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OBJECTIVE: This study aimed to understand reasons for interobserver variability in the grading of oral epithelial dysplasia (OED) through a survey of pathologists to provide insight for improvements in the reliability and reproducibility of OED diagnoses. METHODS: The study design included quantitative and qualitative methodology. A pre-validated 31-item questionnaire was distributed to general, head and neck, and oral and maxillofacial histopathology specialists worldwide. RESULTS: A total of 132 pathologists participated and completed the questionnaire. Over two-thirds used the three-tier grading system for OED, while about a third used both binary and three-tier systems. Regular reporters of OED preferred the three-tier system and grading architectural features. Continuing education significantly aided recognition of architectural and cytological changes. Irregular epithelial stratification and drop-shaped rete ridges had the lowest prognostic value and recognition scores, while loss of epithelial cell cohesion had the highest. Most participants used clinical information and often sought a second opinion when grading OED. CONCLUSION: Our study has found that frequency of OED reporting and attendance of CME/CPD can play an important role in grading OED. Variations in the prognostic value of individual histological features and the use of clinical information may further contribute to interobserver variability.
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During spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during 'offline' resting periods, brief neuronal population bursts can 'replay' sequences of activity that resemble bouts of sensory experience. These sequences can occur in either forward or reverse order, and can even include spatial trajectories that have not been experienced, but are consistent with the topology of the environment. The neural circuit mechanisms underlying this variable and flexible sequence generation are unknown. Here we demonstrate in a recurrent spiking network model of hippocampal area CA3 that experimental constraints on network dynamics such as population sparsity, stimulus selectivity, rhythmicity and spike rate adaptation, as well as associative synaptic connectivity, enable additional emergent properties, including variable offline memory replay. In an online stimulus-driven state, we observed the emergence of neuronal sequences that swept from representations of past to future stimuli on the timescale of the theta rhythm. In an offline state driven only by noise, the network generated both forward and reverse neuronal sequences, and recapitulated the experimental observation that offline memory replay events tend to include salient locations like the site of a reward. These results demonstrate that biological constraints on the dynamics of recurrent neural circuits are sufficient to enable memories of sensory events stored in the strengths of synaptic connections to be flexibly read out during rest and sleep, which is thought to be important for memory consolidation and planning of future behaviour. KEY POINTS: A recurrent spiking network model of hippocampal area CA3 was optimized to recapitulate experimentally observed network dynamics during simulated spatial exploration. During simulated offline rest, the network exhibited the emergent property of generating flexible forward, reverse and mixed direction memory replay events. Network perturbations and analysis of model diversity and degeneracy identified associative synaptic connectivity and key features of network dynamics as important for offline sequence generation. Network simulations demonstrate that population over-representation of salient positions like the site of reward results in biased memory replay.
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Hipocampo , Neuronas , Neuronas/fisiología , Hipocampo/fisiología , Ritmo Teta/fisiología , Sueño/fisiologíaRESUMEN
Construct: The construct being assessed is readiness-for-residency of graduating medical students, as measured through two assessment frameworks. Background: Readiness-for-residency of near-graduate medical students should be but is not consistently assessed. To address this, the Association of American Medical Colleges (AAMC), in 2014, identified and described 13 core Entrustable Professional Activities (EPAs), which are tasks that all residents should be able to perform unsupervised upon entering residency. However, the AAMC did not initially provide measurement guidelines or propose standardized assessments. We designed Night-onCall (NOC), an immersive simulation for our near-graduating medical students to assess and address their readiness-for-residency, framed around tasks suggested by the AAMC's core EPAs. In adopting this EPA assessment framework, we began by building upon an established program of competency-based clinical skills assessments, repurposing competency-based checklists to measure components of the EPAs where possible, and designing new checklists, when necessary. This resulted in a blended suite of 14 checklists, which theoretically provide substantive assessment of all 13 core EPAs. In this paper, we describe the consensus-based mapping process conducted to ensure we understood the relationship between competency and EPA-based assessment lenses and could therefore report meaningful feedback on both to transitioning students in the NOC exercise. Approach: Between January-November 2017, five clinician and two non-clinician health professions educators at NYU Grossman School of Medicine conducted a rigorous consensus-based mapping process, which included each rater mapping each of the 310 NOC competency-based checklist items to lists of entrustable behaviors expected of learners according to the AAMC 13 core EPAs. Findings: All EPAs were captured to varying degrees by the 14 NOC checklists (overall Intraclass Correlation Coefficient (ICC) = 0.77). Consensus meetings resolved discrepancies and improved ICC values for three (EPA-9, EPA-10, EPA-12) of the four EPAs that initially showed poor reliability. Conclusions: Findings suggest that with some limitations (e.g., EPA-7 "form clinical questions/retrieve evidence") established competency-based assessments can be repurposed to measure readiness-for-residency through an EPA lens and both can be reported to learners and faculty.
