Workplace Violence against Emergency Medical Services (EMS): a prospective 12-month cohort study evaluating prevalence and risk factors within a large, multistate EMS agency.

OBJECTIVES: To determine the prevalence and associated risk factors of workplace violence (WPV) experienced by emergency medical services (EMS) clinicians across a large, multistate ground/air EMS agency. METHODS: We used a prospective cohort study design from 12/1/2022-11/30/2023. A checkbox was added within the electronic medical record (EMR) asking staff to indicate whether WPV occurred. Patient characteristics, encounter (run), and crew factors were abstracted. Potential risk factors for WPV were assessed using logistic regression, with the occurrence of any form of violence as the primary outcome of interest. Models were both univariable, assessing each risk factor individually, and multivariable assessing all risk factors together to identify independent factors associated with higher risk of WPV. Multivariable model results were reported using odds ratios (aORs) and 95% confidence intervals. RESULTS: A total of 102,632 runs were included, 95.7% (n= 98,234) included checkbox documentation. There were 843 runs (0.86 per 100 runs, 95% CI 0.80-0.92) identified by EMS clinicians as WPV having occurred, including verbal abuse (n= 482), physical assault (n= 142), and both abuse and assault (n= 219). Risk factors for violence included male patient gender (aOR 1.45, 95% CI 1.24 - 1.70, p <0.001), Richmond Agitation-Sedation Scale (RASS) >1 (aOR 16.97, 95% CI 13.71 - 21.01, p < 0.001), and 9-1-1 runs to include emergent (P1; aOR 1.75, 95% CI: 1.17-2.63, p = 0.007) and urgent (P2; aOR 1.64, 95% CI 1.08-2.50, p = 0.021) priority, compared to P3/scheduled transfer or P4/trip requests. Factors associated with lower risk for violence included older patients (aOR per 10 years = 0.95, 95% CI 0.91 - 0.98, p = 0.007) and run time of day between 0601-1200 hours compared to 0000-0600 hours (aOR 0.67, 95% CI 0.51 - 0.88, p = 0.004). Only 2.7% of violent runs captured through the EMR were reported through official processes. CONCLUSIONS: Verbal and/or physical violence is recognized in nearly 1% of EMS runs. We recommend prioritizing WPV prevention and mitigation strategies around identified risk factors and simplifying the WPV reporting process in order to reduce staff administrative burden and encourage optimal capturing of violent events.

Analyzing the Impact of COVID-19 on the Well-Being of Pharmacists: A Narrative Review.

The COVID-19 pandemic impacted the mental, emotional, and physical health of healthcare professionals around the world. Despite research efforts to examine the experiences of physicians, nurses, and other professionals in healthcare, little has been shared about the experiences of pharmacists during the pandemic. A review of current evidence is needed to better understand the mental health experiences of pharmacists during the pandemic. This review aimed to understand the perceptions, experiences, and impacts on the mental, emotional, and psychological well-being of practicing pharmacists during the COVID-19 pandemic. A review of the literature was carried out by searching several electronic databases, which included Google Scholar, ScienceDirect, PubMed, DOAJ, JSTOR, PsycINFO, the ERIC Database (via EBSCOhost), and Academic Search Complete for studies published between 2020 and 2022. The search was conducted from September 10, 2022, to November 18, 2022, using Boolean operations and the following terms: Kansas, pharmacist, pharmacy, mental health, psychology, burnout, and well-being. Nine studies exploring the lived experiences of practicing pharmacists worldwide during the COVID-19 pandemic were included in this review. The literature surveyed includes three international studies, five national (USA) studies, one study from the Midwestern region of the USA, and one study from Kansas specifically. These studies revealed increased burnout prevalence, mental health distress, feelings of negativity related to the job, and an overall lack of wellness among pharmacists across the world during the pandemic. There is limited research on the perspectives and experiences of practicing pharmacists during the COVID-19 pandemic. Additional research is necessary to thoroughly understand pharmacists' experiences and how to further support their well-being.

Conference proceedings: Inaugural meeting of the consortium for autism, genetic neurodevelopmental disorders, and digestive diseases.

