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It is important to limit dwelling infiltration to reduce energy demand and help meet national climate change commitments while concurrently providing sufficient ventilation to deliver adequate indoor air quality. DOMVENT3D is a model of infiltration and exfiltration that assumes a linear pressure distribution over any number of uniformly porous facades and integrates the airflow rate in the vertical plane to predict the theoretically correct airflow rate through them. DOMVENT3D is a new development of an existing two-dimensional model of infiltration that provides more opportunities for investigating a greater number of dwellings than was previously possible. Initial testing suggests that DOMVENT3D is mathematically robust and is suitable for modelling a wide variety of dwelling types and geometries to assist engineers and policy makers.Practical application: The modern building services engineer may be required to model airflow networks in a building to balance the conflicting needs of energy consumption reduction and occupant health. Limiting exfiltration is one method of reducing heat losses from a building and so there is a need to model it accurately. This article presents a new model of infiltration and exfiltration through a uniformly porous facade that can be incorporated within advanced complex airflow network tools or applied using a simple spreadsheet. [ABSTRACT FROM AUTHOR]

Arctic shorelines are vulnerable to climate change impacts as sea level rises, permafrost thaws, storms intensify, and sea ice thins. Seventy-five years of aerial and satellite observations have established coastal erosion as an increasing Arctic hazard. However, other hazards at play-for instance, the cumulative impact that sea-level rise and permafrost thaw subsidence will have on permafrost shorelines-have received less attention, preventing assessments of these processes' impacts compared to and combined with coastal erosion. Alaska's Arctic Coastal Plain (ACP) is ideal for such assessments because of the high-density observations of topography, coastal retreat rates, and permafrost characteristics, and importance to Indigenous communities and oilfield infrastructure. Here, we produce 21st-century projections of Arctic shoreline position that include erosion, permafrost subsidence, and sea-level rise. Focusing on the ACP, we merge 5 m topography, satellite-derived coastal lake depth estimates, and empirical assessments of land subsidence due to permafrost thaw with projections of coastal erosion and sea-level rise for medium and high emissions scenarios from the Intergovernmental Panel on Climate Change's AR6 Report. We find that by 2100, erosion and inundation will together transform the ACP, leading to 6-8x more land loss than coastal erosion alone and disturbing 8-11x more organic carbon. Without mitigating measures, by 2100, coastal change could damage 40 to 65% of infrastructure in present-day ACP coastal villages and 10 to 20% of oilfield infrastructure. Our findings highlight the risks that compounding climate hazards pose to coastal communities and underscore the need for adaptive planning for Arctic coastlines in the 21st century., Competing Interests: Competing interests statement:The authors declare no competing interest.

Comparative genomic studies of social insects suggest that changes in gene regulation are associated with evolutionary transitions in social behavior, but the activity of predicted regulatory regions has not been tested empirically. We used self-transcribing active regulatory region sequencing, a high-throughput enhancer discovery tool, to identify and measure the activity of enhancers in the socially variable sweat bee, Lasioglossum albipes. We identified over 36,000 enhancers in the L. albipes genome from 3 social and 3 solitary populations. Many enhancers were identified in only a subset of L. albipes populations, revealing rapid divergence in regulatory regions within this species. Population-specific enhancers were often proximal to the same genes across populations, suggesting compensatory gains and losses of regulatory regions may preserve gene activity. We also identified 1,182 enhancers with significant differences in activity between social and solitary populations, some of which are conserved regulatory regions across species of bees. These results indicate that social trait variation in L. albipes is associated with the fine-tuning of ancient enhancers as well as lineage-specific regulatory changes. Combining enhancer activity with population genetic data revealed variants associated with differences in enhancer activity and identified a subset of differential enhancers with signatures of selection associated with social behavior. Together, these results provide the first empirical map of enhancers in a socially flexible bee and highlight links between cis-regulatory variation and the evolution of social behavior., Competing Interests: Conflict of Interest The authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Objective: To develop machine learning models using patient and migraine features that can predict treatment responses to commonly used migraine preventive medications., Background: Currently, there is no accurate way to predict response to migraine preventive medications, and the standard trial-and-error approach is inefficient., Methods: In this cohort study, we analyzed data from the Mayo Clinic Headache database prospectively collected from 2001 to December 2023. Adult patients with migraine completed questionnaires during their initial headache consultation to record detailed clinical features and then at each follow-up to track preventive medication changes and monthly headache days. We included patients treated with at least one of the following migraine preventive medications: topiramate, beta-blockers (propranolol, metoprolol, atenolol, nadolol, timolol), tricyclic antidepressants (amitriptyline, nortriptyline), verapamil, gabapentin, onabotulinumtoxinA, and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) (erenumab, fremanezumab, galcanezumab, eptinezumab). We pre-trained a deep neural network, "TabNet," using 145 variables, then employed TabNet-embedded data to construct prediction models for each medication to predict binary