Abstract: Background: The BCL-2 inhibitor venetoclax in combination with an anti-CD20 monoclonal antibody (rituximab or obinutuzumab) has demonstrated superior outcomes and manageable safety as compared to chemo-immunotherapy in phase III clinical trials for chronic lymphocytic leukemia (CLL). Moreover, venetoclax-based regimens induced high rates of undetectable minimal residual disease (uMRD). Prospective data on the effectiveness of venetoclax-based regimens specifically with regard to achieving uMRD in a real-world setting are still lacking. Here we report the first interim analysis for efficacy and safety of an ongoing nationwide real-world study of venetoclax based therapy for CLL/small lymphocytic lymphoma (SLL). Method: A prospective observational nationwide multicenter study. Treatment-naïve (TN) and relapsed/refractory (R/R) CLL/SLL patients were enrolled in 13 medical centers in Israel. The primary endpoint was clinical response, per physician assessment 12-months after the initiation of venetoclax treatment. Key secondary endpoints included progression free survival (PFS), overall survival (OS) and uMRD as assessed at a central laboratory by 8-color flow-cytometry. Results: Between February 10, 2019, and Jun 17, 2021 (data cut), 199 CLL/SLL patients were enrolled from 13 medical centers in Israel to receive venetoclax based therapy. The study included 83 TN and 116 R/R evaluable CLL/SLL patients with a median age of 69 years (range, 34-85) and 70.5 years (range, 25-91), respectively (Table 1). R/R patients had received a median of one prior therapy with a range up to 8, of these patients 60 (51.7%) were previously treated with a B-cell receptor inhibitor (BCRi) including ibrutinib in 52 (44.8%) and idelalisib in combination with rituximab in 6 (5.2%). TN patients had been treated with venetoclax in combination with obinutuzumab (92.8%) or rituximab (4.8%) and R/R patients received either venetoclax with rituximab (60.3%) or obinutuzumab (9.5%), venetoclax monotherapy (25.8%) or triple therapy with venetoclax, rituximab and ibrutinib in 5 (4.3%). Dose escalation of venetoclax to the recommended dose of 400 mg daily was achieved in 80.7% (n=67) of TN and 81% (n=94) of R/R patients. The median duration of ramp-up was 38 and 42 days in TN and R\R patients, respectively. Prior to therapy, tumor lysis syndrome (TLS) risk was considered high in 12% and 29.3% of TN and R/R patients, respectively (Table 1). Laboratory TLS occurred in one TN patient and 4 R/R patients, whereas 3 of the R/R patients experienced clinical TLS. Nineteen TN and 75 R/R patients had a follow-up of at least 12 months or discontinued study prematurely. The 12-month overall response rate (ORR) for TN and R/R patients was 89.5% [complete response (CR) 13 (68.4%), partial response (PR) 4 (21.1%)] and 73.3% [CR 37 (49.3%), PR 18 (24%)] , respectively. In the R/R cohort, the 12-month ORR among assessed patients was 67.6% (25/37) in BCRi-exposed versus 85.7% (30/35) in BCRi-naïve patients. At 12 months, peripheral blood uMRD ( & lt;0.01%) was achieved in 12 out of 14 (85.7%) TN and 26 out of 38 (68.4%) R/R evaluated patients. At a median follow-up of 5.1 months (range, 0.5-15.6) for TN and 10.1 months (range, 0-25.7) for R/R patients, the median PFS and OS, for both cohorts have not been reached. The estimated 12-month PFS was 90.9% for TN and 81.1% for R/R patients. For R/R patients with prior exposure to BCRi, the estimated 12-month PFS was 69.6% versus 94.8% in BCRi-naïve patients (figure 1). Grade ≥3 adverse events (AEs) were reported in 34.9% of TN patients and 43.9% R/R patients. The most frequent grade ≥3 AEs documented were neutropenia (TN: 19.2% and R/R 17.2%), infections (TN: 4.8% and R/R: 21.5%) and febrile neutropenia (TN: 2.4% and in R/R: 2.6%). COVID-19 occurred in 7 patients including one death. At the time of data cut, 10 deaths occurred, one TN and 9 R/R patients. Causes for death included infections (5 patients), disease progression (2 patients), acute myeloid leukemia/ myelodysplastic syndrome (2 patients) and a soft-tissue sarcoma (1 patient). Conclusions: This first interim analysis of our ongoing prospective real-world study of venetoclax-based treatment for TN and R/R CLL/SLL, demonstrates high efficacy together with a high proportion of undetectable MRD levels and a favorable toxicity profile. These efficacy results are comparable to those reported in previous Phase III clinical trials for CLL, with no new safety signals. Figure 1 Figure 1. Disclosures Herishanu: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; AstraZeneca: Honoraria. Goldschmidt: AbbVie: Consultancy, Research Funding. Itchaki: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Levi: AbbVie: Consultancy, Research Funding. Aviv: AbbVie: Honoraria, Research Funding. Fineman: AbbVie: Research Funding. Dally: AbbVie: Honoraria, Research Funding. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Abadi: AbbVie: Honoraria, Research Funding. Shvidel: AbbVie: Honoraria, Research Funding. Braester: AbbVie: Honoraria, Research Funding. Cohen: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Benjamini: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding.