OBJECTIVES: Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), often experience a higher prevalence of gastrointestinal (GI) symptoms but have complex medical and behavioral comorbidities that make diagnosis and treatment difficult. A multi-stakeholder conference was convened to (a) determine patient and family experiences related to GI symptoms in NDDs, (b) review the clinicians' and researchers' perspectives, and (c) determine actionable steps for future research. METHODS: The Consortium for Autism, Neurodevelopmental Disorders and Digestive Diseases (CANDID; www.candidgi.com) virtually over 2 days in 2022 and consisted of four key activities: (1) an electronic family survey to assess underlying NDDs and GI symptoms, (2) a session focused on family perspectives, (3) review current clinical care and research, and (4) discussion to identify key next steps. Survey results were obtained electronically via the REDCap platform, and descriptive statistics were generated. The sessions were recorded, and themes were identified. RESULTS: The pre-conference survey ran for ~2 months and 739 families provided responses, with 634 completing all items. 83% had a child with an NDD under age 18, and most patients were White (85%) and non-Hispanic (87%). Constipation (80%), gastrointestinal reflux disease (51%), and bloating (49%) were the most frequently reported symptoms. Families gave unstructured feedback that the measures used in the surveys were often difficult to answer for patients with NDDs or who were nonspeaking. Family and clinical/scientific sessions identified several common themes, including (1) the need for less invasive diagnostic modalities, (2) the need to validate or adapt existing diagnostic measures (e.g., the Rome IV criteria) and outcome assessments, and (3) the need for enhanced attention to parent and caregiver input in treatment plans. CONCLUSIONS: Those providing care to children with NDDs, especially those with communication and cognitive challenges, should be aware of the differing needs in this community and consider family perspectives in managing, treating, and measuring GI issues. Future research should focus on adapting or creating diagnostic and research measures for those with NDDs, developing new diagnostic methods to account for diversity in neurodevelopment and communication, and improving methods for family and caregiver engagement in the care of GI disorders.

Visual assessments of 11C-Pittsburgh compound-B PET vs. 18F-flutemetamol PET across the age spectrum.

OBJECTIVE: Visual assessments of amyloid-ß PET, used for Alzheimer's disease (AD) diagnosis and treatment evaluation, require a careful approach when different PET ligands are utilized. Because the gray matter (GM) and white matter (WM) ligand bindings vary with age, the objective was to investigate the agreement between visual reads of 11C- and 18F-PET scans. METHODS: Cognitively unimpaired (CU) younger adults (N = 30; 39.5 ± 6.0 years), CU older adults (N = 30; 68.6 ± 5.9 years), and adults with AD (N = 22; 67.0 ± 8.5 years) underwent brain MRI, 11C-Pittsburgh compound-B (PiB)-PET, and 18F-flutemetamol-PET. Amyloid-ß deposition was assessed visually by two nuclear medicine specialists on 11C-PiB-PET and 18F-flutemetamol-PET, and quantitatively by PET centiloids. RESULTS: Seventy-two 11C-PiB-PET and 18F-flutemetamol-PET visual reads were concordant. However, 1 18F-flutemetamol-PET and 9 11C-PiB-PET were discordant with quantitative values. In four additional cases, while 11C-PiB-PET and 18F-flutemetamol-PET visual reads were concordant, both were discordant with quantitative values. Disagreements in CU younger adults were only with 11C-PiB-PET visual reads. The remaining disagreements were with CU older adults. CONCLUSION: Age, GM/WM binding, amyloid-ß load, and disease severity may affect visual assessments of PET ligands. Increase in WM binding with age causes a loss of contrast between GM and WM on 11C-PiB-PET, particularly in CU younger adults, leading to false positivity. In CU older adults, increased WM signal may bleed more into cortical regions, hiding subtle cortical uptake, especially with 18F-flutemetamol, whereas 11C-PiB can detect true regional positivity. Understanding these differences will improve patient care and treatment evaluation in clinic and clinical trials.

A modular system for programming multistep activation of endogenous genes in stem cells.