outcomes (responder vs. non-responder). A treatment responder was defined as having at least a 30% reduction in monthly headache days from baseline. All model performances were evaluated, and metrics were reported in the held-out test set (train 85%, test 15%). SHapley Additive exPlanations (SHAP) were conducted to determine variable importance., Results: Our final analysis included 4260 patients. The responder rate for each medication ranged from 28.7% to 34.9%, and the mean time to treatment outcome for each medication ranged from 151.3 to 209.5 days. The CGRP mAb prediction model achieved a high area under the receiver operating characteristics curve (AUC) of 0.825 (95% confidence interval [CI] 0.726, 0.920) and an accuracy of 0.80 (95% CI 0.70, 0.88). The AUCs of prediction models for beta-blockers, tricyclic antidepressants, topiramate, verapamil, gabapentin, and onabotulinumtoxinA were: 0.664 (95% CI 0.579, 0.745), 0.611 (95% CI 0.562, 0.682), 0.605 (95% CI 0.520, 0.688), 0.673 (95% CI 0.569, 0.724), 0.628 (0.533, 0.661), and 0.581 (95% CI 0.550, 0.632), respectively. Baseline monthly headache days, age, body mass index (BMI), duration of migraine attacks, responses to previous medication trials, cranial autonomic symptoms, family history of headache, and migraine attack triggers were among the most important variables across all models. A variable could have different contributions; for example, lower BMI predicts responsiveness to CGRP mAbs and beta-blockers, while higher BMI predicts responsiveness to onabotulinumtoxinA, topiramate, and gabapentin., Conclusion: We developed an accurate prediction model for CGRP mAbs treatment response, leveraging detailed migraine features gathered from a headache questionnaire before starting treatment. Employing the same methods, the model performances for other medications were less impressive, though similar to the machine learning models reported in the literature for other diseases. This may be due to CGRP mAbs being migraine-specific. Incorporating medical comorbidities, genomic, and imaging factors might enhance the model performance. We demonstrated that migraine characteristics are important in predicting treatment responses and identified the most crucial predictors for each of the seven types of preventive medications. Our results suggest that precision migraine treatment is feasible., (© 2024 American Headache Society.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice., Summary: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies., Conclusion: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Vancomycin is recommended as first-line treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, dosed by area-under-the-curve (AUC) with an assumed minimum inhibitory concentration (MIC) of 1 mcg/mL via broth microdilution. The purpose of this study was to compare effectiveness of AUC-based and trough-based dosing in MRSA bacteremia with an MIC > 1 mcg/mL via Etest. Methods: This was a retrospective, observational cohort that compared vancomycin dosed by AUC or trough between January 1, 2017 and September 1, 2022. The primary outcome was a composite of treatment failure defined as peristent bacteremia ≥ 7 days, inpatient mortality within 90 days, or microbiologic relapse or readmission within 30 days. Secondary outcomes compared nephrotoxicity, hospital and ICU length of stay, MIC differences, and difference in exposure measured by AUC. Results: Twenty-four patients in each group met inclusion criteria. For the primary outcome, there was no statistical difference in treatment failure between trough and AUC groups, respectively [10 (41.7%) vs 10 (41.7%), P  = 1.000]. There was no statistical difference in secondary outcomes, with incidence of nephrotoxicity [3 (12.5%) trough vs 2 (8.33%) AUC, P  = 1.000] and median AUC exposure over treatment course [502.9 mcg.h/mL (454.1-599.9) vs 474 mcg.h/mL (435.3-533), P  = .312] similar between groups. Conclusion: There was no statistically significant difference in treatment failure for vancomycin by AUC or trough with an Etest MIC > 1 mcg/mL. Overall exposure to vancomycin and incidence of nephrotoxicty were numerically higher in the trough group, suggesting that dosing by AUC may limit exposure without impact on treatment failure., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Daptomycin use for gram-positive infections has increased. This cost minimization analysis aimed to determine cost and/or time savings of daptomycin over vancomycin. The estimated hospital cost savings was US$166.41 per patient, and pharmacist time saved of almost 20 minutes per patient. Daptomycin has the potential to save both time and money., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In 2007, the Anaktuvuk River fire burned more than 1000 km 2 of arctic tundra in northern Alaska, ~ 50% of which occurred in an area with ice-rich syngenetic permafrost (Yedoma). By 2014, widespread degradation of ice wedges was apparent in the Yedoma region. In a 50 km 2 area, thaw subsidence was detected across 15% of the land area in repeat airborne LiDAR data acquired in 2009 and 2014. Updating observations with a 2021 airborne LiDAR dataset show that additional thaw subsidence was detected in < 1% of the study area, indicating stabilization of the thaw-affected permafrost terrain. Ground temperature measurements between 2010 and 2015 indicated that the number of near-surface soil thawing-degree-days at the burn site were 3 × greater than at an unburned control site, but by 2022 the number was reduced to 1.3 × greater. Mean annual ground temperature of the near-surface permafrost increased by 0.33 °C/yr in the burn site up to 7-years post-fire, but then cooled by 0.15 °C/yr in the subsequent eight years, while temperatures at the control site remained relatively stable. Permafrost cores collected from ice-wedge troughs (n = 41) and polygon centers (n = 8) revealed the presence of a thaw unconformity, that in most cases was overlain by a recovered permafrost layer that averaged 14.2 cm and 18.3 cm, respectively. Taken together, our observations highlight that the initial degradation of ice-rich permafrost following the Anaktuvuk River tundra fire has been followed by a period of thaw cessation, permafrost aggradation, and terrain stabilization., (© 2024. The Author(s).)

