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Objectives: The incidence of oropharyngeal cancer continues to rise in the United States, yet studies on the quality of life (QoL) of oropharyngeal cancer patients are limited. The objective of this pilot study was to assess the impact of oral health on the QoL in oropharyngeal cancer survivors., Materials and Methods: Oropharyngeal cancer survivors with a confirmed cancer diagnosis from 1996 to 2016 were sampled from the Utah Cancer Registry. The Oral Health Impact Profile-14 (OHIP-14) questionnaire was administrated between January and May of 2019. The impact of oral health on QoL was evaluated using simple linear regression (β-coefficient)., Results: Among the 260 oropharyngeal cancer survivors, the majority were male (84.6 %) and ≥ 60 years of age at the time of cancer diagnosis (74.0 %). The most frequently reported symptoms of OHIP-14 were discomfort while eating any foods (19.2 %) and worsening sense of taste (16.0 %). The overall OHIP-14 mean score was 13.3. Significantly worse OHIP-14 scores were observed for females (β = 12.85, p = 0.01), chemotherapy recipients (β = 6.60, p = 0.02), and past smokers (β = 5.25, p = 0.04). Better OHIP-14 scores (better oral QoL) were observed in patients with distant cancer stage (β = -7.66, p = 0.01), higher income (β = -2.50, p = 0.05), and older age at cancer diagnosis (β = -0.35, p = 0.03)., Conclusion: The oral health-related quality of life scores observed in this pilot study suggest a need for improvement in patient symptom management over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The faradaic efficiency (FE) of the electrochemical hydrogenation (ECH) of phenol and other biomass-derived model compounds could potentially be improved by operating in alkaline electrolytes, where the parasitic hydrogen evolution reaction rate is significantly slower due to a higher Volmer step barrier. However, this approach is potentially limited by the impact of the higher barrier for adsorbed hydrogen (H ad ) formation, as hydrocarbon ECH is expected to be limited by a hydrogen atom transfer, progressing through a Langmuir-Hinshelwood-type (LH) mechanism. In this work, we show that there are contrasting pH trends for phenol ECH between Pt and Rh, two common catalysts for ECH reactions. Phenol ECH FE and rate on Pt is highest in acidic electrolytes of pH ≤ 5, while activity on Rh is highest near pH 9-10. While our kinetic analysis supports a LH mechanism for Pt at all pH, phenol ECH on Rh shifts from a LH mechanism at low pH to being limited by a direct proton-coupled electron transfer (Eley-Rideal-type mechanism) in which surface adsorbed phenol is hydrogenated by solution-phase H-transfer. We show that the peak activity on Rh at pH 9-10 is due to the proximity of the pH to the p K a of phenol (p K a = 10.0). The reversibility of protonation/deprotonation of phenol when electrolyte pH matches its p K a helps to mediate H-transfer from solution to adsorbed phenol. We also discuss the role of buffer species in mitigating the local pH change and as a H-donor in phenol ECH on Rh at alkaline pH., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components., Purpose: To apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R 2 */R 2 ' /QSM., Study Type: Longitudinal, prospective., Subjects: Twenty relapsing-remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years)., Field Strength/sequence: Three-dimensional multiple echo gradient echo (QSM and R 2 * mapping), two-dimensional dual echo fast spin echo (R 2 mapping), T 2 -weighted fluid attenuated inversion recovery, and T1-weighted magnetization prepared gradient echo sequences at 3 T., Assessment: Data were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid-attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R 2 * or separated into positive/negative components from χ separation., Statistical Tests: Two-sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R 2 */R 2 ' /QSM. Significant level: P < 0.005., Results: A total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R 2 */R 2 ' . When lesions were grouped based on changes in QSM and R 2 *, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility-sensitive MRI indices and χ separation., Data Conclusion: Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R 2 * and QSM alone., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs). We found evidence of local retinoic acid (RA) generation in both human leptomeningeal metastasis and mouse models in the form of elevated spinal fluid retinol and expression of RA-generating dehydrogenases within the leptomeningeal microenvironment. Stimulating LeptoM cells with RA induced expression of transcripts encoding de novo fatty acid synthesis pathway enzymes in vitro . In vivo , while deletion of Stra6 did not alter cancer cell leptomeningeal growth, knockout of Rxra/b/g interrupted cancer cell lipid biosynthesis and arrested cancer growth. These observations illustrate a mechanism whereby metastatic cancer cells awake locally-generated developmental cues for metabolically reprograming, suggesting novel therapeutic approaches.

Background: Recent approvals of chimeric antigen receptor T-cells (CAR T) and bispecific antibody therapies offer new hope for relapsed refractory multiple myeloma (RRMM) patients, with superior efficacy over standard regimens observed in clinical trials. However, relapse after BCMA-directed therapy is common and requires further investigation., Patients and Methods: We conducted a retrospective cohort study on 57 RRMM patients treated with BCMA-directed CAR T. Only the patients who had an initial response and lost BCMA-expressing identified PC following CAR T infusion at Day 30 were included in the analysis. Multicolor flow cytometry (MFC) to detect BCMA + plasma cell (PC) re-emergence was performed on bone marrow samples at defined intervals and clinical responses were assessed using International Myeloma Working Group criteria., Results: The majority of patients achieved undetectable BCMA on MFC postinfusion, with subsequent BCMA+ PC re-emergence observed in 55% of cases. Notably, 91% of patients experiencing clinical relapse showed BCMA+ PC re-emergence, often preceding relapse. Early relapse (<6 months) was associated with earlier BCMA re-emergence., Conclusion: Early BCMA+ PC re-emergence may serve as a prognostic marker for clinical relapse post-BCMA CAR T therapy. Monitoring BCMA+ PC levels via MFC offers potential for early relapse detection and informed treatment decisions. Further studies, including novel BCMA-directed minimal residual disease (MRD) detection technologies, are warranted to validate these findings and refine RRMM management strategies., Competing Interests: Disclosure The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nausheen Ahmed reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Nausheen Ahmed reports a relationship with Legend Biotech that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Envision Pharma Inc that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Novartis that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Legend Biotech that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Nektar Therapeutics that includes: consulting or advisory. Nausheen Ahmed reports a relationship with Kite Pharma Inc that includes: consulting or advisory, nonfinancial support, and travel reimbursement. Joseph P McGuirk reports a relationship with Autolus Ltd that includes: consulting or advisory. Joseph P McGuirk reports a relationship with CRISPR Therapeutics that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Kite Pharma Inc that includes: consulting or advisory. Joseph P McGuirk reports a relationship with CARGO Therapeutics, Inc. that includes: consulting or advisory. Joseph P McGuirk reports a relationship with Caribou Biosciences Inc that includes: consulting or advisory. Leyla Shune reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. Leyla Shune reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: This review examines health care team-focused interventions on managing persistent or recurrent distress behaviors among older adults in long-term residential or inpatient health care settings., Methods: We searched interventions addressing health care worker (HCW) knowledge and skills related to distress behavior management using Ovid MEDLINE, Elsevier Embase, and Ovid PsycINFO from December 2002 through December 2022., Results: We screened 6,582 articles; 29 randomized trials met inclusion criteria. Three studies on patient-facing HCW interactions (e.g. medication management, diagnosing distress) showed mixed results on agitation; one study found no effect on quality of life. Six HCW-focused studies suggested short-term reduction in distress behaviors. Quality-of-life improvement or decreased antipsychotic use was not evidenced. Among 17 interventions combining HCW-focused and patient-facing activities, 0 showed significant distress reduction, 8 showed significant antipsychotic reduction (OR = 0.79, 95%CI [0.69, 0.91]) and 9 showed quality of life improvements (SMD = 0.71, 95%CI [0.39, 1.04]). One study evaluating HCW, patient-, and environmental-focused intervention activities showed short-term improvement in agitation., Conclusions and Clinical Implications: Novel health care models combining HCW training and patient management improve patient quality of life, reduce antipsychotic use, and may reduce distress behaviors. Evaluation of intervention's effects on staff burnout and utilization is needed.

