Sociodemographic and geographic factors impacting radiotherapy recommendation, initiation, and completion for patients with cancer.

BACKGROUND: More than half of patients with cancer receive radiotherapy, which often requires daily treatments for several weeks. The impact of geographic and sociodemographic factors on the odds of patients with cancer being recommended radiotherapy, starting radiotherapy, and completing radiotherapy is not well understood. METHODS: This was a retrospective patient cohort study that included patients diagnosed with one of the 10 most common solid cancers from January 1, 2018, to December 31, 2021, in the National Cancer Database. The primary predictor was radial distance from a patient's home to their cancer treatment hospital. Other covariates included baseline patient characteristics (age, sex, comorbidities, metastatic disease, cancer site), sociodemographic characteristics (race, ethnicity, median income quartile, insurance status), geographic region, and facility type. The three primary outcomes were being recommended radiotherapy, starting recommended radiotherapy, and completing radiotherapy. RESULTS: Of the 3,068,919 patients included, patients living >50 miles away had lower odds of being recommended radiotherapy than those living <10 miles away. Compared to White patients, Asian and Hispanic patients had lower odds of being recommended radiotherapy, and Black patients had lower odds of starting recommended radiotherapy. Uninsured patients, those with Medicaid or Medicare, and patients in lower median income quartiles had lower odds of starting or completing radiotherapy. CONCLUSIONS: Geographic and sociodemographic factors impact access to radiotherapy at different levels in cancer care and understanding these factors could aid policymakers and practices in identifying and supporting at-risk patients.

Breast implant illness: A United Kingdom patient-centred approach.

INTRODUCTION: Silicone breast implants are widely prevalent. An increasing group of patients detail self-reported somatic and psychological symptoms that have been ascribed as breast implant illness (BII) and seek capsulectomy and implant removal. To guide consultations and shared decision making, more outcome data relating to this intervention are required. AIM: To present a multicentre study of patient-centred (n = 100) outcome data, following total capsulectomy with implant removal for BII. METHOD: A questionnaire survey was cross-referenced with medical records. Collected data included demographics, operation details, pre- and postoperative symptom scores, overall self-perceived percentage improvement in BII symptoms and breast shape satisfaction ratings after explantation. RESULTS: The 10 most frequently self-reported symptoms were fatigue (81%), pains/aches (72%), brain/memory fog (56%), mood disturbances (36%), neuropathic pain (28%), hair loss (28%), headaches (25%), gastric symptoms/intolerances (24%), eczema/rash (18%) and vision disturbance (17%). A high proportion of patients (98%) experienced a 62 ±â€¯4% average symptom improvement; most self-reported symptoms (21/28) improved significantly after explantation with total capsulectomy (p < 0.05). Furthermore, patients had high overall self-perceived BII percentage improvement (76 ±â€¯3%) and satisfaction with breast shape numerical rating score (8 ±â€¯0.30) postoperatively. CONCLUSION: Despite BII not being a defined disease entity, symptom association with silicone breast implants continues for a growing number of patients. It is important to recognise that in this patient group, capsulectomy and implant removal may not be curative, however we have demonstrated that symptom improvement can occur. It is very difficult to prove a causal link between breast implants and BII; to do so will require extensive prospective data collection.

Multimodal optical imaging of the oculofacial region using a solid tissue-simulating facial phantom.