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BACKGROUND: Acute alcohol consumption and chronic alcohol consumption increase the burden placed on emergency departments (EDs) by contributing to injury and disease. Whether the prevalence of alcohol-related ED visits in the United States has changed in recent years is unknown. The purpose of this study was to examine trends in ED visits involving acute and chronic alcohol consumption in the United States by age and sex between 2006 and 2014. METHODS: Data from the Nationwide Emergency Department Sample (NEDS), the largest all-payer ED database in the United States involving 945 hospitals in 33 states and Washington, DC, were analyzed to assess changes in prevalence and rates of ED visits involving acute and chronic alcohol consumption by age and sex over time among persons aged ≥12 between 2006 and 2014. RESULTS: Between 2006 and 2014, the number of ED visits involving alcohol consumption increased 61.6%, from 3,080,214 to 4,976,136. The rate increased 47% from 1,223 to 1,802 per 100,000 population and the total cost of such visits increased 272% from $4.1 billion to $15.3 billion. The number of acute alcohol-related ED visits increased 51.5% from 1,801,006 to 2,728,313 and the rate increased 40% from 720.9 to 1,009.6 per 100,000 population. The number chronic alcohol-related visits increased 75.7% from 1,279,208 to 2,247,823 and the rate increased 57.9% from 502.2 to 792.9 per 100,000. The annual percentage change in rates of all alcohol-related ED visits was larger for females than for males (5.3% vs. 4.0%). Other drug involvement increased the likelihood of admission for inpatient treatment. CONCLUSIONS: Alcohol consumption contributed to an increasing number of ED visits in the United States between 2006 and 2014, especially among females. Increased utilization of evidence-based interventions is needed.
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Trastornos Relacionados con Alcohol/epidemiología , Intoxicación Alcohólica/epidemiología , Servicio de Urgencia en Hospital/tendencias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Bases de Datos Factuales , Servicio de Urgencia en Hospital/economía , Femenino , Costos de la Atención en Salud , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por Sexo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Acquired aplastic anemia is an autoimmune-mediated bone marrow failure syndrome. The mechanism by which such an autoimmune reaction is initiated is unknown. Whether and how the genetic lesions detected in patients cause autoimmune bone marrow failure have not yet been determined. We found that mice with spontaneous deletion of the TGFß-activated kinase-1 gene in a small subset of hematopoietic cells developed bone marrow failure which resembled the clinical manifestations of acquired aplastic anemia patients. Bone marrow failure in such mice could be reversed by depletion of CD4+ T lymphocytes or blocked by knockout of interferon-γ, suggesting a Th1-cell-mediated autoimmune mechanism. The onset and progression of bone marrow failure in such mice were significantly accelerated by the inactivation of tumor necrosis factor-α signaling. Tumor necrosis factor-α restricts autoimmune bone marrow failure by inhibiting type-1 T-cell responses and maintaining the function of myeloid-derived suppressor cells. Furthermore, we determined that necroptosis among a small subset of mutant hematopoietic cells is the cause of autoimmune bone marrow failure because such bone marrow failure can be prevented by deletion of receptor interacting protein kinase-3 Our study suggests a novel mechanism to explain the pathogenesis of autoimmune bone marrow failure.