Background: The current landscape of organ donation and transplantation (ODT) registries is not well established. This narrative review sought to identify and characterize the coverage, structure, and data capture of ODT registries globally., Methods: We conducted a literature search using Ovid Medline and web searches to identify ODT registries from 2000 to 2023. A list of ODT registries was compiled based on publications of registry design, studies, and reports. Extracted data elements included operational features of registries and the types of donor and recipient data captured., Results: We identified 129 registries encompassing patients from all continents except Antarctica. Most registries were active, received funding from government or professional societies, were national in scope, included both adult and pediatric patients, and reported patient-level data. Registries included kidney (n = 99), pancreas (n = 32), liver (n = 44), heart (n = 35), lung (n = 30), intestine (n = 15), and islet cell (n = 5) transplants. Most registries captured donor data (including living versus deceased) and recipient features (including demographics, cause of organ failure, and posttransplant outcomes) but there was underreporting of other domains (eg, donor comorbidities, deceased donor referral rates, waitlist statistics)., Conclusions: This review highlights existing ODT registries globally and serves as a call for increased visibility and transparency in data management and reporting practices. We propose that standards for ODT registries, a common data model, and technical platforms for collaboration, will enable a high-functioning global ODT system responsive to the needs of transplant candidates, recipients, and donors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Natriuretic peptide testing is guideline recommended as an aid to the diagnosis of heart failure (HF). We sought to evaluate the performance of the ADVIA Centaur (Siemens Healthcare Diagnostics, Tarrytown, NY) NT-proBNPII assay (PBNPII) in emergency department (ED) dyspneic patients., Methods: Eligible patients presented to the ED with dyspnea, with their gold standard diagnosis determined by up to 3 cardiologists blinded to the PBNPII results. Patients were stratified into 3 groups based on PBNPII resultsa rule out group of NT-proBNP<300  pg/mL, an age-specific rule in group using cutoffs of 450, 900, and 1800 pg/mL, for <50, 50-75, and > 75 years respectively, and an intermediate cohort for results between the rule out and rule in groups., Results: Of 3128 eligible patients, 1148 (36.7 %) were adjudicated as acute heart failure (AHF). The gold standard AHF diagnosis rate was 3.7, 24.3, and 67.2 % for patients with NTproBNPII in the negative, indeterminate, and positive groups, respectively. Overall likelihood ratios (LR) were 0.07 (95 % CI: 0.05,0.09), 0.55 (0.45,0.67), and 3.53 (3.26,3.83) for the same groups, respectively. Individual LR+for age dependent cutoffs were 5.01 (4.25,5.91), 3.71 (3.25,4.24), and 2.38 (2.10,2.69), respectively. NTproBNPII increased with increasing severity of HF when stratified by NYHA classification., Conclusions: The ADVIA Centaur PBNPII assay demonstrates acceptable clinical performance using the recommended single rule out and age dependent rule in cutoffs for an AHF diagnosis in dyspneic ED patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Peacock has received research grants from Abbott, Brainbox, Quidel, Roche, Siemens; served as a consultant for Abbott, Astra-Zeneca, Brainbox, Bristol Meyers Squibb, Instrument Labs, Janssen, Osler, Quidel, Roche, Siemens, Spinchip, CSL-Vifor; and has stock/ownership interests in AseptiScope Inc, Brainbox Inc, Braincheck Inc, Coagulo Inc, Comprehensive Research Associates LLC, Comprehensive Research Management Inc, Emergencies in Medicine LLC, Lucia Inc, Prevencio Inc, RCE Technologies, ROMTech, ScPharma, Trivirum Inc, and Upstream Inc.Dr. Januzzi is supported in part by the Hutter Family Professorship; has received grant support from Abbott, Cleveland Heart Labs, Siemens, Singulex, and Prevencio; has received consulting income from Roche Diagnostics, Critical Diagnostics, Sphingotec, Phillips, and Novartis; and has participated in clinical endpoint committees/data or safety monitoring boards for Novartis, Amgen, GE, Janssen, Pfizer, and Boehringer Ingelheim. J Snyder, C Brown, Y Liu, and CK Cooper are or were full-time employees of Siemens Healthcare Diagnostics and have no competing interests to declare]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Three critically ill, chemotherapy-refractory patients with diffuse large B-cell lymphoma (DLBCL) received loncastuximab tesirine in conjunction with standard therapies for secondary malignancy-associated hemophagocytic lymphohistiocytosis (Mal-HLH). All patients were treated inpatient, with one requiring intubation on the day of administration. Each patient had an H-score >238, indicating a >98% probability of HLH. A significant reduction in ferritin levels was observed in two patients, and one patient achieved a complete response (CR). Loncastuximab tesirine demonstrated promise in managing Mal-HLH where previous treatments had failed. This study suggests that loncastuximab tesirine exhibits favorable activity and should be considered a valuable addition to the treatment options for Mal-HLH driven by DLBCL., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Schieber et al.)

Spectrum of care (SOC) has recently been described in the literature, yet it is not an entirely new concept within the veterinary profession. Practitioners in general veterinary practice have long needed to provide a broad range of unique care options for their patients and clients, particularly those for whom referral is not possible. More recently, graduates and their employers have reported that new veterinarians often lack the competence and confidence to provide a broad array of care options, while training in ever more specialized tertiary-referral environments. To better prepare veterinary learners to cope with the variable nature of general veterinary practice and to better meet employer demands, The Ohio State University College of Veterinary Medicine purposefully backward designed learning experiences in a new outcomes-based curriculum so that SOC is emphasized and aligned with the foundation offered by the Competency-Based Veterinary Education (CBVE) model. A unique set of subcompetencies and educational goals were collaboratively developed and used to define a new final year rotation, with additional input provided by an advisory panel of practicing SOC veterinarians from private practice. Ideal caseload characteristics, case numbers, appointment length, daily activities, and other elements were defined, and final year student performance was monitored during implementation to assess progress in meeting key developmental milestones. Incorporating spectrum of care training at The Ohio State University shows promise for developing confidence and competence in new graduates, while also increasing their skills, and perhaps improving their mental health.

Background: The number of living kidney donors in the United States has declined since 2005, with variations based on the donor-recipient relationship. The reasons for this decline are unclear, and strategies to mitigate declined donations remain elusive. We examined the change in donor number monthly (within-year) versus annually (between-years) to inform potentially modifiable factors for future interventions., Methods: In this registry-based cohort analysis of 141 759 living kidney donors between 1995 and 2019, we used linear mixed-effects models for donor number per month and year to analyze between-year and within-year variation in donation. We used Poisson regression to quantify the change in the number of donors per season before and after 2005, stratified by donor-recipient relationship and zip-code household income tertile., Results: We observed a consistent summer surge in donations during June, July, and August. This surge was statistically significant for related donors (incidence rate ratio [IRR] range: 1.12-1.33) and unrelated donors (IRR range: 1.06-1.16) across donor income tertiles., Conclusion: Our findings indicate lower rates of living kidney donation in non-summer months across income tertiles. Interventions are needed to address barriers to donation in non-summer seasons and facilitate donations throughout the year. Since the Organ Donor Leave Law provides a solid foundation for supporting year-round donation, extending the law's provisions beyond federal employees may mitigate identified seasonal barriers., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Previous research on abortion-related crowdfunding campaigns found that they are impacted by stigma around abortion and rarely successful. This paper analyzes crowdfunding activity in the US following a leak of the Supreme Court decision in Dobbs. V. Jackson Women's Health Organization, a time period that saw increased financial support of abortion access funds. Crowdfunding campaigns that included "abort" or "abortion" and were created between May 2 and November 8, 2022 were recorded from the GoFundMe and GiveSendGo crowdfunding platforms. These campaigns were reviewed for whether they were US based and sought funding where abortion was used as a justification for support. Included campaigns were assigned a campaign recipient type: (1) Organizations providing abortion access; (2) Organizations seeking legal protection for abortion; (3) Individuals seeking abortion access; (4) Organizations seeking to reduce abortion access; and (5) Individuals with needs resulting from choosing not to access abortion. The authors also identified four types of rationale for supporting these campaigns. Following a leak of the Dobbs decision, 398 abortion-related crowdfunding campaigns in the US raised over $3.8 million from over 50,000 donations. Campaigns supporting abortion access organizations raised higher median amounts than organizations seeking to reduce abortion access. Individuals seeking abortion access raised higher median amounts than individuals who chose not to terminate a pregnancy. In a reversal from pre-Dobbs crowdfunding, abortion access campaigns tended to outperform other abortion-related campaigns. It is not clear how long-lived this change in support will be and campaigners remain vulnerable to changes in platforms' content moderation policies., (© 2024 University of Ottawa.)

