Optimizing the use of Ki-67 proliferative index as a prognostic biomarker in meningiomas using digital analysis.

OBJECTIVE: Ki-67 immunohistochemistry is widely used as a prognostic marker in meningiomas, but visual estimations tend to be imprecise. Whether the average Ki-67 over an entire slide, a particular block, or areas of high staining (hotspots) is prognostic for recurrence-free survival (RFS) and overall survival (OS) is unknown. This study aimed to generate evidence-based recommendations for the optimal use of Ki-67 immunohistochemistry in the workup of meningiomas. METHODS: All tissue blocks from a retrospective cohort of 221 patients with primary meningioma (141 WHO grade 1, 64 WHO grade 2, 16 WHO grade 3) were immunostained for Ki-67 and scanned using automated digital analysis software. QuPath was used to quantify the average Ki-67 proliferation index per slide as well as the Ki-67 hotspot in a 2.2-mm2 area within each slide. The best block was defined subjectively by a neuropathologist as the most representative tissue block from each case. The pathology report Ki-67 was determined by visual estimation. Age, sex, WHO grade, extent of resection, tumor location, and quantitative Ki-67 labeling were tested to determine risk factors for RFS and OS. RESULTS: Multivariable analyses demonstrated that WHO grade 2 (HR 2.42, p = 0.018), subtotal resection (HR 8.16, p < 0.0001), near-total resection (HR 2.24, p = 0.041), QuPath Ki-67 averaged across all blocks (HR per % increase = 1.72, p = 0.030), and pathology report Ki-67 (HR per % increase = 1.05, p = 0.0026) were associated with shorter RFS. The average Ki-67 in the best block, maximum across all slides, and maximum hotspot in the best block were not associated with RFS. Only male sex was independently associated with shorter OS (HR 8.52, p = 0.0003). The pathology report Ki-67 was, on average, 6.5 times higher than the QuPath average. CONCLUSIONS: These data on Ki-67 in meningiomas indicate the following: 1) visual estimation substantially overestimates Ki-67, 2) digital quantification of average Ki-67 across all tissue blocks provides more prognostic information than small hotspot regions or an entire single block, and 3) Ki-67 is not informative for OS. The results suggest that best practices for incorporating Ki-67 into meningioma prognostication include digital quantification of average Ki-67 over multiple blocks.

Feasibility of a contraceptive-specific electronic health record system to promote the adoption of pharmacist-prescribed contraceptive services in community pharmacies in the United States.

Objectives: Pharmacists in over half of the United States can prescribe contraceptives; however, low pharmacist adoption has impeded the full realization of potential public health benefits. Many barriers to adoption may be addressed by leveraging an electronic health records (EHR) system with clinical decision support tools and workflow automation. We conducted a feasibility study to determine if utilizing a contraceptive-specific EHR could improve potential barriers to the implementation of pharmacist-prescribed contraceptive services. Materials and Methods: 20 pharmacists each performed two standardized patient encounter simulations: one on the EHR and one on the current standard of care paper-based workflow. A crossover study design was utilized, with each pharmacist performing encounters on both standardized patients with the modality order randomized. Encounters were timed, contraceptive outputs were recorded, and the pharmacists completed externally validated workload and usability surveys after each encounter, and a Perception, Attitude, and Satisfaction survey created by the research team after the final encounter. Results: Pharmacists were more likely to identify contraceptive ineligibility using the EHR-based workflow compared to the paper workflow (P = .003). Contraceptive encounter time was not significantly different between the 2 modalities (P = .280). Pharmacists reported lower mental demand (P = .003) and greater perceived usefulness (P = .029) with the EHR-based workflow compared to the paper modality. Discussion and Conclusion: Pharmacist performance and acceptance of contraceptive services delivery were improved with the EHR workflow. Pharmacist-specific contraceptive EHR workflows show potential to improve pharmacist adoption and provision of appropriate contraceptive care.

Disaster healthcare disparities solutions: Part 1-Preparation.

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the first of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee workgroup conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product exploring disaster healthcare disparities seen in disaster. Many solutions for disaster healthcare disparities during preparation were found. Some of these solutions have been successfully implemented, while others are still theoretical. Solutions for disaster healthcare disparities seen in disaster preparation are achievable, but there is still much work to do. There are a variety of solutions that can be easily advocated for by disaster and nondisaster specialists, leading to better care for our patients.

Candida auris inpatient screening in collaboration with the public health department.

Candida auris is a multidrug-resistant fungal pathogen that is associated with nosocomial outbreaks in patients with extensive health care exposure and treatment outside the United States. The Ohio Department of Health recommends C auris screening in high-risk patients. However, this can be operationally difficult for many health care facilities. This report describes a C auris and carbapenem-resistant Enterobacterales inpatient screening program done in collaboration with state public health.

Disaster healthcare disparities solutions: Part 3-Recovery and mitigation.

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the third of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product. Many solutions for disaster healthcare disparities seen during recovery and mitigation were found. Some of these solutions have been successfully implemented and some remain theoretical. Solutions for disaster healthcare disparities seen during recovery and mitigation are achievable but there is still much work to do. Many of these solutions can be advocated for by nondisaster specialists.