Abstract: Heat stroke is a life-threatening condition affecting children worldwide. Rapid cooling remains the most important feature of emergency management. The accepted preferred method of evaporative cooling in the ED as listed by the reference text book endorsed by the Israeli Society of Pediatric Emergency Medicine (PEMI), is actively cooling the patient by spraying him with water and positioning fans to blow air across the body. Objective This study aimed to assess Israeli health care workers (HCWs) medical professionals’ knowledge and preparedness of treating heat stroke and recommend policy changes to ensure better treatment based on survey results. Design, settings and participants A cross-sectional survey of all HCWs working in an ED that accepts children was conducted. An online questionnaire was utilized to assess heat stroke management practices and available resources in all Israeli pediatric emergency departments (PEDs). Main results Data from 208 health care workers was analyzed. Only 30% of the participants reported ever treating a patient with exertional heat stroke. Two scenarios were presented to the participants: motor vehicle-related child hyperthermia (MVRCH) in an infant and an adolescent with exertional heat stroke. One hundred twenty-five (60%) and 83 (40%) participants, respectively, listed cool water with a fan as the primary mode of cooling, which is considered the appropriate preferred method of evaporative cooling in the PED. Certificated pediatric emergency medicine (PEM) physicians answered significantly more correctly regarding both scenarios’ management ( P   〈  0.001). Participants who were trained via simulation in the past, answered significantly more correctly regarding the exertional heat stroke scenario ( P   〈  0.01), however no difference was found regarding the MVRCH case. Conclusions: The present study exposes weaknesses in HCW knowledge, PED resources, and published PED policies for appropriate management of children following heat stroke. Our finding emphasizes the importance of both certificated PEM physicians attendance and simulation performance for implementing proper management of patients with heat stroke. A policy change should be performed among the Israeli PED community, with respect to establishing and implementing guidelines for treatment of exertional heat stroke. A future study, following an interventional simulation program is planned to be performed.

Abstract: Children who sustain major injuries are at risk of receiving insufficient pain relief and sedation, which can have physical and psychological repercussions. Heightened emotional distress can increase the likelihood of developing symptoms of post-traumatic stress. Providing sufficient analgesia and sedation for children with major trauma presents specific challenges, given the potential for drug-related adverse events, particularly in non-intubated patients. The current literature suggests that a relatively low percentage of pediatric patients receive adequate analgesia in pre-hospital and emergency department settings following major trauma. There are only sparse data on the safety of the provision of analgesia and sedation in children with major trauma in the pre-hospital and ED settings. The few studies that examined sedation protocols in this context highlight the importance of physician training and competency in managing pediatric airways. There is a pressing need for prospective studies that focus upon pediatric major trauma in the pre-hospital and emergency department setting to evaluate the benefits and risks of administering analgesia and sedation to these patients. The aim of this narrative review was to offer an updated overview of analgesia and sedation management in children with major trauma in pre-hospital and ED settings.

Abstract: Racial and ethnic minorities suffer significantly more than others in the wake of disasters. Despite the growing recognition of the importance of culturally competent health services, systematic cultural competence training in the medical education system is still scarce, especially in the field of emergency. The current study aimed to examine the effectiveness of an online culturally informed intervention for increasing cultural competence in emergencies among nursing students. Methods A randomized controlled trial was used to test the intervention effectiveness in increasing nursing students’ cultural competence in four domains: attitudes, knowledge, skills, and encounters. The study included 72 undergraduate nursing students recruited from two academic institutes. Participants were randomized (1:1 ratio) to an intervention ( n  = 34) and control group ( n  = 38). The study adheres to the Consolidated Standards of Reporting Trials (CONSORT). Data analysis was based on multivariate analysis of variance with repeated measures, followed by post hoc analyses with Bonferroni correction for multiple comparisons. Results Results showed that the intervention was effective in increasing the participants’ culturally competent knowledge. The effect of the intervention on the skills domain approached significance. No group differences were identified in the attitudes and the encounters domains. Conclusions An online culturally informed intervention, incorporated in the curriculum, was effective in enhancing the cognitive aspect of cultural competence (especially at the basic knowledge and understanding levels), but not other domains. Our results encourage the development of future intervention programs that are based on a deep understanding of local values, needs, and preferences.