Objective: Relapsed/refractory multiple myeloma (MM) has poor outcomes, especially in heavily pretreated patients. Limited data exists on the use of novel therapies in MM patients with renal dysfunction. This case series describes the successful initiation of teclistamab in four patients with heavily pre-treated MM on hemodialysis (HD)., Data Sources: The medical records of four adult MM patients on HD who received teclistamab were retrospectively reviewed., Data Summary: All patients completed teclistamab step-up dosing and received at least one full dose. HD runs were administered irrespective of teclistamab initiation. Patients tolerated therapy well, with only one patient experiencing grade 1 CRS, which was managed with supportive care., Conclusions: Due to the complexity of this patient population, close monitoring and multidisciplinary care are crucial. This approach is essential for effectively managing MM patients with renal dysfunction and for exploring novel treatment options.

The purpose of the present study was to examine how gaze and emotion processing may change due to differences in gender appearance and gender identity of the perceived face. We manipulated gender appearance (male or female), gender identity (cisgender or transgender), gaze direction (direct or averted), and expressed emotions (anger, fear, or neutral) of face models in an emotion rating task. We replicate several previous findings, including a direct gaze advantage, an emotion effect, and an interaction between gaze direction and expressed emotion. In line with previous findings on the influence of facial morphology for face processing, we found that male faces were more quickly and intensely perceived for displays of anger, while female faces were more quickly and intensely perceived for displays of fear. Of key interest, gender identity influenced face perception for different emotion expressions and gaze directions for ratings and reaction times in a variety of ways. For example, transgender male faces were seen as angrier and less fearful than cisgender male faces, while the opposite effect occurred for female faces. These results suggest that face perception is systematically shaped by morphological differences as well as more abstract social constructs related to gender identity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Complementary and alternative (CAM) cancer treatment is often expensive and not covered by insurance. As a result, many people turn to crowdfunding to access this treatment., Objective: The aim of this study is to identify the rationales of patients with cancer seeking CAM treatment abroad by looking specifically at crowdfunding campaigns to support CAM cancer treatment in Tijuana, Mexico., Methods: We scraped the GoFundMe.com and GiveSendGo.com crowdfunding platforms for campaigns referencing CAM cancer clinics in Tijuana, initiated between January 1, 2022, and February 28, 2023. The authors created a coding framework to identify rationales for seeking CAM treatment in Tijuana. To supplement campaign metadata, we coded the beneficiary's cancer stage, type, age, specific treatment sought, whether the beneficiary died, gender, and race., Results: Patients sought CAM cancer treatment in Tijuana because the (1) treatment offers the greatest efficacy (29.9%); (2) treatment offered domestically was not curative (23.2%); (3) the clinic treats the whole person, and addresses the spiritual dimension of the person (20.1%); (4) treatments are nontoxic, natural, or less invasive (18.2%); and (5) clinic offers the newest technology (8.5%). Campaigns raised US $5,275,268.37 and most campaign beneficiaries were women (69.7%) or White individuals (71.1%)., Conclusions: These campaigns spread problematic misinformation about the likely efficacy of CAM treatments, funnel money and endorsements to CAM clinics in Tijuana, and leave many campaigners short of the money needed to pay for CAM treatments while costing beneficiaries and their loved one's time, privacy, and dignity. This study affirms that Tijuana, Mexico, is a very popular destination for CAM cancer treatment., (©Jeremy Snyder, Marco Zenone, Ashmita Grewal, Timothy Caulfield. Originally published in JMIR Cancer (https://cancer.jmir.org), 14.08.2024.)

Purinergic P2X3 receptors form trimeric cation-gated channels, which are activated by extracellular ATP. P2X3 plays a crucial role in chronic cough and affects over 10% of the population. Despite considerable efforts to develop drugs targeting P2X3, the highly conserved structure within the P2X receptor family presents obstacles for achieving selectivity. Camlipixant, a potent and selective P2X3 antagonist, is currently in phase III clinical trials. However, the mechanisms underlying receptor desensitization, ion permeation, principles governing antagonism, and the structure of P2X3 when bound to camlipixant remain elusive. In this study, we established a stable cell line expressing homotrimeric P2X3 and utilized a peptide scaffold to purify the complex and determine its structure using cryo-electron microscopy (cryo-EM). P2X3 binds to camlipixant at a previously unidentified drug-binding site and functions as an allosteric inhibitor. Structure-activity studies combined with modeling and simulations have shed light on the mechanisms underlying the selective targeting and inhibition of P2X3 by camlipixant, distinguishing it from other members of the P2X receptor family., Competing Interests: Conflict of Interest declaration: PPN, SS, IH, SA, and JS work for ELANCO. This work was funded by a grant to RS by ELANCO.

Abstract: Blue sky thinking references the opportunity to brainstorm about a topic without limits… to consider what things might be like if creative thoughts were unconstrained by current philosophies or other boundaries. This article is a call to our fellow educators to consider how blue sky thinking applied to physician assistant (PA) program accreditation might further advance programs, faculty, and the profession. To develop and maintain a PA program, institutions must voluntarily undergo evaluation by the Accreditation Review Commission on Education for the Physician Assistant. Compliance with accreditation encourages sound educational practices, promotes program self-study, stimulates innovation, maintains confidence with the public, and focuses on continuous quality improvement. In addition, accreditation "can hold institutions accountable for desired outcomes and professional standards." Indeed, while the PA profession has promulgated across the globe, the 50+ years of graduating PAs educated with the highest quality education assures that the United States remains a gold standard. As the 5th edition of the standards are implemented and planning for the 6th edition is underway, in the spirit of continuous quality improvement, we encourage stakeholders of the PA profession to contemplate ways in which accreditation might continue to purposefully advance a desired future state for the profession. In this article, we draw on examples from other health professions which might inform a discussion around the future of PA accreditation. Specifically, the topics of a unified profession title and degree, a specific title and position for program leadership, a modification to how PA programs receive medical direction, and efforts to advance scholarship are addressed., Competing Interests: Trenton Honda is Editor in Chief of JPAE. The remaining authors declare no conflict of interest., (Copyright © 2024 PA Education Association.)