Globally, coastal communities experience flood hazards that are projected to worsen from climate change and sea level rise. The 100-year floodplain or record flood are commonly used to identify risk areas for planning purposes. Remote communities often lack measured flood elevations and require innovative approaches to estimate flood elevations. This study employs observation-based methods to estimate the record flood elevation in Alaska communities and compares results to elevation models, infrastructure locations, and sea level rise projections. In 46 analyzed communities, 22% of structures are located within the record floodplain. With sea level rise projections, this estimate increases to 30-37% of structures by 2100 if structures remain in the same location. Flood exposure is highest in western Alaska. Sea level rise projections suggest northern Alaska will see similar flood exposure levels by 2100 as currently experienced in western Alaska. This evaluation of record flood height, category, and history can be incorporated into hazard planning documents, providing more context for coastal flood exposure than previously existed for Alaska. This basic flood exposure method is transferable to other areas with similar mapping challenges. Identifying current and projected hazardous zones is essential to avoid unintentional development in floodplains and improve long-term safety., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: To evaluate temporal trends in the prevalence of gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) in the southeastern United States. Secondary objective was to examine the use of novel β-lactams for GNB with DTR by both antimicrobial use (AU) and a novel metric of adjusted AU by microbiological burden (am-AU)., Design: Retrospective, multicenter, cohort., Setting: Ten hospitals in the southeastern United States., Methods: GNB with DTR including Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter spp. from 2015 to 2020 were tracked at each institution. Cumulative AU of novel β-lactams including ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, and cefiderocol in days of therapy (DOT) per 1,000 patient-days was calculated. Linear regression was utilized to examine temporal trends in the prevalence of GNB with DTR and cumulative AU of novel β-lactams., Results: The overall prevalence of GNB with DTR was 0.85% (1,223/143,638) with numerical increase from 0.77% to 1.00% between 2015 and 2020 ( P = .06). There was a statistically significant increase in DTR Enterobacterales (0.11% to 0.28%, P = .023) and DTR Acinetobacter spp. (4.2% to 18.8%, P = .002). Cumulative AU of novel β-lactams was 1.91 ± 1.95 DOT per 1,000 patient-days. When comparing cumulative mean AU and am-AU, there was an increase from 1.91 to 2.36 DOT/1,000 patient-days, with more than half of the hospitals shifting in ranking after adjustment for microbiological burden., Conclusions: The overall prevalence of GNB with DTR and the use of novel β-lactams remain low. However, the uptrend in the use of novel β-lactams after adjusting for microbiological burden suggests a higher utilization relative to the prevalence of GNB with DTR., Competing Interests: Potential conflicts of interest. D.C. reports that he is pending a patent with Genus, group, species, and/or strain-specific 16s rdna sequences. B.J. reports that he is the member of the speaker’s bureau for Abbie, Paratek, Innoviva, and Ferring. M.A. reports that he serves on IDSA Antimicrobial Resistance Committee, International Working Group for Diabetic Foot Infection Guideline Panel, and WHO Antimicrobial Resistance Expert Group on Human Health Research. P.B. reports that she has two ongoing grants (CDC-RFA-CK22-2203 and University of South Carolina Center for Rural and Primary Healthcare). J.A.J. reports that she is on the advisory board for Entasis Therapeutics and Shionogi. Potential conflicts of interest. All other authors report no conflicts of interest relevant to this article., (© The Author(s) 2024.)

Rapid eye movement (REM) sleep behavior disorder (RBD) classically presents with repetitive complex motor behavior during sleep with associated dream mentation. The diagnosis requires a history of repetitive complex motor behaviors and polysomnographic demonstration of REM sleep without atonia (RSWA) or capturing dream enactment behaviors. RSWA is best evaluated in the chin or flexor digitorum superficialis muscles. The anterior tibialis muscle is insufficiently accurate to be relied upon solely for RBD diagnosis. RBD may present with parkinsonism or cognitive impairment or may present in isolation. Patients should be monitored for parkinsonism, autonomic failure, or cognitive impairment., Competing Interests: Disclosure Dr Jones and Dr McCarter report no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI., Methods: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021., Results: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q 1 -Q 3 ) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%., Conclusions: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards., (© 2024. The Author(s).)

Background: Job-exposure matrices (JEMs) are often used for exposure assessment in occupational exposure and epidemiology studies. However, general population JEMs are difficult to find and access for workers in the United States of America., Objective: We aimed to use publicly available information to develop a JEM-like exposure assessment method to determine exposure to a wide range of occupational agents in a wide range of occupations for US general population studies., Methods: We used information from the US Department of Labor's Occupational Information Network database (O*NET) for 19,636 job tasks and 974 civilian occupations. We used automated keyword searches to identify 1,804 job tasks that involved exposure to 50 occupational agents. We had 2 reviewers determine whether each identified job task actually involved exposure to the 50 occupational agents. We had a third reviewer, a certified industrial hygienist, assess any job task and exposure for which the first 2 reviewers disagreed. For each U.S. Census 2010 occupation code, we used this information to derive 3 exposure variables for each occupational agent: ever exposure, number of job tasks of exposure, and frequency