Disaster healthcare disparities solutions: Part 2-Response.

The purpose of this study was to explore the potential solutions for disaster healthcare disparities. This paper is the second of a three-part series that was written by the Disaster Healthcare Disparities Workgroup of the American College of Emergency Physicians Disaster Preparedness and Response Committee. The committee conducted a literature review and chose articles most representative and demonstrative of solutions to disaster healthcare disparities found in a past workgroup product. Many solutions for disaster healthcare disparities during disaster response were found. Some of these solutions have been successfully implemented and some are hypothetical. Solutions for disaster healthcare disparities seen during response are achievable but there is still much work to do. A variety of the proposed solutions can be advocated for by nondisaster specialists leading to better care for all our patients.

Adaptations to sociality in the mimetic and auricular musculature of the African wild dog (Lycaon pictus).

The African wild dog (Lycaon pictus) is a highly social canid that engages in sophisticated, coordinated group hunting tactics to procure large game. It is one of the most effective hunters of the African savannah, due to its highly developed communication methods. It also has large, mobile ears which enhance its auditory capabilities while hunting and assist with thermoregulation. Recent research suggested that certain muscles of facial expression, particularly those involved with expressive eyebrow movement, evolved solely in domestic dogs (Canis familiaris) to facilitate communication with their human owners. However, it is unclear whether highly social wild canid species may also employ similar expressive eye communication. We performed detailed dissections of an adult male L. pictus to evaluate and describe its mimetic and auricular musculature. Overall, L. pictus has well-developed facial and ear muscles. Musculi levator anguli oculi medialis (LAOM) and retractor anguli oculi lateralis (RAOL), mimetic muscles of hypothesized importance in domestic dog-human non-verbal communication, are enlarged in L. pictus, comparable in size to those of domestic dogs, as is m. orbicularis oculi. This morphology suggests that ocular facial expressions contribute to within-pack communication in wild dogs and are not unique to domestic dogs. The auricular muscles of L. pictus are well-developed, supporting greater leverage and fine manipulation of its large, mobile ears. These muscular adaptations facilitate the highly social ecology of African wild dogs and challenge current interpretations about the unique nature of domestic dog facial expressions.

The development of an automated assessment system for resistance training movement.

Portable data collection devices and machine learning (ML) have been combined in autonomous movement analysis models for resistance training (RT) movements. However, input features for these models were mostly extracted empirically and subsequent models demonstrated limited interpretability and generalisability to real-world settings. This study aimed to investigate the utility of interpretable and generalisable modelling techniques and several data-driven feature extraction (FE) methods. This was achieved by developing machine learning movement analysis models for the barbell back squat and deadlift using markerless motion capture. 61 participants performed submaximal and maximal repetitions of both RT movements. Movement data was collected using two Azure Kinect cameras. Joint and segment kinematic variables were calculated from the collected depth imaging, and input features were extracted using traditional, manual FE methods and novel data-driven techniques. Classifiers were developed for several predefined technical deviations for both movements. Many of the addressed technical deviations could be classified with good levels of accuracy (≥70%) while the remainder were poor (55%-60%). Additionally, data-driven FE techniques were comparable to previous, traditional FE methods. Interpretable and generalisable modelling techniques can be utilised to good effect for certain classification tasks while data-driven FE techniques did not provide a consistent advantage over traditional FE methods.

Preliminary effects of a rural skin cancer prevention intervention for youths.

OBJECTIVES: To pilot and assess the feasibility, acceptability, and preliminary effects of the Rural Adult and Youth Sun (RAYS) protection program, a multilevel skin cancer preventive intervention for young children living in rural U.S. communities, delivered through community-organized team sports. METHOD: Three rural counties in Utah participated with two receiving the intervention and the third serving as a control. Youth sports leagues were recruited through recreation departments and the study took place from May through October 2021. Intervention leagues received sun protection supplies for players and coaches, educational materials for parents, and coaches were offered training on skin cancer and sun protection behaviors. RESULTS: The RAYS program is both feasible to deliver and acceptable to coaches, parents, and players. The intervention also demonstrates beneficial preliminary effects on components of observed child sun-protective behaviors, coach sun protection behaviors, knowledge of skin cancer prevention recommendations, and self-efficacy in skin cancer prevention. CONCLUSIONS: Multilevel interventions for skin cancer prevention among young children can be successfully delivered through community organizations and their settings. A priority moving forward is the identification of ways to optimize delivery of such programs to positively influence skin cancer preventive behaviors among children living in diverse rural areas. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Trazodone rescues dysregulated synaptic and mitochondrial nascent proteomes in prion neurodegeneration.