Jacoby and colleagues used an iterative rhythm reproduction paradigm with listeners from around the world to provide evidence for both rhythm universals (simple-integer ratios 1:1 and 2:1) and cross-cultural variation for specific rhythmic categories that can be linked to local music traditions in different regions of the world., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer., Patients and Methods: We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers., Results: Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality., Conclusion: Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: To accurately assess evidence from environmental and public health field trials, context and implementation details of the intervention must be weighed with trial results; yet these details are under and inconsistently reported for water, sanitation, and hygiene (WASH), limiting the external validity of the evidence., Methods: To quantify the level of reporting of context and implementation in WASH evaluations, we conducted a scoping review of the 40 most cited evaluations of WASH interventions published in the last 10 years (2012-2022). We applied criteria derived from a review of existing reporting guidance from other sectors including healthcare and implementation science. We subsequently reviewed main articles, supplements, protocols, and other associated resources to assess thoroughness of context and implementation reporting., Results: Of the final 25 reporting items we searched for, four-intervention name, approach, location, and temporality-were reported by all studies. Five items-theory, implementer qualifications, dose intensity, targeting, and measured fidelity-were not reported in over a third of reviewed articles. Only two studies (5%) reported all items in our checklist. Only 74% of items were found in the main article, while the rest were found in separate papers (7%) or not at all (19%)., Discussion: Inconsistent reporting of WASH implementation illustrates a major challenge in the sector. It is difficult to know what interventions are actually being evaluated and how to compare evaluation results. This inconsistent and incomplete implementation reporting limits the ability of programmers and policy makers to apply the available evidence to their contexts. Standardized reporting guidelines would improve the application of the evidence for WASH field evaluations., Competing Interests: Declaration of competing interest The authors declare they have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Pre-visit planning entails completing necessary tasks prior to clinic appointments. Community pharmacists (CPs) have unique knowledge about patients' medication use but do not routinely provide drug therapy reviews before clinic visits. Objectives: (1) Create and implement a business partnership between a CP and family medicine clinic (FMC) for CP provision of pre-visit medication reviews, and (2) describe the billing experience for shared patients in the FMC chronic care management (CCM) program. Methods: A prospective 8-month study in one community pharmacy and FMC in Iowa. Eligible patients were enrolled in the clinic CCM program and received their prescriptions at the CP. CPs were granted access to the clinic electronic health record (EHR), performed medication reviews, and recorded drug therapy recommendations (DTRs) in the clinic EHR. FMC physicians reviewed CP DTRs before the patient encounter. Time tracking software in the EHR recorded CP and FMC time performing CCM services. CCM revenue was prorated between parties. FMC physicians completed a survey about their experience. Results: Overall, there were 129 CP reviews performed for 95 patients. These reviews resulted in 169 DTRs and 76% were accepted by the physician. There were 71 CCM claims billed and CCM revenue was $3596 ($1796 FMC, $1800 CP). More than 90% of physicians (N = 11) indicated they reviewed CP DTRs before the patient encounter and agreed they were helpful to their practice. Conclusion: CPs completed pre-visit medication reviews and made accepted medication therapy recommendations. CCM billing provided a mechanism for CPs to receive revenue for their services., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A large proportion of potential organ donors are not utilized for kidney transplantation out of risk of early allograft loss because of donor-related characteristics. These can be summarized using kidney donor profile index (KDPI). Because KDPI affects the choice of the recipient, the predictive ability of KDPI is tied to recipient attributes. These have been questioned to explain most of the predictive ability of KDPI. This study aims to quantify the effect of the donor on early graft loss (EGL) by accounting for nonrandom allocation., Methods: This study included patients undergoing kidney transplantation from deceased donors between 2014 and 2020 from the Scientific Registry of Transplantation Recipients. EGL, defined as a return to dialysis or retransplantation during the first posttransplant year, was the primary endpoint. Nonrandom allocation and donor-recipient matching by KDPI necessitated the use of inverse probability treatment weighting, which served to assess the effect of KDPI and mitigate selection bias in a weighted Cox regression model., Results: The study comprised 89 290 transplantations in 88 720 individual patients. Inverse probability treatment weighting resulted in a good balance of recipient covariates across values of continuous KDPI. Weighted analysis showed KDPI to be a significant predictor for short-term outcomes. A comparable (in terms of age, time on dialysis, previous transplants, gender, diabetes status, computed panel-reactive antibodies, and HLA mismatches) average recipient, receiving a kidney from a donor with KDPI 40-60 had a 3.5% risk of EGL increased to a risk of 7.5% if received a kidney from a KDPI >95 donor (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7). However, for all-cause survival KDPI was less influential., Conclusions: The predictive ability of KDPI does not stem from recipient confounding alone. In this large sample-sized study, modeling methods accounting for nonindependence of recipient selection verify graft quality to effectively predict short-term transplantation outcomes., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

This study introduces an innovative strategy for the rapid and accurate identification of pesticide residues in agricultural products by combining surface-enhanced Raman spectroscopy (SERS) with a state-of-the-art transformer model, termed SERSFormer. Gold-silver core-shell nanoparticles were synthesized and served as high-performance SERS substrates, which possess well-defined structures, uniform dispersion, and a core-shell composition with an average diameter of 21.44 ± 4.02 nm, as characterized by TEM-EDS. SERSFormer employs sophisticated, task-specific data processing techniques and CNN embedders, powered by an architecture features weight-shared multi-head self-attention transformer encoder layers. The SERSFormer model demonstrated exceptional proficiency in qualitative analysis, successfully classifying six categories, including five pesticides (coumaphos, oxamyl, carbophenothion, thiabendazole, and phosmet) and a control group of spinach data, with 98.4% accuracy. For quantitative analysis, the model accurately predicted pesticide concentrations with a mean absolute error of 0.966, a mean squared error of 1.826, and an R 2 score of 0.849. This novel approach, which combines SERS with machine learning and is supported by robust transformer models, showcases the potential for real-time pesticide detection to improve food safety in the agricultural and food industries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The Philadelphia chromosome-negative myeloproliferative neoplasms are a group of slowly progressing haematological malignancies primarily characterised by an overproduction of myeloid blood cells. Patients are treated with various drugs, including the JAK1/2 inhibitor ruxolitinib. Mathematical modelling can help propose and test hypotheses of how the treatment works., Materials and Methods: We present an extension of the Cancitis model, which describes the development of myeloproliferative neoplasms and their interactions with inflammation, that explicitly models progenitor cells and can account for treatment with ruxolitinib through effects on the malignant stem cell response to cytokine signalling and the death rate of malignant progenitor cells. The model has been fitted to individual patients' data for the JAK2 V617F variant allele frequency from the COMFORT-II and RESPONSE studies for patients who had substantial reductions (20 percentage points or 90% of the baseline value) in their JAK2 V617F variant allele frequency ( n = 24 in total)., Results: The model fits very well to the patient data with an average root mean square error of 0.0249 (2.49%) when allowing ruxolitinib treatment to affect both malignant stem and progenitor cells. This average root mean square error is much lower than if allowing ruxolitinib treatment to affect only malignant stem or only malignant progenitor cells (average root mean square errors of 0.138 (13.8%) and 0.0874 (8.74%), respectively)., Discussion: Systematic simulation studies and fitting of the model to the patient data suggest that an initial reduction of the malignant cell burden followed by a monotonic increase can be recapitulated by the model assuming that ruxolitinib affects only the death rate of malignant progenitor cells. For patients exhibiting a long-term reduction of the malignant cells, the model predicts that ruxolitinib also affects stem cell parameters, such as the malignant stem cells' response to cytokine signalling., Competing Interests: The 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 © 2024 Boklund, Snyder, Gudmand-Hoeyer, Larsen, Knudsen, Eickhardt-Dalbøge, Skov, Kjær, Hasselbalch, Andersen, Ottesen and Stiehl.)

Background: International retirement migration, which is the seasonal or permanent relocation of older people to another country, has grown in popularity in recent years. These retirees are motivated by the promise of warmer winter climates that are conducive to participating in health-promoting recreational and social activities. Ease of cross-border travel facilitates this transnational practice when undertaken seasonally. However, border closures and other travel-related measures put in place to manage the spread of COVID-19, disrupted travel, including for older Canadians who typically winter in the United States (US). During the 2020-21 winter season, for example, Canadians were advised not to engage in non-essential international travel and the land border between Canada and the US was closed to all but essential travellers. Nonetheless, retirement migration remained a significant draw for many Canadian retirees. Here, we qualitatively explore the factors that Canadian international retirement migrants considered when deciding whether or not to travel to the US for the 2020-21 winter during the COVID-19 pandemic., Methods: Guided by case study methodology, semi-structured interviews were conducted with 31 Canadian international retirement migrants who had wintered in the US prior to the COVID-19 pandemic and were in the US at the outset of the pandemic in late winter 2020. Interviews were transcribed verbatim and thematically analyzed to decipher what factors were most important to their travel-related decision-making during the pandemic. We structure the thematic results around four factors previously identified to motivate older people to become international retirement migrants and thus inform decision-making: the destination, the people, the cost, and the movement., Results: The previously identified factors that motivate older people to participate in international retirement migration include: the destination (e.g., climate and amenities), the people (e.g., social networks), the cost (e.g., health insurance and living costs), and the movement (e.g., ease of travel). These factors informed how international retirement migrants made decisions to travel abroad or not in the 2020-21 winter season. For example, destination-based factors included a lack of public health measures and high case counts, people-based factors comprised of less opportunities to engage in social activities, cost-based factors involved maintaining property investments and the lack of COVID-19 treatment coverage in available travel health insurance plans, and movement-based factors included challenges in ease of access when travel was viewed as essential or non-essential. These factors disincentivized or motivated international retirement migrants to travel abroad in the 2020-21 winter season during the COVID-19 pandemic., Conclusions: The results of this study support the need to create tailored decision-support tools for international retirement migrants to make informed travel-related decisions during crisis events so as to protect their health and wellbeing. More research is needed to explore perceptions of risk, especially health risks, among international retirement migrants and how they differently affect their travel-related decisions., (© 2024. The Author(s).)