of exposure., Results: Our keyword searches identified a median of 10 (interquartile range [IQR]: 43.75) job tasks for each occupational agent, and the maximum was 308. We determined job tasks actually involved exposure to 45 occupational agents, including solvents, air pollution, pesticides, radiation, metals, etc. We derived the 3 exposure variables for these 45 occupational agents for 516 U.S. Census 2010 occupation codes. The median percentage for ever exposure to individual occupational agents was 1.16% (IQR: 1.74%), and the maximum was 11.43%., Conclusions: Our JEM-like exposure assessment method based on O*NET information can be used to determine exposure to a wide range of occupational agents in a wide range of occupations for the US general population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Purpose: Women are underrepresented in academic radiation oncology (RO), particularly in leadership positions. In this study, we sought to better understand the characteristics of individuals who currently serve as academic RO chairpersons at institutions with an associated Accreditation Council for Graduate Medical Education-accredited RO residency training program., Methods and Materials: We created a database of academic RO chairpersons in the United States by using publicly available sources, including residency training program websites, hospital/institutional websites, Doximity, LinkedIn, the American Society for Radiation Oncology (ASTRO) website, the American College of Radiation Oncology website, and the National Plan and Provider Enumeration System National Provider Identifier Registry. We used the χ 2 Goodness of Fit test, Mann-Whitney U test, and Fisher exact test via R version 4.1.1 to evaluate for statistical significance among categorical variables, medians, and proportions, respectively., Results: We identified 85 of the 90 chairpersons (94.4%) currently serving at institutions with an Accreditation Council for Graduate Medical Education-accredited RO residency training program, 5 of whom hold interim positions and were thus excluded from further analyses. Of the remaining 80 chairpersons, 9 (11.3%) are women, and 71 (88.8%) are men ( P < .01). Seventy-six chairpersons (95.0%) are full professors, and 19 (23.8%) hold dual MD PhD degrees. Thirty-two chairpersons (40.0%) hold an official leadership role in a cancer center affiliated with their current institution (43.7% of men vs 11.1% of women; P = .08). Seventy-three chairpersons (91.3%) secured their current positions a median of 16 years (range, 6-33 years) after completing RO residency. Thirty-five chairpersons (43.8%) were promoted to chair from positions within their current institutions (40.8% of men vs 66.7% of women; P = .17). The majority of chairpersons are ASTRO Fellows (62.5%); notably fewer are ASTRO (5.0%) or American College of Radiation Oncology (2.5%) Gold Medalists. Eight RO residency programs trained more than half of current chairpersons., Conclusion: Significantly more men than women currently serve as RO chairpersons. Future interventions that promote the recruitment, retention, and promotion of talented women in academic RO should be considered., Competing Interests: Kristin Hsieh is the 2023 American Society for Radiation Oncology AstraZeneca Radiation Oncology Research Training Fellow. Karyn A. Goodman participates in Viewray Data Safety Monitoring Board, RenovoRx Advisory Board, and Philips Advisory Board; and she is a cochair of National Cancer Institute Gastrointestinal Steering Committee. The remaining authors declare that they have no conflict of interest., (© 2024 The Author(s).)

Importance: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections., Competing Interests: S.A. is a current employee of Nestle Health Sciences. T.M. is currently funded through Stellus Rx and has participated in scientific advisory boards for AbbVie Inc. and Basilea Pharmaceutica. J.A. is a speaker for Shionogi Inc. M.A.K. is a speaker for Tetraphase. M.P.V. received research funding from Paratek Pharmaceuticals, Cumberland Pharmaceuticals, NIAID, and advisory Boards for Ferring Pharmaceuticals, Melinta Therapeutics, and Merck & Co. K.C.M. has consulted for Shionogi. B.M.J. has participated in speaking bureaus for Abbvie, La Jolla, and Paratek. A.L.V.H. has participated in speaking bureaus and has received research funding from Tetraphase. M.J.R. has received research and consulting from or participated in speaking bureaus for Abbvie, Melinta, Merck, Paratek, Shionogi, T2 Biosystems, and Tetraphase (La Jolla). All other authors declare no conflict of interest.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. The views and opinions expressed in this paper represent those of the authors and do not necessarily reflect the position or policy of any previous, current, or potential future employer., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aims: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed., Methods and Results: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality., Conclusion: This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Head and neck squamous cell carcinoma (HNSCC) is a leading cause of morbidity and mortality globally. Despite significant advances in well-established treatment techniques, prognosis for advanced-stage HNSCC remains poor. Recent, accumulating evidence supports a role for immunotherapy in HNSCC treatment. Radiation therapy (RT), a standard treatment option for HNSCC, has immunomodulatory and immunostimulatory effects that may enhance the efficacy of immunotherapy. In several cancer types, combining RT and immunotherapy has been shown to improve tumor response rates, increase survival, and reduce toxicity compared to traditional chemotherapy and radiation therapy. This review provides a timely overview of the current knowledge on the use of RT and immunotherapy for treating HNSCC. It highlights the potential advantages of combining these therapies, such as improved tumor response rates, increased survival, and reduced toxicity. The review also discusses the challenges that need to be addressed when redefining the standard of care in HNSCC, and proposes further research to optimize treatment combinations, minimize radiation-induced toxicity, and identify suitable patient populations for treatment.

