” year with a choice of seven components. In 2020, EPH consortium decided to use the WHO-ASPHER framework in order to map the competencies addressed and the level of proficiency targeted by each component of its master course.MethodsAn 84-item questionnaire covering the whole WHO-ASPHER framework was sent to the 11 EPH component coordinators, asking them to rate the proficiency levels targeted at the end of their courses. Answers from each coordinator were summarised by calculating mean proficiency levels for each of the 10 competency sections. We used Bland & Altman plots to explore heterogeneity of answers and then calculated transformed scores to account for rating heterogeneity. We use tabulation and a heat map to explore patterns of proficiency levels across components.ResultsThere were differences in overall proficiency levels between years with, as expected, higher scores in year two. Year one components reached medium to high proficiency scores for the sections “science practice”, “health promotion” and “communication” with scores ranging from 2.6 to 3 (on a 1-low to 4-high scale). When compared with year one on a heat-map, year two components displayed more contrasted profiles, typically aiming for high proficiency level (i.e. scores above 3.5) on 3 out of the 10 sections of competencies. Except for the “collaborations and partnership” section, the training pathways offered by the EPH master course seem to offer opportunities for a high proficiency level in all domains of competencies.ConclusionsThe mapping proved a useful exercise to identify strengths and complementarities among the EPH consortium. The results suggest that the EPH master course is coherent and offers students opportunities to gain proficiency in most competencies relevant to public health practice.

Similar and different? A cross-cultural comparison of the prevalence, course of and factors associated with suicidal thoughts and behaviors in first-episode psychosis in Chennai, India and Montreal, Canada.

Data from high-income countries (HICs) show a high risk of suicidal thoughts and behaviors (STBs) in first-episode psychosis (FEP). It is unknown, however, whether rates and associated factors differ in low- and middle-income countries (LMICs). We therefore aimed to compare the 2-year course of STBs and associated factors in persons with FEP treated in two similarly structured early intervention services in Chennai, India and Montreal, Canada. To ensure fit to the data that included persons without STBs and with varying STBs' severity, a hurdle model was conducted by site, including known predictors of STBs. The 2-year evolution of STBs was compared by site with mixed-effects ordered logistic regression. The study included 333 FEP patients (168 in Chennai, 165 in Montreal). A significant decrease in STBs was observed at both sites (OR = 0.87; 95% CI [0.84, 0.90]), with the greatest decline in the first 2 months of follow-up. Although three Chennai women died by suicide in the first 4 months (none in Montreal), Chennai patients had a lower risk of STBs over follow-up (OR = 0.44; 95% CI [0.23, 0.81]). Some factors (depression, history of suicide attempts) were consistently associated with STBs across contexts, while others (gender, history of suicidal ideation, relationship status) were associated at only one of the two sites. This is the first study to compare STBs in FEP between two distinct geo-sociocultural contexts (an HIC and an LMIC). At both sites, STBs reduced after treatment initiation, suggesting that early intervention reduces STBs across contexts. At both sites, for some patients, STBs persisted or first appeared during follow-up, indicating need for suicide prevention throughout follow-up. Our study demonstrates contextual variations in rates and factors associated with STBs. This has implications for tailoring suicide prevention and makes the case for more research on STBs in FEP in diverse contexts.

The p factor outweighs the specific internalizing factor in predicting recurrences of adolescent depression.

The early prediction of adolescent depression recurrence poses a significant challenge in the field. This study aims to investigate and compare the abilities of the general psychopathology factor (p) and the specific internalizing factor, in predicting depression recurrence over a 2-year course, as well as identifying remitted depressed adolescents from healthy adolescents. Longitudinal changes of these two factors in different trajectory groups were also tracked to examine their sensitivity to sustained remission and relapse. We included 255 baseline-remitted depressed adolescents and a healthy control group (n=255) matched in age, sex, and race, sourced from the Adolescent Brain Cognitive Development Study. The linear mixed model was employed for the statistical analysis. The p factor not only effectively discriminated between remitted depressed adolescents and healthy controls but also robustly predicted the depression recurrence over a subsequent 2-year course. The specific internalizing factor could only differentiate remitted depressed adolescents from healthy controls. Additionally, a noteworthy longitudinal decline of the p factor in the sustained-remission group was observed. Psychopathology factors serve as the inherent and enduring measurement of long-term mental health aberrations. Longitudinal results indicate that the p factor is more sensitive to respond to sustained remission than the internalizing factor. The ability of the overall p factor to anticipate depression relapse, unlike the specific internalizing factor, suggests the clinical interventions should monitor and mitigate the coincident symptoms across all dimensions to preempt relapse of adolescent depression, rather than an exclusive focus on internalizing symptoms.

Real-world evidence study on the early use of cemiplimab in the UK: REACT-CEMI (Real World evidence of advanced CSCC treatment with cemiplimab).

Cemiplimab was licensed in the United Kingdom (UK) in 2019 for the treatment of patients with locally advanced and metastatic CSCC not suitable for curative surgery or radiotherapy (advanced CSCC [aCSCC]). No UK multi-center studies have investigated the real-world experience of cemiplimab post marketing authorization in aCSCC. This non-interventional retrospective study (10 UK centers) involved data collection from medical records of patients with aCSCC who initiated cemiplimab treatment between 2 July 2019 and 30 November 2020. The study period was a minimum of 12 and a maximum of 36 months post cemiplimab initiation. The primary objective was to describe the real-world clinical effectiveness of cemiplimab (primary outcome: overall response rate [ORR]). Of 105 patients, 70% (n=73/105) were male (median [range] age at index of 78.5 [55.4-93.2] years); most patients (63% [n=50/80]) had an Eastern Cooperative Oncology Group (ECOG) score of 1 and 62% (n=63/102) had metastatic disease. The ORR within 12 months was 42% (95% confidence interval [CI] 32%-51%) and the disease control rate was 62% (n=65/105). The median (95% CI) real-world progression-free survival and overall survival from index was 8.6 (6.0-18.7) and 21.0 (14.7-25.2) months, respectively. The median (range) number of cemiplimab infusions was 11.0 (1.0-44.0). Eighty-seven percent experienced no cemiplimab treatment interruptions; 13% (n=14/105) interrupted treatment due to immune-related adverse reactions (irARs) (47% [n=9/19] of treatment interruption events). Eighty-five percent (n=89/105) of patients had discontinued cemiplimab treatment by the end of the study; where reasons for discontinuation were recorded, 20% (n=17/87) discontinued due to the completion of their 2-year treatment course. Nineteen percent (n=20/105) of patients experienced irARs. Effectiveness and safety data in this study are broadly similar to previous real-world studies of cemiplimab and the EMPOWER-CSCC1 clinical trial; with our cohort representing a broader population (included immunocompromised and transplant patients). Results support the use of cemiplimab for the treatment of aCSCC in a real-world setting.