Purpose: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers., Methods: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions., Results: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions., Conclusion: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: In West Africa, healers greatly outnumber trained mental health professionals. People with serious mental illness (SMI) are often seen by healers in "prayer camps" where they may also experience human rights abuses. We developed "M&M," an 8-week-long dual-pronged intervention involving (1) a smartphone-delivered toolkit designed to expose healers to brief psychosocial interventions and encourage them to preserve human rights (M-Healer app), and (2) a visiting nurse who provides medications to their patients (Mobile Nurse)., Objective: We examined the feasibility, acceptability, safety, and preliminary effectiveness of the M&M intervention in real-world prayer camp settings., Methods: We conducted a single-arm field trial of M&M with people with SMI and healers at a prayer camp in Ghana. Healers were provided smartphones with M-Healer installed and were trained by practice facilitators to use the digital toolkit. In parallel, a study nurse visited their prayer camp to administer medications to their patients. Clinical assessors administered study measures to participants with SMI at pretreatment (baseline), midtreatment (4 weeks) and post treatment (8 weeks)., Results: Seventeen participants were enrolled and most (n=15, 88.3%) were retained. Participants had an average age of 44.3 (SD 13.9) years and 59% (n=10) of them were male. Fourteen (82%) participants had a diagnosis of schizophrenia and 2 (18%) were diagnosed with bipolar disorder. Four healers were trained to use M-Healer. On average, they self-initiated app use 31.9 (SD 28.9) times per week. Healers watched an average of 19.1 (SD 21.2) videos, responded to 1.5 (SD 2.4) prompts, and used the app for 5.3 (SD 2.7) days weekly. Pre-post analyses revealed a significant and clinically meaningful reduction in psychiatric symptom severity (Brief Psychiatric Rating Scale score range 52.3 to 30.9; Brief Symptom Inventory score range 76.4 to 27.9), psychological distress (Talbieh Brief Distress Inventory score range 37.7 to 16.9), shame (Other as Shamer Scale score range 41.9 to 28.5), and stigma (Brief Internalized Stigma of Mental Illness Scale score range 11.8 to 10.3). We recorded a significant reduction in days chained (1.6 to 0.5) and a promising trend for reduction in the days of forced fasting (2.6 to 0.0, P=.06). We did not identify significant pre-post changes in patient-reported working alliance with healers (Working Alliance Inventory), depressive symptom severity (Patient Health Questionnaire-9), quality of life (Lehman Quality of Life Interview for the Mentally Ill), beliefs about medication (Beliefs about Medications Questionnaire-General Harm subscale), or other human rights abuses. No major side effects, health and safety violations, or serious adverse events occurred over the course of the trial., Conclusions: The M&M intervention proved to be feasible, acceptable, safe, and clinically promising. Preliminary findings suggest that the M-Healer toolkit may have shifted healers' behaviors at the prayer camp so that they commit fewer human rights abuses., (© Dror Ben-Zeev, Anna Larsen, Dzifa A Attah, Kwadwo Obeng, Alexa Beaulieu, Seth M Asafo, Jonathan Kuma Gavi, Arya Kadakia, Emmanuel Quame Sottie, Sammy Ohene, Lola Kola, Kevin Hallgren, Jaime Snyder, Pamela Y Collins, Angela Ofori-Atta, M-Healer Research Team. Originally published in JMIR Mental Health (https://mental.jmir.org).)

Clinicopathological presentations are critical for establishing a postoperative treatment regimen in Colorectal Cancer (CRC), although the prognostic value is low in Stage 2 CRC. We implemented a novel exploratory algorithm based on artificial intelligence (explainable artificial intelligence, XAI) that integrates mutational and clinical features to identify genomic signatures by repurposing the FoundationOne Companion Diagnostic (F1CDx) assay. The training data set ( n = 378) consisted of subjects with recurrent and non-recurrent Stage 2 or 3 CRC retrieved from TCGA. Genomic signatures were built for identifying subgroups in Stage 2 and 3 CRC patients according to recurrence using genomic parameters and further associations with the clinical presentation. The summarization of the top-performing genomic signatures resulted in a 32-gene genomic signature that could predict tumor recurrence in CRC Stage 2 patients with high precision. The genomic signature was further validated using an independent dataset ( n = 149), resulting in high-precision prognosis (AUC: 0.952; PPV = 0.974; NPV = 0.923). We anticipate that our genomic signatures and NCCN guidelines will improve recurrence predictions in CRC molecular stratification.

Background: Few studies have evaluated mental health disorders comprehensively among patients with prostate cancer on long-term follow-up. The primary aim of our study was to assess the incidence of mental health disorders among patients with prostate cancer compared with a general population cohort. A secondary aim was to investigate potential risk factors for mental health disorders among patients with prostate cancer., Methods: Cohorts of 18 134 patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73470 men without cancer matched on age, birth state, and follow-up time were identified. Mental health diagnoses were identified from electronic health records and statewide health-care facilities data. Cox proportional hazard models were used to estimate hazard ratios. All statistical tests were 2-sided., Results: The hazard ratios for mood disorders, including depression, among prostate cancer survivors increased for all follow-up periods compared with the general population. The hazard ratios for any mental illness increased with Hispanic, Black, or multiple races; people who were underweight or obese; those with advanced prostate cancer; and those undergoing their first course cancer treatment. We also observed statistically significantly increased hazard ratios for mental health disorders among patients with lower socioeconomic status (P < .0001) and increasing duration of androgen-deprivation therapy (P = .0348). Prostate cancer survivors had a 61% increased hazard ratio for death with a depression diagnosis., Conclusion: Prostate cancer diagnosis was associated with a higher risk of mental health disorders compared with the general population, which was observed as long as 10-16 years after cancer diagnosis. Providing long-term mental health support may be beneficial to increasing life expectancy for patients with prostate cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract: As an ever-increasing number of physician assistant (PA) programs moves toward holistic admissions, a better understanding of how to achieve their stated admission goals becomes more important. With the June 2023 US Supreme Court decision effectively ending affirmative action in higher education, navigating holistic admissions is now an even greater challenge. In this article, the PA Education Association's Presidents Commission offers a guide for programs to use in implementing holistic admissions at their institutions and key considerations. Is the process mission-driven? Does it follow principles of quality improvement and incorporate ongoing assessment of that process? Using data can be a constructive and insightful way to inform the process. The authors hope that tools, resources, and recommendations offered in this article will serve as valuable resources for any program attempting to institute or improve its holistic admissions process., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2024 PA Education Association.)

Purpose: The program director (PD) is responsible for providing effective leadership and possessing knowledge of accreditation. The aim of this study was to evaluate whether a PD's experience in higher education affects the accreditation outcome., Methods: This cross-sectional study includes Physician Assistant (PA) programs that underwent an accreditation visit between January 2012 and January 2022. Data analysis was primarily descriptive, stratified by demographic variables, and outcomes of accreditation standards. Inferential analysis included chi-squared tests of statistical independence., Results: The chi-squared analysis test of statistical independence of PD's experience and accreditation decision identified a statistically significant association between the PD's experience as a PD and the accreditation outcome for continuing reviews. However, a minimum of 3 years of experience in higher education and the accreditation outcome were statistically independent for provisional and continuing reviews., Conclusion: Few PDs are hired with more than 3 years of PD experience, but they tend to have more higher education or PA program educational experience. A PD's years of higher education experience was not associated with accreditation outcome, which may suggest that other supports are more critical for achieving and maintaining accreditation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 PA Education Association.)