Significance: Spatial frequency domain imaging (SFDI) applies patterned near-infrared illumination to quantify the optical properties of subsurface tissue. The periocular region is unique due to its complex ocular adnexal anatomy. Although SFDI has been successfully applied to relatively flat in vivo tissues, regions that have significant height variations and curvature may result in optical property inaccuracies. Aim: We characterize the geometric impact of the periocular region on SFDI imaging reliability. Approach: SFDI was employed to measure the reduced scattering coefficient ( µ s ' ) and absorption coefficient ( µ a ) of the periocular region in a cast facial tissue-simulating phantom by capturing images along regions of interest (ROIs): inferior temporal quadrant (ITQ), inferior nasal quadrant (INQ), superior temporal quadrant (STQ), central eyelid margin (CEM), rostral lateral nasal bridge (RLNB), and forehead (FH). The phantom was placed on a chin rest and imaged nine times from an "en face" or "side profile" position, and the flat back of the phantom was measured 15 times. Results: The measured µ a and µ s ' of a cast facial phantom are accurate when comparing the ITQ, INQ, STQ, and FH to its flat posterior surface. Paired t tests of ITQ, INQ, STQ, and FH µ a and µ s ' concluded that there is not enough evidence to suggest that imaging orientation impacted the measurement accuracy. Regions of extreme topographical variation, i.e., CEM and RLNB, did exhibit differences in measured optical properties. Conclusions: We are the first to evaluate the geometric implications of wide-field imaging along the periocular region using a solid tissue-simulating facial phantom. Results suggest that the ITQ, INQ, STQ, and FH of a generalized face have minimal impact on the SFDI measurement accuracy. Areas with heightened topographic variation exhibit measurement variability. Device and facial positioning do not appear to bias measurements. These findings confirm the need to carefully select ROIs when measuring optical properties along the periocular region.

Nanocarrier design for pathogen-inspired innate immune agonist delivery.

In complex diseases such as cancer, modulating cytokine signatures of disease using innate immune agonists holds therapeutic promise. Novel multi-agonist treatments offer tunable control of the immune system because they are uniquely pathogen inspired, eliciting robust antitumor responses by promoting synergistic cytokine responses. However, the chief strategic hurdle is ensuring multi-agonist delivery to the same target cells, highlighting the importance of using nanomaterial-based carriers. Here, we place nanocarriers in center stage and review the delivery hurdles related to the varying extra- and intracellular localizations of innate immune receptors. We discuss a range of nanomaterials used for multi-agonist delivery, highlighting their respective benefits and drawbacks. Our overarching stance is that rational nanocarrier design is crucial for developing pathogen-inspired multi-agonist immunotherapies.

Risk of corrected QT interval prolongation in patients receiving antipsychotics.

Antipsychotic (AP) use has been associated to QT interval prolongation on the surface electrocardiogram (ECG). Our study aimed to determine the incidence of corrected QT (QTc) interval prolongation among patients admitted to a psychiatric hospitalization unit requiring AP treatment and to assess the relationship between administered dose and QTc interval changes. We enrolled 179 patients admitted to the Hospital Psiquiátrico Departamental Universitario del Valle in Cali, Colombia. ECGs were conducted upon admission, and again at 3 and 7 days postadmission. The QT interval was measured, and QTc interval correction was performed using Bazzet's formula. QTc interval prolongation at time points B or C was observed in 9.5% of patients. Clozapine was the most common AP associated with QTc interval prolongation (20.59%), followed by olanzapine (15.38%). The relative risk of QT interval prolongation with clozapine compared to haloperidol was 4.17 (95% confidence interval, 1.14-15.17, P = 0.02). AP use upon hospital admission was linked to early (within 3 days) QTc interval prolongation. Clozapine and olanzapine were associated with a greater increase in QTc interval compared to haloperidol, indicating a need for rigorous electrocardiographic monitoring with their use.

Genomic SNPs resolve the phylogeny of an ancient amphibian island radiation from the Seychelles.

Unusually for oceanic islands, the granitic Seychelles host multiple lineages of endemic amphibians. This includes an ancient (likely ca. 60 million years) radiation of eight caecilian species, most of which occur on multiple islands.These caecilians have a complicated taxonomic history and their phylogenetic inter-species relationships have been difficult to resolve. Double-digest RAD sequencing (ddRADseq) has been applied extensively to phylogeography and increasingly to phylogenetics but its utility for resolving ancient divergences is less well established. To address this, we applied ddRADseq to generate a genome-wide SNP panel for phylogenomic analyses of the Seychelles caecilians, whose phylogeny has so far not been satisfactorily resolved with traditional DNA markers. Based on 129,154 SNPs, we resolved deep and shallow splits, with strong support. Our findings demonstrate the capability of genome-wide SNPs for evolutionary inference at multiple taxonomic levels and support the recently proposed synonymy of Grandisonia Taylor, 1968 with Hypogeophis Peters, 1879. We revealed three clades of Hypogeophis (large-, medium- and short-bodied) and identify a single origin of the diminutive, stocky-bodied and pointy-snouted phenotype.