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Apoptosis , Autoinmunidad , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Médula Ósea/inmunología , Médula Ósea/metabolismo , Mutación , Necrosis , Anemia Aplásica/etiología , Anemia Aplásica/metabolismo , Anemia Aplásica/mortalidad , Anemia Aplásica/patología , Animales , Apoptosis/genética , Apoptosis/inmunología , Biomarcadores , Médula Ósea/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Hematopoyesis/genética , Hematopoyesis/inmunología , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/metabolismo , Interferón gamma/deficiencia , Activación de Linfocitos , Quinasas Quinasa Quinasa PAM/genética , Masculino , Ratones , Ratones Noqueados , Necrosis/genética , Necrosis/inmunología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/deficiencia , Transducción de Señal , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
INTRODUCTION: The global healthcare kiosk market is growing, and kiosks are projected to be a larger part of healthcare delivery in the coming decades. We developed an unmanned healthcare kiosk that automates the management of stable patients with chronic conditions to complement face-to-face primary care physician (PCP) visits. AIM: The aim of our study was to show that the kiosk could be a feasible means of delivering care for stable patients with chronic conditions and could generate cost savings for the management of patients with stable chronic disease. METHODS: We conducted a prospective single-arm study of 95 participants with well-controlled chronic cardiovascular diseases who visited our clinic in Singapore every 3 months for review and medication refill. During their subsequent appointments for chronic disease management at 3 and 6 months, participants used the kiosk instead of consulting a physician. All participants who used the kiosk were also evaluated by a nurse clinician (NC). The kiosk assessment of whether the patient was well controlled was then compared to the NC's assessment to determine rates of agreement. Patient satisfaction was evaluated through a questionnaire, and any adverse outcomes were documented. RESULTS: Cohen's κ for agreement between the kiosk and the NC assessment of patients' chronic care control was 0.575 (95% CI, 0.437-0.713). The modest agreement was due to differences in systolic blood pressure measurements between the kiosk and the NC. The 96% of participants who completed two kiosk visits were all satisfied with the kiosk as a care delivery alternative. None of the participants managed through the kiosk suffered any adverse outcomes. Use of the kiosk resulted in a reduction of 128 face-to-face PCP visits. CONCLUSIONS: Healthcare kiosks can potentially be used to complement primary care clinician visits for managing patients with stable chronic diseases and can generate cost savings.
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Instituciones de Atención Ambulatoria , Enfermedades Cardiovasculares/terapia , Satisfacción del Paciente , Atención Primaria de Salud/métodos , Derivación y Consulta , Anciano , Instituciones de Atención Ambulatoria/tendencias , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/psicología , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/tendencias , Estudios Prospectivos , Derivación y Consulta/tendencias , Singapur/epidemiologíaRESUMEN
TTK/Mps1 is a key kinase controlling progression of cell division via participation in the mitotic spindle assembly checkpoint and is overexpressed in a number of human cancers. Herein we report the discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as a potent, novel class of TTK inhibitors. The series was identified by means of bioisosteric replacement of the related imidazopyrazine and imidazopyridazine scaffolds. Optimization led to the identification of compounds with excellent potency (Ki=0.8nM) and exceptional kinase selectivity. The SAR indicates a strong dependence of activity on the presence of the N-cyclopropyl-2-methylbenzamide moiety delineating the geometry for 1½ type kinase inhibitor. Molecular modeling indicates the extensive and optimal contacts, mediated through H-bonds and hydrophobic interactions, are responsible for the selectivity and potency of the inhibitors. The compounds demonstrate a strong anti-proliferative activity in a panel of human cancer cell lines (HCT116 GI50<15nM) and good rodent pharmacokinetics (oral %F 97%).