Purpose: This study simulates a novel prostate SBRT intra-fraction re-optimization workflow in MRIgART to account for prostate intra-fraction motion and evaluates the dosimetric benefit of reducing PTV margins., Materials and Methods: VMAT prostate SBRT treatment plans were created for 10 patients using two different PTV margins, one with a 5 mm margin except 3 mm posteriorly (standard) and another using uniform 2 mm margins (reduced). All plans were prescribed to 36.25 Gy in 5 fractions and adapted onto each daily MRI dataset. An intra-fraction adaptive workflow was simulated for the reduced margin group by synchronizing the radiation delivery with target position from cine MRI imaging. Intra-fraction delivered dose was reconstructed and prostate DVH metrics were evaluated under three conditions for the reduced margin plans: Without motion compensation (no-adapt), with a single adapt prior to treatment (ATP), and lastly for intra-fraction re-optimization during delivery (intra). Bladder and rectum DVH metrics were compared between the standard and reduced margin plans., Results: As expected, rectum V18 Gy was reduced by 4.4 ± 3.9%, D1cc was reduced by 12.2 ± 6.8% (3.4 ± 2.3 Gy), while bladder reductions were 7.8 ± 5.6% for V18 Gy, and 9.6 ± 7.3% (3.4 ± 2.5 Gy) for D1cc for the reduced margin reference plans compared to the standard PTV margin. For the intrafraction replanning approach, average intra-fraction optimization times were 40.0 ± 2.9 seconds, less than the time to deliver one of the four VMAT arcs (104.4 ± 9.3 seconds) used for treatment delivery. When accounting for intra-fraction motion, prostate V36.25 Gy was on average 96.5 ± 4.0%, 99.1 ± 1.3%, and 99.6 ± 0.4 for the non-adapt, ATP, and intra-adapt groups, respectively. The minimum dose received by the prostate was less than 95% of the prescription dose in 84%, 36%, and 10% of fractions, for the non-adapt, ATP, and intra-adapt groups, respectively., Conclusions: Intra-fraction re-optimization improves prostate coverage, specifically the minimum dose to the prostate, and enables PTV margin reduction and subsequent OAR sparing. Fast re-optimizations enable uninterrupted treatment delivery., Competing Interests: DH has received consulting fees, and travel support from Elekta AB for work not related to this study. JS and JSA have received Honoria and travel support from Eletka AB which is not related to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Snyder, Smith, Aubin, Shepard and Hyer.)

Background: Alternative cancer clinics, who provide treatment associated with earlier time to death, actively seek to create favorable views of their services online. An unexplored means where alternative cancer clinics can shape their appeal is their Google search results., Methods: We retrieved the Google listing and Google reviews of 47 prominent alternative cancer clinics on August 22, 2022. We then conducted a content analysis to assess the information cancer patients are faced with online., Results: Google listings of alternative treatment providers rarely declared the clinic was an alternative clinic versus a conventional primary cancer treatment provider (12.8% declared; 83.0% undeclared). The clinics were highly rated (median, 4.5 stars of 5). Reasons for positive reviews included treatment quality ( n  = 519), care ( n  = 420), and outcomes ( n  = 316). 288 reviews presented the clinics to cure or improve cancer. Negative reviews presented alternative clinics to financially exploit patients with ineffective treatment ( n  = 98), worsen patients' condition ( n  = 72), provide poor care ( n  = 41), and misrepresent outcomes ( n  = 23)., Conclusions: The favorable Google listing and reviews of alternative clinics contribute to harmful online ecosystems. Reviews provide compelling narratives but are an ineffective indicator of treatment outcomes. Google lacks safeguards for truthful reviews and should not be used for medical decision-making., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Introduction: To date, no international guidelines have been published for the treatment of paediatric functional abdominal pain disorders (FAPDs), subcategorised into functional abdominal pain-not otherwise specified (FAP-NOS), irritable bowel syndrome (IBS), functional dyspepsia and abdominal migraine (AM). We aim for a treatment guideline, focusing on FAP-NOS, IBS and AM, that appreciates the extensive array of available therapies in this field. We present the prospective operating procedure and technical summary protocol in this manuscript., Methods: Grading of Recommendations, Assessment, Development and Evaluation (GRADE) will be followed in the development of the guideline, following the approach as laid out in the GRADE handbook, supported by the WHO. The Guideline Development Group (GDG) is formed by paediatric gastroenterologists from both the European Society for Pediatric Gastroenterology, Hepatology and Nutrition, as well as the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Also, one clinical psychologist with expertise in FAPDs is a voting member in the GDG. A final consensus list of treatment options is translated into 'patient, intervention, comparison, outcome' format options. Prospective agreement on the magnitude of health benefits or harms categories was reached through a Delphi process among the GDG to support grading of the literature.There will be a detailed technical evidence review with randomised controlled trial data that will be judged for risk of bias with the Cochrane tool. Recommendations are preferably based on GRADE but could also be best practice statements following the available evidence. A full Delphi process will be used to make recommendations using online response systems. This set of procedures has been approved by all members of the GDG., 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.)

Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) is the most expensive and challenging insect pest of commercial pear trees in the Pacific Northwest. Integrated pest management (IPM) programs are working toward relying more heavily on natural enemies to reduce insecticide use. Trechnites insidiosus (Crawford) (Hymenoptera: Encyrtidae) is the main parasitoid of C. pyricola, but little is known about its biology in the region. Developing sampling tools is important for the deployment of IPM programs, including monitoring of natural enemies. In this study, we examined 2 conventional monitoring methods: beat trays and yellow sticky cards, in addition to screened sticky cards and 3D-printed cylinder traps. Additionally, we tested an overwintering trap for the collection of parasitized C. pyricola. The trapping methods were tested in orchards in Oregon and Washington. Unscreened cards caught the most T. insidiosus and C. pyricola, followed by screened cards, cylinder traps, and then beat trays. Beat trays sometimes failed to catch any T. insidiosus, even when it was found in abundance via other methods. Screened cards and cylinder traps reduced bycatch and increased ease of identifying T. insidiosus. Specimens from the cylinder traps were also more suitable for use in molecular analysis. The overwintering traps were effective at capturing parasitized C. pyricola, but were highly variable year to year. The ideal trapping method will vary based on research needs (e.g., DNA preservation, reducing bycatch, catching higher numbers), but both screened sticky cards and cylinder traps were viable methods for monitoring T. insidiosus and its host., (Published by Oxford University Press on behalf of Entomological Society of America 2023.)

Dengue is a global health issue, particularly in the tropical and subtropical regions of the world. Prevention is the most appropriate method to fight the spread of the virus. The objective of this research is to present a model, along with visualizations, that will enable health officials and community leaders to identify when and where potential dengue outbreaks are likely to occur. Armed with this information, local resources can be adequately deployed in an effort to use limited supplies effectively. A mathematical model that uses easily obtainable data, along with visualizations for the 80 barangays of Cebu City, Philippines, is presented. Visualizations are constructed appropriate for a generalist audience to comprehend and use for dengue mitigation. Results of this study include a model that uses readily available data to predict dengue outbreaks one month in advance and visualizations appropriate for decision-makers in public health. Additional items are identified that could enhance the explanatory power of the model, and future directions are discussed.

Background: Current methods of quantifying inflammation in chronic rhinosinusitis (CRS) on computed tomography (CT) imaging focus on opacification of the paranasal sinuses and show limited correlation with patient-reported outcome measures., Objective: This study aimed to determine if quantifying CT opacification of the nasal cavity correlated with Sino-Nasal Outcomes Test scores (SNOT-22)., Methods: Thirty patients with CRS were enrolled. Lund-Mackay and SNOT-22 scores were measured. Nasal cavity regions of interest (ROIs) were measured by 2 independent raters using ImageJ at 3 points on coronal CT scans: anteriorly at the lacrimal duct, at the approximate midpoint demarcated by the posterior aspect of the globe, and posteriorly at the transition from the hard to soft palate. Superior and inferior regions were defined based upon the root of the inferior turbinate. Percent opacification was calculated for each ROI. Analyses were conducted bilaterally and for the side with greater opacification (worse side)., Results: Interrater reliability was strong for all ROIs. Lund-Mackay scores correlated with nasal blockage only ( r  = .495, P  = .01) and did not correlate with nasal cavity ROI opacification. Inferior nasal cavity opacification for worse-sided anterior ROI and middle ROI correlated with SNOT-22 scores for nasal blockage (anterior r  = .41, P  = .03) (middle r  = .42, P  = .023) and runny nose (anterior r  = .44, P  = .02) (middle r  = .38, P  = .04). Posterior ROIs did not correlate with SNOT-22., Conclusions: Traditional CT scoring of sinus opacification does not correlate well with nasal cavity opacification or SNOT-22. Inferior nasal cavity inflammation provides unique correlations with SNOT-22 nasal questions and may guide targeted interventions in these regions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: No financial support was received. RJS is a consultant for OptiNose. The authors have no other relevant conflicts of interest or financial disclosures.