The unfolded protein response (UPR) is rapidly gaining momentum as a therapeutic target for protein misfolding neurodegenerative diseases, in which its overactivation results in sustained translational repression leading to synapse loss and neurodegeneration. In mouse models of these disorders, from Alzheimer's to prion disease, modulation of the pathway-including by the licensed drug, trazodone-restores global protein synthesis rates with profound neuroprotective effects. However, the precise nature of the translational impairment, in particular the specific proteins affected in disease, and their response to therapeutic UPR modulation are poorly understood. We used non-canonical amino acid tagging (NCAT) to measure de novo protein synthesis in the brains of prion-diseased mice with and without trazodone treatment, in both whole hippocampus and cell-specifically. During disease the predominant nascent proteome changes occur in synaptic, cytoskeletal and mitochondrial proteins in both hippocampal neurons and astrocytes. Remarkably, trazodone treatment for just 2 weeks largely restored the whole disease nascent proteome in the hippocampus to that of healthy, uninfected mice, predominantly with recovery of proteins involved in synaptic and mitochondrial function. In parallel, trazodone treatment restored the disease-associated decline in synapses and mitochondria and their function to wild-type levels. In conclusion, this study increases our understanding of how translational repression contributes to neurodegeneration through synaptic and mitochondrial toxicity via depletion of key proteins essential for their function. Further, it provides new insights into the neuroprotective mechanisms of trazodone through reversal of this toxicity, relevant for the treatment of neurodegenerative diseases via translational modulation.

Evaluation of a COVID-19 fundamental nursing care guideline versus usual care: The COVID-NURSE cluster randomized controlled trial.

AIM: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness. DESIGN: Parallel two-arm, cluster-level randomized controlled trial. METHODS: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses. RESULTS: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup. CONCLUSION: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required. IMPACT: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care. REPORTING METHOD: CONSORT and CONSERVE. PATIENT OR PUBLIC CONTRIBUTION: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings.

Heart failure management at home: a non-randomised prospective case-controlled trial (HeMan at Home).

BACKGROUND/OBJECTIVES: Heart failure (HF) is a growing clinical and economic burden for patients and health systems. The COVID-19 pandemic has led to avoidance and delay in care, resulting in increased morbidity and mortality among many patients with HF. The increasing burden of HF during the COVID-19 pandemic led us to evaluate the quality and safety of the Hospital at Home (HAH) for patients presenting to their community providers or emergency department (ED) with symptoms of acute on chronic HF (CHF) requiring admission. DESIGN/OUTCOMES: A non-randomised prospective case-controlled of patients enrolled in the HAH versus admission to the hospital (usual care, UC). Primary outcomes included length of stay (LOS), adverse events, discharge disposition and patient satisfaction. Secondary outcomes included 30-day readmission rates, 30-day ED usage and ED dwell time. RESULTS: Sixty patients met inclusion/exclusion criteria and were included in the study. Of the 60 patients, 40 were in the HAH and 20 were in the UC group. Primary outcomes demonstrated that HAH patients had slightly longer LOS (6.3 days vs 4.7 days); however, fewer adverse events (12.5% vs 35%) compared with the UC group. Those enrolled in the HAH programme were less likely to be discharged with postacute services (skilled nursing facility or home health). HAH was associated with increased patient satisfaction compared with Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) score in North Carolina. Secondary outcomes of 30-day readmission and ED usage were similar between HAH and UC. CONCLUSIONS: The HAH pilot programme was shown to be a safe and effective alternative to hospitalisation for the appropriately selected patient presenting with acute on CHF.

Androgen receptor inhibition suppresses anti-tumor neutrophil response against bone metastatic prostate cancer via regulation of TßRI expression.

Bone metastatic disease of prostate cancer (PCa) is incurable and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone neutrophils initially inhibit bone metastatic PCa growth yet metastatic PCa becomes resistant to neutrophil response. Further, neutrophils isolated from tumor-bone lost their ability to suppress tumor growth through unknown mechanisms. With this study, our goal was to define the impact of metastatic PCa on neutrophil function throughout tumor progression and to determine the potential of neutrophils as predictive biomarkers of metastatic disease. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identified that PCa progression dictates PMN cell surface markers and gene expression, but not cytotoxicity against PCa. Importantly, we also identified a novel phenomenon in which second generation androgen deprivation therapy (ADT) suppresses PMN cytotoxicity via increased transforming growth factor beta receptor I (TßRI). High dose testosterone and genetic or pharmacologic TßRI inhibition rescued androgen receptor-mediated neutrophil suppression and restored neutrophil anti-tumor immune response. These studies highlight the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa.

Understanding the Impacts of COVID Policy Changes on Access to Needed Supports for Families With Children Receiving Medicaid HCBS Waiver Services.

The COVID-19 pandemic necessitated rapid policy changes to address new demands on disability service systems. A statewide survey of families of people who received Medicaid funded home- and community-based (HCBS) long-term services and supports (LTSS) in one Midwestern state was conducted to understand (1) utilization of services allowed under the policy change, (2) family's experiences if their family member with a disability accessed the services, and (3) family's perspectives on the need for ongoing changes in the future. Overall, the results suggest that a subset of families took advantage of flexibilities introduced into service delivery models during the pandemic, and the changes-when accessed-addressed important needs that a large majority of families that accessed the services hoped would be sustained in the future.