Although genomes encode instructions for mammalian cell differentiation with rich syntactic relationships, existing methods for genetically programming cells have modest capabilities for stepwise regulation of genes. Here, we developed a sequential genetic system that enables transcriptional activation of endogenous genes in a preprogrammed, stepwise manner. The system relies on the removal of an RNA polymerase III termination signal to induce both the transcriptional activation and the DNA endonuclease activities of a Cas9-VPR protein to effect stepwise progression through cascades of gene activation events. The efficiency of the cascading system enables a new dimension for cellular programming by allowing the manipulation of the sequential order of gene activation for directing the differentiation of human stem cells. One-Sentence Summary: Development of a synthetic biology system for preprogrammed, stepwise activation of endogenous genes.

Patient-derived organoid model of olfactory ensheathing cell tumor.

KEY POINTS: We developed a culture model of a human olfactory ensheathing cell tumor. Cultured organoids resemble normal ensheathing cells. Assays suggest that this model provides a tool for studying the roles of these glial cells in the maintenance of the peripheral olfactory system.

Patient-reported outcomes in the subpopulation of patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy compared with chemotherapy alone in the ENGOT-EN6-NSGO/GOG3031/RUBY trial.

OBJECTIVE: In the ENGOT-EN6-NSGO/GOG3031/RUBY trial, dostarlimab+carboplatin-paclitaxel demonstrated significant improvement in progression free survival and a positive trend in overall survival compared with placebo+carboplatin-paclitaxel, with manageable toxicity, in patients with primary advanced or recurrent endometrial cancer. Here we report on patient-reported outcomes in the mismatch repair-deficient/microsatellite instability-high population, a secondary endpoint in the trial. METHODS: Patients were randomized 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo monotherapy every 6 weeks for ≤3 years or until disease progression. Patient-reported outcomes, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Endometrial Cancer Module, were prespecified secondary endpoints. A mixed model for repeated measures analysis, a prespecified exploratory analysis, was conducted to generate least-squares means to compare between-treatment differences while adjusting for correlations across multiple time points within a patient and controlling for the baseline value. Results are provided with 2-sided, nominal p values. RESULTS: Of 494 patients enrolled, 118 were mismatch repair-deficient/microsatellite instability-high. In this population, mean change from baseline to end of treatment showed visual improvements in global quality of life (QoL), emotional and social function, pain, and back/pelvis pain for dostarlimab+carboplatin-paclitaxel. Meaningful differences (least-squares mean [standard error]) favoring the dostarlimab arm were reported for change from baseline to end of treatment for QoL (14.7 [5.45]; p=0.01), role function (12.7 [5.92]); p=0.03), emotional function (14.3 [4.92]; p<0.01), social function (13.5 [5.43]; p=0.01), and fatigue (-13.3 [5.84]; p=0.03). CONCLUSIONS: Patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer receiving dostarlimab+carboplatin-paclitaxel demonstrated improvements in several QoL domains over patients receiving placebo+carboplatin-paclitaxel. The observed improvements in progression free survival and overall survival while improving or maintaining QoL further supports dostarlimab+carboplatin-paclitaxel as a standard of care in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT03981796.

Regulation of Kv1.2 redox-sensitive gating by the transmembrane lectin LMAN2.

Kv1.2 potassium channels influence excitability and action potential propagation in the nervous system. Unlike closely-related Kv1 channels, Kv1.2 exhibits highly variable voltage-dependence of gating, attributed to regulation by unidentified extrinsic factors. Variability of Kv1.2 gating is strongly influenced by the extracellular redox potential, and we demonstrate that Kv1.2 currents in dorsal root ganglion sensory neurons exhibit similar variability and redox sensitivity as observed when the channel is heterologously expressed in cell lines. We used a functional screening approach to test the effects of candidate regulatory proteins on Kv1.2 gating, using patch clamp electrophysiology. Among 52 candidate genes tested, we observed that co-expression with the transmembrane lectin LMAN2 led to a pronounced gating shift of Kv1.2 activation to depolarized voltages in CHO and L(tk-) cell lines, accompanied by deceleration of activation kinetics. Overexpression of LMAN2 promoted a slow gating mode of Kv1.2 that mimics the functional outcomes of extracellular reducing conditions, and enhanced sensitivity to extracellular reducing agents. In contrast, shRNA-mediated knockdown of endogenous LMAN2 in cell lines reduced Kv1.2 redox sensitivity and gating variability. Kv1.2 sensitivity to LMAN2 is abolished by mutation of neighboring residues F251 and T252 in the intracellular S2-S3 linker, and these also abolish redox-dependent gating changes, suggesting that LMAN2 influences the same pathway as redox for Kv1.2 modulation. In conclusion, we identified LMAN2 as a candidate regulatory protein that influences redox-dependent modulation of Kv1.2, and clarified the structural elements of the channel that are required for sensitivity.