Microbiota and metabolic adaptation shape Staphylococcus aureus virulence and antimicrobial resistance during intestinal colonization.

Depletion of microbiota increases susceptibility to gastrointestinal colonization and subsequent infection by opportunistic pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). How the absence of gut microbiota impacts the evolution of MRSA is unknown. The present report used germ-free mice to investigate the evolutionary dynamics of MRSA in the absence of gut microbiota. Through genomic analyses and competition assays, we found that MRSA adapts to the microbiota-free gut through sequential genetic mutations and structural changes that enhance fitness. Initially, these adaptations increase carbohydrate transport; subsequently, evolutionary pathways largely diverge to enhance either arginine metabolism or cell wall biosynthesis. Increased fitness in arginine pathway mutants depended on arginine catabolic genes, especially nos and arcC, which promote microaerobic respiration and ATP generation, respectively. Thus, arginine adaptation likely improves redox balance and energy production in the oxygen-limited gut environment. Findings were supported by human gut metagenomic analyses, which suggest the influence of arginine metabolism on colonization. Surprisingly, these adaptive genetic changes often reduced MRSA's antimicrobial resistance and virulence. Furthermore, resistance mutation, typically associated with decreased virulence, also reduced colonization fitness, indicating evolutionary trade-offs among these traits. The presence of normal microbiota inhibited these adaptations, preserving MRSA's wild-type characteristics that effectively balance virulence, resistance, and colonization fitness. The results highlight the protective role of gut microbiota in preserving a balance of key MRSA traits for long-term ecological success in commensal populations, underscoring the potential consequences on MRSA's survival and fitness during and after host hospitalization and antimicrobial treatment.

Refining Parent SMART: User feedback to optimize a multi-modal intervention.

INTRODUCTION: The continuing care period following residential substance use treatment is a time when adolescents are at especially high risk for relapse, yet few families engage in traditional office-based care. Parent SMART (Substance Misuse among Adolescents in Residential Treatment) is a multi-component continuing care intervention for parents that combines three digital health technologies - an "off the shelf" online parenting program, daily phone notifications, and an online parent networking forum - with support from a parent coach. The current study solicited both qualitative and quantitative user feedback about Parent SMART to ensure responsivity to user preferences, refinement, and continuous improvement of the intervention. METHODS: Exit interviews were conducted with 30 parents who received Parent SMART, which includes (1) a parent networking forum; (2) daily text messages reminders of skills, (3) an "off-the-shelf" online parenting program; and (4) in-person or telehealth parent coaching sessions. The study collected qualitative feedback using semi-structured interviews and obtained quantitative feedback via a series of ratings of each Parent SMART component on a 5-point Likert scale administered at each follow-up assessment. RESULTS: Quantitative feedback suggest that parents rated all four elements of Parent SMART as easy to use. Qualitative feedback revealed that parents valued several aspects of Parent SMART including the brevity and structure of the intervention elements, the reminders to use parenting skills, and the sense of social connectedness fostered by different components. Recommended refinements included a number of strategies to enhance personalization and ease of navigation. CONCLUSIONS: Parent feedback informed enhancements to the Parent SMART intervention prior to implementation in a larger, ongoing pragmatic effectiveness trial. The current study serves as a model for applying a staged person-centered approach and eliciting both quantitative and qualitative feedback to refine digital health technologies.

Practice Consolidation Among US Medical Oncologists, 2015-2022.