Purpose: Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases, particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting., Methods and Materials: Patients with brain metastases from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Time-to-event analyses were conducted for any grade RN and symptomatic RN (SRN) with death incorporated as a competing risk. As a secondary analysis, recursive partitioning analysis (RPA) was used for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. Brain V12 Gy thresholds identified on RPA were then incorporated into the competing risks analysis. Concurrent SRS and ICI administration., Results: Six hundred fifty-seven patients with 4182 brain metastases across 11 international institutions were analyzed. The median follow-up for all patients was 13.4 months. The median follow-up was 12.8 months and 14.1 months for the concurrent and nonconcurrent groups, respectively (P = .03). The median patient age was 66 years, and the median Karnofsky Performance Status was 90. In patients with any grade RN, 1- and 2-year rates were 6.4% and 9.9%, respectively. In patients with SRN, 1- and 2-year rates were 4.8% and 7.2%, respectively. On RPA, the highest-fidelity models consistently identified V12 Gy as the dominant variable predictive of RN. Three risk groups were identified by V12 Gy: (1) < 12 cm 3 ; (2) 20 cm 3 ≥ V12 Gy ≥ 12 cm 3 ; (3) V12 Gy > 20 cm 3 . In patients with any grade RN, 1-year rates were 3.7% (V12 Gy < 12 cm 3 ), 10.3% (20 cm 3 ≥ V12 Gy ≥ 12 cm 3 ), and 12.6% (V12 Gy > 20 cm 3 ); the 2-year rates were 7.5% (V12 Gy < 12 cm 3 ), 13.8% (20 cm 3 ≥ V12 Gy ≥ 12 cm 3 ), and 15.4% (V12 Gy > 20 cm 3 ) (P < 0.001). In patients with any SRN, 1-year rates were 2.4% (V12 Gy < 12 cm 3 ), 8.9% (20 cm 3 ≥ V12 Gy ≥ 12 cm 3 ), and 10.3% (V12 Gy > 20 cm 3 ); the 2-year rates were 4.4% (V12 Gy < 12 cm 3 ), 12.4% (20 cm 3 ≥ V12 Gy ≥ 12 cm 3 ), and 13.1% (V12 Gy > 20 cm 3 ; P < 0.001). There were no statistically significant differences in rates of any grade RN or SRN when accounting for therapy timing for all patients and by V12 risk group identified on RPA., Conclusions: The use of SRS and ICI results in a low risk of any grade RN and SRN. This risk is not increased with concurrent administration. Therefore, ICI can safely be administered within 4-weeks of SRS. Three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mast cells and degranulation of preformed inflammatory mediators contribute to lower urinary tract symptoms. This study investigated pathways by which the mast cell stimulator compound 48/80 alters urinary bladder smooth muscle contractility via mast cell activation. We hypothesized that 1 ) mast cell degranulation causes spontaneous urinary bladder smooth muscle contractions and 2 ) these contractions are caused by urothelium-derived PGE 2 . Urothelium-intact and -denuded urinary bladder strips were collected from mast cell-sufficient (C57Bl/6) and mast cell-deficient (B6.Cg-Kit w-sh ) mice to determine if compound 48/80 altered urinary bladder smooth muscle (UBSM) contractility. Electrical field stimulation was used to assess the effects of compound 48/80 on nerve-evoked contractions. Antagonists/inhibitors were used to identify prostanoid signaling pathways activated or if direct activation of nerves was involved. Compound 48/80 caused slow-developing contractions, increased phasic activity, and augmented nerve-evoked responses in both mast cell-sufficient and -deficient mice. Nerve blockade had no effect on these responses; however, they were eliminated by removing the urothelium. Blockade of P2 purinoreceptors, cyclooxygenases, or G protein signaling abolished compound 48/80 responses. However, only combined blockade of PGE 2 (EP1), PGF 2α (FP), and thromboxane A 2 (TP) receptors inhibited compound 48/80-induced responses. Thus, the effects of compound 48/80 are urothelium dependent but independent of mast cells. Furthermore, these effects are mediated by druggable inflammatory pathways that may be used to manage inflammatory nonneurogenic bladder hyperactivity. Finally, these data strongly suggest that great care must be taken when using compound 48/80 to determine mast cell-dependent responses in the urinary bladder. NEW & NOTEWORTHY Urothelial cells are first responders to noxious contents of the urine. Our study demonstrates that the urothelium is not only a barrier but also a modulator of urinary bladder smooth muscle phasic activity and contractility independent of immune cell recruitment in response to an inflammatory insult.

Introduction: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is common in the intensive care unit (ICU) and is associated with significant morbidity and mortality. Continuous RRT (CRRT) non-selectively removes large amounts of amino acids from plasma, lowering serum amino acid concentrations and potentially depleting total-body amino acid stores. Therefore, the morbidity and mortality associated with AKI-RRT may be partly mediated through accelerated skeletal muscle atrophy and resulting muscle weakness. However, the impact of AKI-RRT on skeletal muscle mass and function during and following critical illness remains unknown. We hypothesise that patients with AKI-RRT have higher degrees of acute muscle loss than patients without AKI-RRT and that AKI-RRT survivors are less likely to recover muscle mass and function when compared with other ICU survivors., Methods and Analysis: This protocol describes a prospective, multicentre, observational trial assessing skeletal muscle size, quality and function in ICU patients with AKI-RRT. We will perform musculoskeletal ultrasound to longitudinally evaluate rectus femoris size and quality at baseline (within 48 hours of CRRT initiation), day 3, day 7 or at ICU discharge, at hospital discharge, and 1-3 months postdischarge. Additional skeletal muscle and physical function tests will be performed at hospital discharge and postdischarge follow-up. We will analyse the effect of AKI-RRT by comparing the findings in enrolled subjects to historical controls of critically ill patients without AKI-RRT using multivariable modelling., Ethics and Dissemination: We anticipate our study will reveal that AKI-RRT is associated with greater degrees of muscle loss and dysfunction along with impaired postdischarge recovery of physical function. These findings could impact the in-hospital and postdischarge treatment plan for these patients to include focused attention on muscle strength and function. We intend to disseminate findings to participants, healthcare professionals, the public and other relevant groups via conference presentation and publication without any publication restrictions., Trial Registration Number: NCT05287204., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective(s): There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature., Methods: A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage., Results: Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p = 