Diagnostic dilemma: Leber's hereditary optic neuropathy in a 70-year-Old woman.

Purpose: Reports of atypical cases have increased awareness that Leber's hereditary optic neuropathy (LHON) is not solely a disease of young men. Here, we present a case of a 70-year-old woman who presented with bilateral sequential loss of vision, and, after several diagnostic dilemmas, was ultimately found to have LHON. Observations: Our patient presented with a one-month history of progressive central vision loss in the right eye. Her visual acuities were 20/200-1 and 20/25-2. She had no afferent pupillary defect and intraocular pressures were normal. Fundus examination revealed cup-to-disc ratios of 0.9 and 0.7 with an inferior notch on the right. Visual fields showed superior arcuate and cecocentral depressions on the right and an inferior nasal step on the left. Ocular coherence tomography showed bilateral, superior and inferior retinal nerve fiber layer thinning. She was diagnosed with normal-tension glaucoma. Laboratory studies and neuroimaging were unremarkable. One month later, she presented with new central vision loss in the left eye. Ocular coherence tomography revealed new, mild optic nerve swelling in the left eye. Due to concern for an acute-on-chronic process, she was hospitalized and treated with intravenous steroids and later plasmapheresis with modest improvement. An extensive laboratory evaluation, lumbar puncture, temporal artery biopsy, and PET CT were normal. Mitochondrial genetic testing was ordered. After a six-week delay, the results revealed a pathogenic variant at mitochondrial position 11778, consistent with a diagnosis of LHON. She began treatment with idebenone. At the most recent visit, her vision had improved to 20/40 and 20/30. Conclusions and importance: LHON is typically not part of the initial differential diagnosis of an optic neuropathy in patients outside the typical demographic. As genetic testing has become more widely available, clinicians should consider including LHON in their differential diagnosis of any optic neuropathy, especially if other, more common causes have been ruled out.

Dose de-intensified 3-day photon, proton, or brachytherapy: a nonrandomized controlled partial breast irradiation trial.

BACKGROUND: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. METHODS: A multicenter nonrandomized controlled trial with primary outcome of adverse cosmesis at 3 years versus pre-PBI. Eligibility criteria were ≥ age 50 years treated with breast-conserving surgery for node-negative estrogen receptor positive (ER+) invasive breast cancer or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (RBE) and brachytherapy 21 Gy in 3 fractions. Radiotherapy technique and use of adjuvant endocrine therapy was selected at physician and patient discretion. RESULTS: Between June 17, 2015 and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. 126 (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). 54.0% of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline, 2.3% at 3 years (difference -12.2%, 95% CI (-100%, -6.4%)). Adverse cosmesis at last-follow-up, with median follow-up 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient reported outcomes, and just two grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. 5-year local recurrence-free and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences amongst 60 patients with invasive breast cancer and Ki67 ≤ 13.25%. CONCLUSIONS: De-intensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the pre-specified criteria for acceptability. This approach is an attractive option for small node-negative ER+ BC and DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02453737.

Evaluation of Mental Health and Well-Being Among Kansas Pharmacists Post-COVID-19 Pandemic.