Background: Caregivers play a critical role in the treatment and recovery of youth and young adults at risk for psychosis. Caregivers often report feeling isolated, overwhelmed, and lacking in resources. Mobile health (mHealth) has the potential to provide scalable, accessible, and in-the-moment support to caregivers. To date, few if any mHealth resources have been developed specifically for this population., Objective: The aim of this study was to conduct user-centered design and testing of an mHealth intervention to support early psychosis caregivers., Methods: We conducted a multiphase user-centered development process to develop the Bolster mobile app. In phase 1, a total of 21 caregivers were recruited to participate in a qualitative needs assessment and respond to an initial prototype of the Bolster platform. Content analysis was used to identify key needs and design objectives, which guided the development of the Bolster mobile app. In phase 2, a total of 11 caregivers were recruited to participate in a 1-week field trial wherein they provided qualitative and quantitative feedback regarding the usability and acceptability of Bolster; in addition, they provided baseline and posttest assessments of the measures of distress, illness appraisals, and family communication., Results: In phase 1, participants identified psychoeducation, communication coaching, a guide to seeking services, and support for coping as areas to address. Live prototype interaction sessions led to multiple design objectives, including ensuring that messages from the platform were actionable and tailored to the caregiver experience, delivering messages in multiple modalities (eg, video and text), and eliminating a messaging-style interface. These conclusions were used to develop the final version of Bolster tested in the field trial. In phase 2, of the 11 caregivers, 10 (91%) reported that they would use Bolster if they had access to it and would recommend it to another caregiver. They also reported marked changes in their appraisals of illness (Cohen d=0.55-0.68), distress (Cohen d=1.77), and expressed emotion (Cohen d=0.52)., Conclusions: To our knowledge, this study is the first to design an mHealth intervention specifically for early psychosis caregivers. Preliminary data suggest that Bolster is usable, acceptable, and promising to improve key targets and outcomes. A future fully powered clinical trial will help determine whether mHealth can reduce caregiver burdens and increase engagement in services among individuals affected by psychosis., (©Benjamin Buck, Mary Wingerson, Erica Whiting, Jaime Snyder, Maria Monroe-DeVita, Dror Ben-Zeev. Originally published in JMIR Mental Health (https://mental.jmir.org), 30.11.2023.)

Purpose: Rural disparities in prostate cancer survivorship and cardiovascular disease remain. Prostate cancer treatment also contributes to worse cardiovascular disease outcomes. Our objective was to determine whether rural-urban differences in cardiovascular outcomes contribute to disparities in prostate cancer survivorship., Materials and Methods: Data were collected from the Utah Population Database. Rural and urban prostate cancer survivors were matched by diagnosis year and age. Cox proportional hazards models were used to estimate hazard ratios for cardiovascular disease (levels 1-3) based on rural-urban classification, while controlling for demographic and socioeconomic characteristics. We identified 3,379 rural and 16,253 urban prostate cancer survivors with a median follow-up of 9.3 years., Results: Results revealed that rural survivors had a lower risk of hypertension (HR 0.90), diseases of arteries (HR 0.92), and veins (HR 0.92) but a higher risk of congestive heart failure (HR 1.17). Interactions between level 2 cardiovascular diseases and rural/urban status, showed that diseases of the heart had a distinct between-group relationship for all-cause (P = 0.005) and cancer-specific mortality (P = 0.008)., Conclusions: This study revealed complex relationships between rural-urban status, cardiovascular disease, and prostate cancer. Rural survivors were less likely to be diagnosed with screen-detected cardiovascular disease but more likely to have heart failure. Further, the relationship between cardiovascular disease and survival was different between rural and urban survivors. It may be that our findings underscore differences in healthcare access where rural patients are less likely to be screened for preventable cardiovascular disease and have worse outcomes when they have a major cardiovascular event., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Rural cancer survivors experience considerable health disparities compared to urban cancer survivors for cancer treatment and survival. The objective of our study was to investigate the risk of developing diseases for rural compared to urban prostate cancer survivors in Utah., Methods: We identified a cohort of 3575 rural prostate cancer survivors and 17,778 urban prostate cancer survivors from the Utah Cancer Registry. The Fine-Gray subdistribution hazards model was used to estimate hazard ratios and 95 % confidence intervals for diseases in major body systems among rural compared to urban prostate cancer survivors at > 1-5 years and > 5 years after prostate cancer diagnosis., Results: Rural residence was associated with an increased risk of diseases of the respiratory system at > 5 years (HR: 1.16, 95 % CI: 1.01-1.32) after cancer diagnosis compared to urban residence among prostate cancer survivors in Utah. Decreased risks were observed in infectious and parasitic diseases, diseases of the blood and blood-forming organs, diseases of the nervous system and sense organs, and diseases of the skin and subcutaneous tissue for rural prostate cancer survivors between 1 and 5 years after cancer diagnosis., Conclusions: Rural prostate cancer survivors in Utah were somewhat healthier compared to urban prostate cancer survivors. Further studies are needed to confirm whether these associations are also supported for rural prostate cancer survivors in other regions of the U.S., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Detection and differentiation of brown fat in humans poses several challenges, as this tissue is sparse and often mixed with white adipose tissue. Non-invasive detection of beige fat represents an even greater challenge as this tissue is structurally and functionally more like white fat than brown fat. Here we used positron emission tomography with 18 F-fluorodeoxyglucose, computed tomography, xenon-enhanced computed tomography, and dynamic contrast-enhanced ultrasound, to non-invasively detect functional and structural changes associated with the browning process of inguinal white fat, induced in mice by chronic stimulation with the β 3 -adrenergic receptor agonist CL-316243. These studies reveal a very heterogeneous increase in baseline tissue radiodensity and xenon-enhanced radiodensity, indicative of both an increase in adipocytes water and protein content as well as tissue perfusion, mostly in regions that showed enhanced norepinephrine-stimulated perfusion before CL-316243 treatment. No statistically significant increase in 18 F-fluorodeoxyglucose uptake or norepinephrine-stimulated tissue perfusion were observed in the mice after the CL-316243 treatment. The increase in tissue-water content and perfusion, along with the negligible increase in the tissue glucose uptake and norepinephrine-stimulated perfusion deserve more attention, especially considering the potential metabolic role that this tissue may play in whole body metabolism., (© 2023. Springer Nature Limited.)

Purpose: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial., Methods and Materials: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ 2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject., Results: Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P = .04) and private versus public insurance (P < .001). Both patient (P = .008) and parent (P = .006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001)., Conclusions: In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: In 2021, 59.6% of low-risk patients with prostate cancer were under active surveillance (AS) as their first course of treatment. However, few studies have investigated AS and watchful waiting (WW) separately. The objectives of this study were to develop and validate a population-level machine learning model for distinguishing AS and WW in the conservative treatment group, and to investigate initial cancer management trends from 2004 to 2017 and the risk of chronic diseases among patients with prostate cancer with different treatment modalities., Methods: In a cohort of 18,134 patients with prostate adenocarcinoma diagnosed between 2004 and 2017, 1,926 patients with available AS/WW information were analyzed using machine learning algorithms with 10-fold cross-validation. Models were evaluated using performance metrics and Brier score. Cox proportional hazard models were used to estimate hazard ratios for chronic disease risk., Results: Logistic regression models achieved a test area under the receiver operating curve of 0.73, F -score of 0.79, accuracy of 0.71, and Brier score of 0.29, demonstrating good calibration, precision, and recall values. We noted a sharp increase in AS use between 2004 and 2016 among patients with low-risk prostate cancer and a moderate increase among intermediate-risk patients between 2008 and 2017. Compared with the AS group, radical treatment was associated with a lower risk of prostate cancer-specific mortality but higher risks of Alzheimer disease, anemia, glaucoma, hyperlipidemia, and hypertension., Conclusion: A machine learning approach accurately distinguished AS and WW groups in conservative treatment in this decision analytical model study. Our results provide insight into the necessity to separate AS and WW in population-based studies.

Purpose: The effect of obesity in penetrating trauma outcomes is poorly understood. The purpose of this study was to determine if there is a protective effect of subcutaneous or visceral fat from stab and gunshot wounds., Methods: 443 patients admitted after penetrating traumatic injury of the torso were retrospectively identified from our institution's trauma registry. CT scans performed at presentation were used to determine cross-sectional area of visceral and subcutaneous fat at the level of the umbilicus via manual segmentation. Obesity-associated parameters including body mass index, visceral and subcutaneous fat were compared with injury severity score, length of hospital/intesive care unit (ICU) stay, and number of operating room (OR) visits. Parameters were compared between patients who sustained stab wounds versus gunshot injuries., Results: Comparing all patients with gunshot injuries with those with stab injuries, gunshots resulted in increased hospital and ICU length of stay, and injury severity score (ISS). For patients with gunshot wounds, all obesity-related parameters correlated with increased length of stay and total ICU stay; subcutaneous fat and visceral fat were correlated with increased OR visits, but there was no significant correlation between obesity-related parameters and ISS. In contrast, with stab wounds there were no statistically significant associations between obesity parameters and any of the outcome measures., Conclusion: For penetrating trauma in the torso, obesity is correlated with worse outcomes with gunshot injuries but not in stab injuries., Level of Evidence: Level III, prognostic and epidemiological., 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.)