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Antineoplásicos/farmacología , Benzamidas/farmacología , Proteínas de Ciclo Celular/antagonistas & inhibidores , Descubrimiento de Drogas , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Triazinas/farmacología , Administración Oral , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Benzamidas/administración & dosificación , Benzamidas/química , Disponibilidad Biológica , Proteínas de Ciclo Celular/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Ratas , Relación Estructura-Actividad , Triazinas/administración & dosificación , Triazinas/químicaRESUMEN
An increase in the prevalence of chronic disease has led to a rise in the demand for primary healthcare services in many developed countries. Healthcare technology tools may provide the leverage to alleviate the shortage of primary care providers. Here we describe the development and usage of an automated healthcare kiosk for the management of patients with stable chronic disease in the primary care setting. One-hundred patients with stable chronic disease were recruited from a primary care clinic. They used a kiosk in place of doctors' consultations for two subsequent follow-up visits. Patient and physician satisfaction with kiosk usage were measured on a Likert scale. Kiosk blood pressure measurements and triage decisions were validated and optimized. Patients were assessed if they could use the kiosk independently. Patients and physicians were satisfied with all areas of kiosk usage. Kiosk triage decisions were accurate by the 2nd month of the study. Blood pressure measurements by the kiosk were equivalent to that taken by a nurse (p = 0.30, 0.14). Independent kiosk usage depended on patients' language skills and educational levels. Healthcare kiosks represent an alternative way to manage patients with stable chronic disease. They have the potential to replace physician visits and improve access to primary healthcare. Patients welcome the use of healthcare technology tools, including those with limited literacy and education. Optimization of environmental and patient factors may be required prior to the implementation of kiosk-based technology in the healthcare setting.
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Enfermedad Crónica/terapia , Atención Primaria de Salud/métodos , Interfaz Usuario-Computador , Adulto , Anciano , Glucemia , Determinación de la Presión Sanguínea , Escolaridad , Femenino , Humanos , Lenguaje , Lípidos/sangre , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Proyectos PilotoRESUMEN
TTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50=3.6nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described.
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Amidas/farmacología , Bencenoacetamidas/farmacología , Proteínas de Ciclo Celular/antagonistas & inhibidores , Descubrimiento de Drogas , Indazoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Amidas/síntesis química , Amidas/química , Bencenoacetamidas/síntesis química , Bencenoacetamidas/química , Proteínas de Ciclo Celular/metabolismo , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Humanos , Indazoles/síntesis química , Indazoles/química , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Relación Estructura-ActividadRESUMEN
BACKGROUND AND OBJECTIVES: Under the Merit-Based Incentive Payment System (MIPS), Medicare evaluates provider performance to determine payment adjustments. Studies examining the first year of MIPS (2017) showed that safety-net providers had lower MIPS scores, but the performance of safety-net physicians over time has not been studied. This study aimed to examine the performance of safety-net vs non-safety-net neurosurgeons in MIPS from 2017 to 2020. METHODS: Safety-net neurosurgeons were defined as being in the top quartile according to proportion of dual-eligible beneficiaries and non-safety-net in the bottom quartile. Outcomes were total MIPS scores and dual-eligible proportion over time. In this descriptive study, we evaluated ordinary least squares regression models with SEs clustered at the physician level. Covariates of interest included safety-net status, year, and average Hierarchical Condition Category risk score of beneficiaries. RESULTS: There were 2796-3322 physicians included each year between 2017 and 2020. Mean total MIPS scores were not significantly different for safety-net than non-safety-net physicians in 2017 but were greater for safety-net in 2018 (90.7 vs 84.5, P < .01), 2019 (86.4 vs 81.5, P < .01), and 2020 (90.9 vs 86.7, P < .01). Safety-net status (coefficient -9.11; 95% CI [-13.15, -5.07]; P < .01) and participation in MIPS as an individual (-9.89; [-12.66, -7.13]; P < .01) were associated with lower scores while year, the interaction between safety-net status and year, and participation in MIPS as a physician group or alternative payment model were associated with higher scores. Average Hierarchical Condition Category risk score of beneficiaries (-.011; [-.015, -.006]; P < .01) was associated with decreasing dual-eligible case mix, whereas average age of beneficiaries (.002; [.002, .003]; P < .01) was associated with increasing dual-eligible case mix. CONCLUSION: Being a safety-net physician was associated with lower MIPS scores, but safety-net neurosurgeons demonstrated greater improvement in MIPS scores than non-safety-net neurosurgeons over time. Providers with higher-risk patients were more likely to decrease their dual-eligible case mix over time.