0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p = 0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n = 7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p = 0.004) and the advanced stage was a predictor of DSS (p = 0.03)., Conclusions: Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort., Level of Evidence: 3 Laryngoscope, 133:1110-1121, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Sweat bees have repeatedly gained and lost eusociality, a transition from individual to group reproduction. Here we generate chromosome-length genome assemblies for 17 species and identify genomic signatures of evolutionary trade-offs associated with transitions between social and solitary living. Both young genes and regulatory regions show enrichment for these molecular patterns. We also identify loci that show evidence of complementary signals of positive and relaxed selection linked specifically to the convergent gains and losses of eusociality in sweat bees. This includes two pleiotropic proteins that bind and transport juvenile hormone (JH)-a key regulator of insect development and reproduction. We find that one of these proteins is primarily expressed in subperineurial glial cells that form the insect blood-brain barrier and that brain levels of JH vary by sociality. Our findings are consistent with a role of JH in modulating social behaviour and suggest that eusocial evolution was facilitated by alteration of the proteins that bind and transport JH, revealing how an ancestral developmental hormone may have been co-opted during one of life's major transitions. More broadly, our results highlight how evolutionary trade-offs have structured the molecular basis of eusociality in these bees and demonstrate how both directional selection and release from constraint can shape trait evolution., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The clinical and financial consequences associated with a penicillin-allergy label are increasingly evident and have garnered support from international organizations to prioritize penicillin-allergy delabelling programmes. Most settings lack access to resources including drug allergy specialists and rely on general practitioners (GPs) and pharmacists., Objectives: The aim of this scoping review was to identify and describe freely available penicillin-allergy delabelling materials to guide clinicians practising in resource-limited settings with initiative application., Methods: This scoping review searched two grey literature databases, six targeted websites and consulted content experts to identify freely available materials in the English language that provided evidence-based and actionable penicillin-allergy delabelling strategies. Study investigators ranked and voted on which screened resources should be included in the final review. Characteristics of resources were evaluated and compared., Results: Out of 1191 total citations, 6 open-access resources were included. Penicillin-allergy toolkits featuring various delabelling strategies were identified in four resources. The toolkits supported a broad range of downloadable and adaptable materials, predominantly targeted towards GPs. Patient educational materials were also provided. Another resource highlighted a point-of-care penicillin-allergy risk assessment calculator via a free mobile app that quickly and accurately identified low-risk penicillin-allergic patients. The final resource, a supplemental instructional video, presented impactful and standardized delabelling strategies that clinicians can adopt into daily practices., Conclusions: Limited penicillin-allergy delabelling materials are available in the grey literature but existing resources provide broad and diverse opportunities. Additional support from health protection agencies is critical to augment ongoing delabelling efforts., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Barcode-based tracking of individuals is revolutionizing animal behavior studies, but further progress hinges on whether in addition to determining an individual's location, specific behaviors can be identified and monitored. We achieve this goal using information from the barcodes to identify tightly bounded image regions that potentially show the behavior of interest. These image regions are then analyzed with convolutional neural networks to verify that the behavior occurred. When applied to a challenging test case, detecting social liquid transfer (trophallaxis) in the honey bee hive, this approach yielded a 67% higher sensitivity and an 11% lower error rate than the best detector for honey bee trophallaxis so far. We were furthermore able to automatically detect whether a bee donates or receives liquid, which previously required manual observations. By applying our trophallaxis detector to recordings from three honey bee colonies and performing simulations, we discovered that liquid exchanges among bees generate two distinct social networks with different transmission capabilities. Finally, we demonstrate that our approach generalizes to detecting other specific behaviors. We envision that its broad application will enable automatic, high-resolution behavioral studies that address a broad range of previously intractable questions in evolutionary biology, ethology, neuroscience, and molecular biology., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Melanoma brain metastases are commonly treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs). However, the toxicity of these 2 treatments is largely unknown when administered concurrently., Objective: To evaluate the risk of radiation necrosis (RN) with concurrent and nonconcurrent SRS and ICIs., Methods: The guidelines from the Strengthening the Reporting of Observational Studies in Epidemiology checklist were used. Inverse probability of treatment weighting, univariable and multivariable logistic regression, and the Kaplan-Meier method was utilized., Results: There were 203 patients with 1388 brain metastases across 11 international institutions in 4 countries with a median follow-up of 15.6 months. The rates of symptomatic RN were 9.4% and 8.2% in the concurrent and nonconcurrent groups, respectively ( P =.766). On multivariable logistic regression, V12 ≥ 10 cm 3 (odds ratio [OR]: 2.76; P =.006) and presence of BRAF mutation (OR: 2.20; P =.040) were associated with an increased risk of developing symptomatic RN; the use of concurrent over nonconcurrent therapy was not associated with an increased risk (OR: 1.06; P =.877). There were 20 grade 3 toxic events reported, and no grade 4 events reported. One patient experienced a grade 5 intracranial hemorrhage. The median overall survival was 36.1 and 19.8 months for the concurrent and nonconcurrent groups (log-rank P =.051), respectively., Conclusion: Concurrent administration of ICIs and SRS are not associated with an increased risk of RN. Tumors harboring BRAF mutation, or perhaps prior exposure to targeted agents, may increase this risk. Radiosurgical optimization