PURPOSE: Health care consolidation has significantly affected cancer care delivery, with oncology practices undergoing substantial consolidation over the past two decades. This study investigates practice consolidation trends among medical oncologists (MOs), factors associated with consolidation, and changes in MO geographic distribution. METHODS: Medicare data from 2015 to 2022 were used to assess MO practice consolidation in hospital referral regions (HRRs), linked with regional health care market data and physician demographics. The Herfindahl-Hirschman Index (HHI) was used to measure consolidation, and the Gini coefficient was used to measure MO distribution across counties. Multivariable linear regression explored factors associated with MO practice consolidation. RESULTS: Between 2015 and 2022, the number of MOs increased by 14.5% (11,727-13,433), whereas the number of MO practices decreased by 18.0% (2,774-2,276). The mean number of MOs per practice increased by 40% (4.26-5.95; P < .001). The percentage of MOs in small practices decreased, whereas larger practices saw an increase. MO consolidation, as indicated by the HHI, increased by 9% (median HHI, 0.3204-0.3480). HRRs with higher baseline hospital consolidation and more hospital beds per capita were more likely to have MO practice consolidation. Despite MO practice consolidation, the county-level distribution of MOs did not change substantially. CONCLUSION: On the basis of Federal Trade Commission classifications, MO practices were highly concentrated in 2015 and consolidated even further by 2022. While distribution of MOs at the county level remained stable, further research is needed to assess the effects of rapid consolidation on cancer care cost, quality, and access. These data have important implications for policymakers and payers as they design programs that ensure high-quality, affordable cancer care.

Accreditation Standards-An Untapped Lever for Cancer Equity.

This Viewpoint describes how the Commission on Cancer and the National Cancer Institute can incorporate health equity benchmarks into existing standards to improve care and outcomes for all patients with cancer.

Prefrontal Regulation of Safety Learning during Ethologically Relevant Thermal Threat.

Learning and adaptation during sources of threat and safety are critical mechanisms for survival. The prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) have been broadly implicated in the processing of threat and safety. However, how these regions regulate threat and safety during naturalistic conditions involving thermal challenge still remains elusive. To examine this issue, we developed a novel paradigm in which adult mice learned that a particular zone that was identified with visuospatial cues was associated with either a noxious cold temperature ("threat zone") or a pleasant warm temperature ("safety zone"). This led to the rapid development of avoidance behavior when the zone was paired with cold threat or approach behavior when the zone was paired with warm safety. During a long-term test without further thermal reinforcement, mice continued to exhibit robust avoidance or approach to the zone of interest, indicating that enduring spatial-based memories were formed to represent the thermal threat and thermal safety zones. Optogenetic experiments revealed that neural activity in PL and IL was not essential for establishing the memory for the threat zone. However, PL and IL activity bidirectionally regulated memory formation for the safety zone. While IL activity promoted safety memory during normal conditions, PL activity suppressed safety memory especially after a stress pretreatment. Therefore, a working model is proposed in which balanced activity between PL and IL is favorable for safety memory formation, whereas unbalanced activity between these brain regions is detrimental for safety memory after stress.

Trends in Utilization and Medicare Spending on Short-Course Radiation Therapy for Breast and Prostate Cancer: An Episode-Based Analysis From 2015 to 2019.