Purpose: The purpose of this work was to investigate the use of a segmentation approach that could potentially improve the speed and reproducibility of contouring during magnetic resonance-guided adaptive radiation therapy., Methods and Materials: The segmentation algorithm was based on a hybrid deep neural network and graph optimization approach that also allows rapid user intervention (Deep layered optimal graph image segmentation of multiple objects and surfaces [LOGISMOS] + just enough interaction [JEI]). A total of 115 magnetic resonance-data sets were used for training and quantitative assessment. Expert segmentations were used as the independent standard for the prostate, seminal vesicles, bladder, rectum, and femoral heads for all 115 data sets. In addition, 3 independent radiation oncologists contoured the prostate, seminal vesicles, and rectum for a subset of patients such that the interobserver variability could be quantified. Consensus contours were then generated from these independent contours using a simultaneous truth and performance level estimation approach, and the deviation of Deep LOGISMOS + JEI contours to the consensus contours was evaluated and compared with the interobserver variability., Results: The absolute accuracy of Deep LOGISMOS + JEI generated contours was evaluated using median absolute surface-to-surface distance which ranged from a minimum of 0.20 mm for the bladder to a maximum of 0.93 mm for the prostate compared with the independent standard across all data sets. The median relative surface-to-surface distance was less than 0.17 mm for all organs, indicating that the Deep LOGISMOS + JEI algorithm did not exhibit a systematic under- or oversegmentation. Interobserver variability testing yielded a mean absolute surface-to-surface distance of 0.93, 1.04, and 0.81 mm for the prostate, seminal vesicles, and rectum, respectively. In comparison, the deviation of Deep LOGISMOS + JEI from consensus simultaneous truth and performance level estimation contours was 0.57, 0.64, and 0.55 mm for the same organs. On average, the Deep LOGISMOS algorithm took less than 26 seconds for contour segmentation., Conclusions: Deep LOGISMOS + JEI segmentation efficiently generated clinically acceptable prostate and normal tissue contours, potentially limiting the need for time intensive manual contouring with each fraction., Competing Interests: Daniel E. Hyer reports a relationship with Elekta that includes consulting or advisory, funding grants, and speaking and lecture fees. Joseph Caster reports a relationship with Elekta that includes funding grants. Joel St-Aubin reports a relationship with Elekta that includes funding grants and speaking and lecture fees. Jeffrey Snyder reports a relationship with Elekta that includes funding grants and speaking and lecture fees. Honghai Zhang reports financial support was provided by the National Institute of Biomedical Imaging and Bioengineering. Sean Mullan reports financial support provided by National Heart Lung and Blood Institute. John Buatti reports a relationship with American Society for Radiation Oncology that includes board membership. Milan Sonka reports financial support from the National Institute of Biomedical Imaging and Bioengineering.

Introduction: Donation-based crowdfunding was heavily used during the COVID-19 pandemic. While most of these campaigns were uncontroversial, others spread misinformation or undermined public health. In response, mainstream crowdfunding platforms like GoFundMe restricted what campaigns they would host. This led some campaigns to shift to lesser-known and less restrictive crowdfunding platforms. While research on health-related misinformation on mainstream crowdfunding platforms is increasing, less is known about crowdfunding on less restrictive platforms like GiveSendGo. The aim of this study is to review vaccine-related crowdfunding campaigns on the GiveSendGo platform to better understand: 1) how vaccines are portrayed on GiveSendGo; and 2) how successful these campaigns have been at attracting financial support., Methods: We searched the GiveSendGo crowdfunding platform for campaigns including "vaccine" or "vaccination". This process yielded 907 unique results which were then scraped for their campaign text and fundraising data. The authors reviewed these campaigns for fundraisers whose aims related to vaccines for humans and assigned campaigns as being for 1) Accessing vaccines; 2) creating Spaces for the unvaccinated; 3) helping Unvaccinated Individuals); 4) Advocacy about vaccines; 5) supporting Anti-Mandate actions; and 6) responding to Vaccine Injuries., Findings: We identified 765 crowdfunding campaigns that raised $6,814,817 and requested $838,578,249. Anti-Mandate campaigns were most common, followed by Unvaccinated Individuals, Vaccine Injuries, Advocacy, Access, and Spaces. Only Access campaigns took a positive or neutral view toward vaccines. Themes of freedom and religion cut across campaign types with campaigns critical of vaccines invoking bodily autonomy and religious freedom as justifying their fundraisers., Discussion: Very few of these fundraisers met their goals. With the exception of Access campaigns, they frequently contained highly polarizing language advocating against public health mandates, misinformation about vaccine safety, and language from bioethics and reproductive choice advocates. Restrictions on vaccine-related campaigns on the GoFundMe platform likely drove campaign creation on GiveSendGo., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Snyder, Zenone. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Breast cancer is the most common non-skin cancer in women and an increasing number of people are living as breast cancer survivors. While the prognosis of breast cancer continues to improve, the rates of sexual dysfunction and the risk related to cancer treatments have not been well characterized in a population-based study., Methods: We identified a cohort of 19,709 breast cancer survivors diagnosed between 1997 and 2017 from the Utah Cancer Registry, and 93,389 cancer-free women who were matched by age and birth state from the Utah Population Database. Sexual dysfunction diagnoses were identified through ICD-9 and ICD-10 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios for risk of sexual dysfunction., Results: Breast cancer survivors were at higher risk of sexual dysfunction diagnosis (9.1% versus 6.9%, HR 1.60, 95% CI 1.51-1.70) compared to the general population. This risk increased 2.05-fold within 1 to 5 years after cancer diagnosis (95% CI 1.89-2.22) and 3.05-fold in individuals diagnosed with cancer at < 50 years of age (95% CI 2.65-3.51). Cancer treatments including endocrine therapy, chemotherapy and radiation therapy were associated with an increased risk of sexual dysfunction among breast cancer survivors., Conclusions: Risk of sexual dysfunction in breast cancer survivors is higher than in the general population, but may be underdiagnosed in the clinical setting. Health care professionals should be encouraged to address the topic of sexual health early on in the treatment of breast cancer, and routinely screen patients for symptoms of sexual dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The purpose of this trial was to assess the patient and physician-reported toxicity in anal cancer patients undergoing definitive chemoradiation with intensity-modulated proton therapy (IMPT)., Methods: Patients with stage II and III anal cancer were treated with IMPT. All patients received 2 cycles of 5-fluorouracil and mitomycin concurrently with radiation. Toxicity was assessed at baseline, weekly during chemoradiation, and in follow-up using physician-graded common terminology criteria for adverse events (CTCAE) v 4.0 and PRO-CTCAE. The primary endpoint was to define point estimates and 95% CI for acute ≥ grade 2/3 gastrointestinal (GI), genitourinary (GU), dermatologic, and hematologic toxicity. The proportion of PRO-CTCAE questions scored ≥3 for each domain was compared with the baselinse. The proportion of ≥ grade 2 and ≥ grade 3 toxicities were compared with historic intensity-modulated radiotherapy patients treated on RTOG 0529., Results: Fourteen patients were enrolled from 2017 to 2020. Rates of physician-reported GI, GU, dermatologic, and hematologic toxicity were not significantly different between patients treated with IMPT compared with patients treated with intensity-modulated radiotherapy. Rates of patient-reported dermatologic and GU toxicity were low at baseline with a peak at week 6 (91% and 58% PRO-CTCAE items ≥ grade 3, respectively) and normalization to baseline 3 months after IMPT. In contrast, the proportion of high-grade PRO-CTCAE GI scores was 40% at baseline, which persisted through 1-year posttreatment., Conclusions: Clinician-reported toxicity was not improved with IMPT in the context of this underpowered trial. High-grade GI symptoms persisted for 12 months and were similar to baseline. Additional measures are needed to minimize acute and chronic toxicity related to chemoradiation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)