to maintain V12 < 10 cm 3 is a potential strategy to reduce the risk of RN., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Purpose: There is a paucity of data regarding dalbavancin use in patients with a vancomycin allergy because of potential cross-reactivity between the 2 glycopeptide antibiotics., Methods: A retrospective medical record review was performed between February 2016 and February 2021 in patients with a listed vancomycin allergy who received dalbavancin as an outpatient infusion and had a listed vancomycin allergy in the electronic health record., Findings: There were 559 unique patients during the study period who received dalbavancin as an outpatient infusion, 10 of whom had a documented vancomycin allergy in the electronic health record. Four of the 10 patients had a history of a type I IgE-mediated reaction to vancomycin, 1 patient reported delayed rash, 2 patients reported a vancomycin infusion reaction, 2 patients reported acute kidney injury, and 1 patient reported intolerance with general malaise. All 10 patients received at least 1 dose of dalbavancin with no reported adverse events., Implications: This case series displays that all patients who received dalbavancin tolerated the infusion well with no adverse events reported. Dalbavancin may be a viable option for patients with a listed vancomycin allergy., Competing Interests: Declaration of Interest Bruce M. Jones has served on the speaker's bureau for AbbVie, Paratek, and La Jolla and performed consulting for Merck and Melinta. Kerry O. Cleveland has served on speaker's bureau for AbbVie, Cumberland, Merck, Paratek, and Pfizer. Christopher M. Bland has served on the speaker's bureau for Merck. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: It is well-documented that gender disparities exist in academic radiation oncology departments. The purpose of this study was to analyze gender differences in research productivity during residency among recent graduates of radiation oncology training programs in the United States (US)., Methods and Materials: We used several publicly available sources to create a database of US radiation oncology residents who graduated between 2015 and 2019. We systematically collected gender information from the National Plan and Provider Enumeration System National Provider Identifier Registry and Medicare claims registry. Postresidency employment information was collected using several publicly available sources. PubMed was queried to identify first-author publications of residents. A secondary analysis of metadata including impact factor, number of citations, modified Hirsch index ( h index), and type of publication was performed. A multivariable linear regression was performed to evaluate the effect of gender on research productivity during residency., Results: There were 910 total graduates identified during this period and who were entered into this database, of whom all had available gender information. Female trainees comprised 29.0% (n = 264) of RO residents and had fewer first-author publications and citations, had lower mean modified h index, and were published in journals with lower impact factors. On multivariable linear regression analysis, female gender was independently associated with decreased total number of publications ( P  = .005), mean number of citations ( P < .001), and modified h index ( P  = .001) when controlling for residency size and advanced (PhD or master's) degrees., Conclusions: In the US, female RO trainees had lower research productivity, which was not explained by advanced degrees or residency size. A significant gender gap in trainee research productivity persists, which has known implications in terms of academic achievement, promotions, and career trajectory. Future interventions to improve resident research productivity and mentorship are warranted., (© 2022 The Authors.)

Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs) are widely used in the management of brain metastases. These therapies are commonly administered concurrently; as SRS may enhance anti-tumor immunity and responsiveness to ICIs. However, the use of ICIs with and without SRS in the management of primary brain tumors remains a controversial topic. Meningiomas are the most common nonmalignant and extra-parenchymal brain tumor, which often respond well to surgery and radiotherapy. However, higher grade meningiomas tend to be resistant to these treatments, and the use of chemotherapy and targeted agents in this setting have yielded disappointing results. Thus, there is heightened interest in the utilization of ICIs. Glioblastoma is the most common malignant primary intraparenchymal brain tumor. It is associated with a grim prognosis with a median overall survival of approximately 20 months, despite optimal therapy. While SRS in the adjuvant setting, and ICI in the recurrent setting, have failed to demonstrate a survival benefit, SRS in the preoperative setting has the potential to enhance anti-tumor immunity and responsiveness to ICIs. Thus, these treatments represent an attractive option to add to the armamentarium of meningioma and glioblastoma management. In this review, we provide a detailed overview of the evidence supporting the use of ICIs and SRS in each of these settings.

Purpose: While a rising share of scientific research articles are being published in open access (OA) journals, their impact on resident research in radiation oncology is unknown. Thus, we sought to determine the number, content, and costs of first-author, PubMed-searchable articles radiation oncology residents in the United States (US) published in OA journals in recent years., Methods and Materials: We built a database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019. We then classified each journal in which these articles appeared as either OA or non-OA and obtained the current article-processing charge (APC) for each publication that appeared in an OA journal., Results: The residents in this study published 2637 first-author, PubMed-searchable articles, 555 of which (21.0%) appeared in 138 OA journals. The number of publications in OA journals per resident increased from 0.47 for the class of 2015 to 0.79 for the class of 2019. Publications in OA journals garnered fewer citations than those in non-OA journals (8.9 vs 14.9, P < .01). Furthermore, 90.6% of OA journals levy an APC for original research reports (median, $1896), which is positively correlated with their 2019 impact factor ( r  = 0.63, P < .01). Aggregate APCs totaled $900,319.21 and appeared to increase over the study period., Conclusions: The number of first-author, PubMed-searchable articles published by graduating US radiation oncology residents in OA journals rose significantly between 2015 and 2019. To maximize the benefits of OA publishing in the future, US radiation oncology residents will need to ensure that they use vetted OA journals to publish their research findings and avoid predatory journals., (© 2022 The Author(s).)