PURPOSE: Evidence supports the value of shorter, similarly efficacious, and potentially more cost-effective hypofractionated radiation therapy (RT) regimens in many clinical scenarios for breast cancer (BC) and prostate cancer (PC). However, practice patterns vary considerably. We used the most recent Centers for Medicare and Medicaid Services data to assess trends in RT cost and practice patterns among episodes of BC and PC. METHODS AND MATERIALS: We performed a retrospective cohort analysis of all external beam RT episodes for BC and PC from 2015 to 2019 to assess predictors of short-course RT (SCRT) use and calculated spending differences. Multivariable logistic regression defined adjusted odds ratios of receipt of SCRT over longer-course RT (LCRT) by treatment modality, age, year of diagnosis, type of practice, and the interaction between year and treatment setting. Medicare spending was evaluated using multivariable linear regression controlling for duration of RT regimen (SCRT vs LCRT) in addition to the above covariables. RESULTS: Of 143,729 BC episodes and 114,214 PC episodes, 63,623 (44.27%) and 25,955 (22.72%) were SCRT regimens, respectively. Median total spending for SCRT regimens among BC episodes was $9418 (interquartile range [IQR], $7966-$10,983) versus $13,602 (IQR, $11,814-$15,499) for LCRT. Among PC episodes, median total spending was $6924 (IQR, $4,509-$12,905) for stereotactic body RT, $18,768 (IQR, $15,421-$20,740) for moderate hypofractionation, and $27,319 (IQR, $25,446-$29,421) for LCRT. On logistic regression, receipt of SCRT was associated with older age among both BC and PC episodes as well as treatment at hospital-affiliated over freestanding sites (P < .001 for all). CONCLUSIONS: In this evaluation of BC and PC RT episodes from 2015 to 2019, we found that shorter-course RT resulted in lower costs than longer-course RT. SCRT was also more common in hospital-affiliated sites. Future research focusing on potential payment incentives encouraging SCRT when clinically appropriate in the 2 most common cancers treated with RT will be valuable as the field continues to prospectively evaluate cost-effective hypofractionation in other disease sites.

Pragmatic Implementation of a Music Intervention in Nursing Homes Before and During COVID-19.

OBJECTIVES: We conducted 2 trials of a music intervention for managing behaviors in nursing home (NH) residents with dementia, before (2019) and during (2021) the pandemic. In this report, we compare adherence fidelity across the trials using the Framework for Implementation Fidelity (FIF). DESIGN: Cross-sectional, descriptive implementation comparison. SETTING AND PARTICIPANTS: Fifty-four NHs randomized to receive the intervention (27 pre-COVID, 27 during COVID) METHODS: We compare the trials on the following FIF criteria: coverage (number of residents receiving the intervention); duration (minutes of music received per exposed day); frequency (percentage of residents with nursing staff use of music in the past week); and details of content (adherence to core components of the intervention). We report NH-level performance in each domain and compare characteristics of NHs in the bottom (low) and top (high) terciles of adherence. RESULTS: Across FIF domains, adherence fidelity was lower during COVID compared with pre-COVID: coverage, residents exposed (COVID: 7.5, SD 5.6; pre-COVID: 12.7, SD 3.6); duration, music minutes per exposed day (COVID: 2.5, SD 5.1; pre-COVID: 27.1, SD 23.9); frequency, percentage of residents with nursing use of intervention in the past week (COVID: 15.0, SD 31.5; pre-COVID 40.4, SD 25.6); and details of content, compliance with core components of the intervention (COVID: 8.3, SD 1.9; pre-COVID 9.6, SD 2.0). In both trials, high-adherence fidelity NHs had better nursing staff ratios, greater percentages of Medicare residents, and lower percentages of Black residents, compared with low-fidelity NHs. CONCLUSIONS AND IMPLICATIONS: Adherence fidelity was worse in the COVID vs pre-COVID trial, despite adaptations between trials intended to reduce staff burden and increase clinical targeting of the intervention. Results may point to the long-term effects of COVID on quality improvement capacity in NHs and/or a lack of available resources in most NHs to implement complex behavioral interventions without direct research support.

Incidence and Reimbursement Trends for Facial Fracture Repair in the Elderly: A Medicare Analysis.