Background COVID-19 has profoundly affected pharmacists, causing burnout from heavier workloads, personal stressors, and disrupted healthcare delivery. Research on pharmacists' mental health during the pandemic, especially in rural areas like Kansas, remains limited. Objectives This study aimed to understand perceptions, experiences, and impacts on the mental, emotional, and psychological well-being of active Kansas pharmacists during the COVID-19 pandemic, including evaluating workplace modifications on mental health. Methods Kansas licensed pharmacists were recruited via email distributions through five Kansas pharmacy organizations and informal referrals among colleagues. After consenting, respondents completed a 15-minute, 28-question survey via Qualtrics. The survey included 11 questions concerning demographics and employment characteristics, along with 17 questions designed to assess the impact of COVID-19 on mental health, structured according to existing literature. Participation was uncompensated, and incomplete surveys were omitted from the analysis. Results One hundred and seven respondents (83.59% completion) represented 3.25% of Kansas's 3,290 pharmacists. They were aged 26-66 (M=38.7), the majority female (72.57%) and white (84.84%), with 14.24 years average practice duration (SD=10.94). Data covered 12 rural and 11 urban counties, with 50.91% staff pharmacists and 22.73% pharmacy managers. Many worked over 40 hours weekly in 13 settings. Findings showed increased workload (24.68%), medication shortages (24.03%), and burnout (24.32%) affecting job considerations. Workplace changes impacted personal mental health, with the main stressors being work-related factors (19.21%), social distancing (18.95%), and health concerns (12.63%). Conclusion This study underscores the pandemic's profound toll on Kansas pharmacists' mental, emotional, and physical health, leading to burnout, job dissatisfaction, and decreased effectiveness. It emphasizes the urgency of organizational interventions.

Generative AI in oncological imaging: Revolutionizing cancer detection and diagnosis.

Generative AI is revolutionizing oncological imaging, enhancing cancer detection and diagnosis. This editorial explores its impact on expanding datasets, improving image quality, and enabling predictive oncology. We discuss ethical considerations and introduce a unique perspective on personalized cancer screening using AI-generated digital twins. This approach could optimize screening protocols, improve early detection, and tailor treatment plans. While challenges remain, generative AI in oncological imaging offers unprecedented opportunities to advance cancer care and improve patient outcomes.

Hyaluronic acid and urology: a systematic review and meta-analysis.

INTRODUCTION: The use of hyaluronic acid as a nonsurgical treatment for various conditions within urology has been of great interest in recent literature. OBJECTIVES: In this study, we aimed to provide an updated review and analysis of the current state of hyaluronic acid use in urology, characterize its adverse effects, and briefly discuss future directions of research for hyaluronic acid in urology. METHODS: PubMed searches were run utilizing multiple terms, including "hyaluronic acid," "penile," "augmentation," "Peyronie disease," "premature ejaculation," and "cosmetic urology," among other related iterations. Relevant data extracted included International Index of Erectile Function score, intravaginal ejaculatory latency, glans circumference, penile girth, and plaque size. We also included studies which reported on complications of hyaluronic acid injections. Aggregated analysis was performed on studies with complete pre and post injection data at time closest to 6 months postinjection. RESULTS: A total of 33 studies met our inclusion criteria. Studies had marked heterogeneity in design, but most reported positive results. A total of 16 studies were included in our analysis. Intravaginal ejaculatory latency, penile girth, glans circumference, and International Index of Erectile Function were all increased on a fixed-effects model. Reduction in plaque size was not significant (P = .069). Complications were rare. CONCLUSION: Literature on hyaluronic acid for urologic issues demonstrates promising results; however, the quality of studies was variable. Our analysis of these studies largely corroborates these findings; however, the results are limited by the data available. Hyaluronic acid may be promising, but we highly implore standardization of study regimens in randomized controlled trials.

Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer.

BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

The autophagy proteome in the brain.

As one of the most important cellular housekeepers, autophagy directly affects cellular health, homeostasis, and function. Even though the mechanisms behind autophagy are well described, how molecular alterations and dysfunctions can lead to pathology in disease contexts still demands deeper investigation. Proteomics is a widely employed tool used to investigate molecular alterations associated with pathological states and has proven useful in identifying alterations in protein expression levels and post-translational modifications in autophagy. In this narrative review, we expand on the molecular mechanisms behind autophagy and its regulation, and further compile recent literature associating autophagy disturbances in context of brain disorders, utilizing discoveries from varying models and species from rodents and cellular models to human post-mortem brain samples. To outline, the canonical pathways of autophagy, the effects of post-translational modifications on regulating each step of autophagy, and the future directions of proteomics in autophagy will be discussed. We further aim to suggest how advancing proteomics can help further unveil molecular mechanisms with regard to neurological disorders.