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related, peer-reviewed literature that detailed an "actionable" intervention among hospitalized populations during 2021. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight "actionable" interventions used by antimicrobial stewardship programs in hospitalized populations to capture potentially effective strategies for local implementation., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Pharmacy residency recruitment and interviews have been significantly impacted by the COVID-19 pandemic. Many traditional recruitment events and interviews were transitioned from in-person to virtual, and new approaches to recruitment, such as virtual open houses, were developed. There are limited data on how these changes impacted pharmacy residency applicants and programs, and the future of virtual events is currently unknown. We highlight recommendations for virtual recruitment and interviews and provide suggestions for residency programs and national organizations to improve virtual processes in the future., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose: For childhood sexual abuse survivors, cancer care can be retraumatizing because of perceived similarities to the original sexual violence. The authors' group designed and implemented a sensitive practice tool (SPT) and evaluated the feasibility of the tool in female patients receiving breast radiation., Methods: The SPT was offered as a "universal precaution" to patients with breast cancer as part of standard clinical care. Patients were given the SPT, which included an instructional video about radiotherapy and a survey about triggers and preferences. The survey results were provided to radiation therapists and used to personalize patients' care. A retrospective chart review and quality improvement survey of therapists were performed., Results: Of 739 eligible patients, 493 (66.7%) completed the SPT from November 2013 to June 2019. Among respondents, 281 (57.0%) reported potential triggers, 395 (80.1%) reported distress management preferences, and 59 (12.0%) requested psychosocial referrals. Mean patient satisfaction was high, and a majority of patients were likely to recommend the SPT to other patients (85.3%). Among radiation therapists (n = 13), 100% reported that the SPT made it easier to customize or individualize patient care. Trauma disclosure was not significantly associated with increased frequency of trigger endorsement (P = .07) but was associated with increased endorsement of distress management preferences (P = .02) and psychosocial referral requests (P < .001)., Conclusions: The reported experience with the SPT in the breast radiotherapy setting demonstrated that potential triggers and distress management preferences among patients are common and that patient satisfaction with the SPT is high, yielding clinically meaningful and actionable sensitive practice information., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival., Methods: This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required., Results: The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test)., Conclusions: TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

Introduction: Due to the COVID-19 pandemic, most pharmacy residency programs changed to an all-virtual format for recruitment and interviews for the 2020-2021 application cycle. There are no data evaluating the experiences and perceptions of these changes from the perspective of pharmacy residency programs and applicants., Methods: An electronic cross-sectional survey was distributed via email to post-graduate year 1 (PGY1) and post-graduate year 2 (PGY2) pharmacy residency programs and applicants across the Southeastern United States. Results have been reported according to the Checklist for Reporting of Survey Studies (CROSS) guidelines (Enhancing the QUAlity and Transparency Of health Research [EQUATOR] Network)., Results: 142 residency applicants and 104 residency programs responded to the survey. Most respondents participated in virtual recruitment and interviews. In 2020-2021, less residency programs participated in local/regional showcases and personal placement services, but social media engagement increased. Of the applicants who responded, over half felt the need to apply to more programs during this application cycle, and a corresponding increase in applications were seen by residency programs. Residency interviews appeared shorter than previous years, and less programs offered an informal time to get to know the applicants. Overall, applicants and residency programs preferred on-site interviews, but both parties reported feeling confident creating rank lists after virtual interviews., Conclusion: These results highlight the impact of COVID-19 on residency recruitment and the interview process. Residency programs should implement feedback for improving the virtual experience, as able. The ongoing pandemic may affect the 2022-2023 application cycle, and pharmacy leadership organizations should consider developing guidance for applicants and residency programs on navigating another year of virtual events.This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques., Competing Interests: PB reports contribution to UpToDate outside of the submitted work. JW is on the advisory board of Bayer, he serves as a consultant to Angiochem, Bayer, Juno, Novocure, Vanquish Oncology, and GT Medical technologies. JP reports research funding and honoraria from Varian and research funding from Genentech, NIH, and Kroger; he serves on the advisory board of Novocure. IM serves as a consultant to BrainLab and Integra; DT reports institutional support from Novocure Ltd and consulting for Boston Scientific Corporation outside to the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lehrer, Jones, Dickstein, Green, Germano, Palmer, Laack, Brown, Gondi, Wefel, Sheehan and Trifiletti.)

Thirty percent of patients with head and neck squamous cell carcinoma (HNSCC) are at least 70 years of age. This number continues to rise as life expectancy continues to increase. Still, older adults with HNSCC remain underrepresented in clinical trials, resulting in ambiguity on optimal management. Older adults are a complex patient population, often requiring increased support due to issues relating to functional and performance status, medical comorbidities, and medication management. Furthermore, in older adults with HNSCC, many of these conditions are independently associated with increased toxicity and worse outcomes. Toxicity in the older adult remains difficult to predict and to understand, and as treatment decisions are based on treatment tolerability, it is essential to understand the toxicities and how to minimize them. Novel predictive scores are being developed specifically for older adults with HNSCC to understand toxicity and to assist in personalized treatment decisions. There are clinical trials presently underway that are investigating shortened radiation courses and novel, less toxic systemic treatments in this population. In the forthcoming sections, we provide a detailed overview of the clinical data, treatment paradigms, and considerations in this population. This review provides a comprehensive overview of existing clinical data and clinical considerations in the older adult head and neck cancer population. Additionally, we provide a detailed overview of pertinent current and ongoing clinical trials, as well as future areas for investigation.

With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods: We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center., (Copyright © 2021 Elsevier Inc. All rights reserved.)