OBJECTIVES: The aim was to describe incidence and reimbursement trends of surgical repair of facial fractures among the Medicare population. METHODS: The annual procedure data from the Centers for Medicare and Medicaid Service National Part B Data File from 2000 to 2019 were queried. RESULTS: The total number of surgically corrected facial fractures increased from 10,148 in 2000 to 19,631 in 2019 in a linear pattern (r = 0.924). Specifically, nasal bone/septum fracture repairs increased the most by 200.6% (n = 4682 to n = 14,075), whereas operations for TMJ dislocations, malar/zygoma fractures, and alveolar ridge/mandibular fractures decreased by 27.9%, 12.3%, and 3.2%, respectively, between 2000 and 2019. Correspondingly, the total Medicare reimbursement rose from $2,574,317 in 2000 to $4,129,448 in 2019 (r = 0.895). However, the mean reimbursement for all procedures decreased from $376.63 to $210.35 (44.1% fall) over the same time after adjusting for inflation, with this trend holding for individual fracture types as well. CONCLUSIONS: Given the population's increasing age, there has been a significant increase in the number of surgical repairs of facial fractures in Medicare patients between 2000 and 2019. However, this is largely driven by an increase in nasal bone/septum closed reductions, with stagnant and, in some cases, declining incidence among other fracture repairs. The reason is unclear and may be related to an increase in nonoperative management or poor outcomes. Nevertheless, like other subfields within otolaryngology and medicine at large, payments have lagged far behind, which may play some role. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:659-665, 2024.

La historia olvidada del alzhéimer: recordando a Oskar Fischer

Introducción: La Enfermedad de Alzheimer (EA), es una patología neurodegenerativa progresiva que afecta la memoria y otras funciones cognitivas. Hasta ahora no existen tratamientos curativos ni modificadores de la enfermedad, por lo que el manejo está centrado en la prevención y en el tratamiento de factores que puedan contribuir a su evolución; las herramientas farmacológicas son escasas y tienen efectos modestos en la ralentización de la enfermedad. Se propone realizar una breve biografía de Oskar Fischer, describir el conflicto con Alois Alzheimer que se identifica en documentos científicos y mencionar los principales elementos de la teoría de Oskar Fischer. Método: Se realizó una revisión narrativa en las bases de datos Scielo, PubMed y Lilacs, con los términos "Oskar Fischer" y se encontró quince artículos publicados entre 1906 a 2023, los cuales fueron resumidos por los autores GS y NR. El artículo fue posteriormente revisado por los demás autores. Resultados: Se organizaron en secciones, partiendo con una breve biografía del autor, su interacción con Alois Alzheimer y un resumen de su teoría; lo descrito por Oskar Fischer en términos de las estructuras de placas y ovillos se considera como una de las principales teorías fisiopatológicas de la EA. Conclusiones: Oskar Fisher hizo un aporte invaluable y planteó conceptos clásicos con respecto a la EA, que, si bien no le valieron para ser reconocido en la posteridad, han permitido que en las investigaciones posteriores sea de gran importancia repensar estos conceptos e incluir otras posibilidades e hipótesis, para continuar en la profundización del conocimiento de la enfermedad.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative pathology that affects memory and other cognitive functions. Until now, there are no curative or disease-modifying treatments, so management is focused on prevention and treatment of factors that may contribute to its evolution; pharmacological tools are scarce and have modest effects in slowing the disease. It is proposed to make a brief biography of Oskar Fischer, describe the conflict with Alois Alzheimer that is identified in scientific documents and mention the main elements of Oskar Fischer's theory. Method: A narrative review was carried out in the Scielo, PubMed and Lilacs databases, with the terms "Oskar Fischer" and fifteen articles published between 1906 and 2023 were found, which were summarized by the authors GS and NR. The article was subsequently reviewed by the other authors. Results: They were organized in sections, starting with a brief biography of the author, his interaction with Alois Alzheimer and a summary of his theory; what was described by Oskar Fischer in terms of the structures of plaques and tangles is considered one of the main pathophysiological theories of AD. Conclusions: Oskar Fisher made an invaluable contribution and raised classic concepts regarding AD, which, although they did not earn him recognition in posterity, have allowed subsequent research to be of great importance to rethink these concepts and include other possibilities and hypotheses, to continue deepening the knowledge of the disease.