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Adolescence is a challenging time at baseline, and a sibling receiving end-of-life care can alter an adolescent's life irrevocably. It is imperative for the medical team to understand the unique needs and perspectives of such an adolescent sibling. This in turn facilitates the anticipation of an adolescent's grief response, and allows for parents to be appropriately guided. However, more can be done to evaluate the needs of adolescent siblings and improve their support. This can be through establishing a validated needs-based questionnaire, empowering families and the multidisciplinary team to engage siblings, and diverting resources toward culturally sensitive support groups for siblings with critical illness. A framework to involve key players in the adolescent's circle is presented.
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Introduction: Advancement in medical expertise and technology has led to a growing cohort of children with medical complexity (CMC), who make up a rising proportion of childhood deaths. However, end of life in CMC is poorly understood and little is known about illness trajectories, communication, and decision-making experiences. Objective: To synthesize existing literature and characterize the end-of-life experience in CMC. Methods: A literature search of MEDLINE, CINAHL, PsycINFO, Scopus, Embase, and Google Scholar was conducted up to August 26, 2021. Studies reporting CMC at end of life were included and the extracted data were analyzed descriptively. Findings: Of 1535 publications identified, 23 studies were included. Most studies (15/23 [65%]) were published from 2015 to 2021 and were quantitative in nature (20/23 [87%]). The majority of studies that extracted data from a single country (18/20 [90%]) originated from North America. Study outcomes were categorized into four main domains: (1) place of death (2) health care use (3) interventions received or withdrawn (4) communication, and end-of-life experiences. The weighted percentage of in-hospital CMC deaths was 80.6%. Studies reported that CMC had increased health care use and were subjected to more intensive interventions at end of life compared with non-CMC. Qualitative studies highlighted the following themes: Intrinsic prognostic uncertainty, differing perspectives of the child's quality of life, the chronic illness experience, a desire to have parental expertise acknowledged, surprise at the terminal event, the experience of multiple losses, with an overarching theme of the need for compassionate care at end of life. Conclusions: This scoping review highlighted important characteristics of end of life in CMC, outlining the emerging evidence and knowledge gaps on this topic. A better understanding of this cohort of seriously and chronically ill children would serve to inform clinical practice, service development, and future research.
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Adults with intellectual and developmental disabilities (IDD) are increasingly living into adulthood, highlighting the need for adult clinicians to expand their familiarity with congenital conditions. Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive inborn error of cholesterol synthesis. SLOS is commonly diagnosed in childhood, but a number of adults with IDD progress into adulthood without a formal diagnosis. We present an 18-year-old male with a history of IDD and altered pain sensation who was hospitalized following a self-inflicted knife injury resulting in a traumatic ventricular septal defect. Over the following 15 years, the patient continued to exhibit self-injurious behaviors. At the age of 33, caregivers consented to further work-up of his intellectual disability, and whole-exome genetic sequencing revealed a diagnosis of SLOS. The clinical course of this patient represents a unique presentation of altered pain sensation, a delayed diagnosis of SLOS into adulthood, and the challenges of providing care to an adult with IDD. The case further highlights the importance of understanding the typical workup and management of genetic and congenital conditions arising in childhood.
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OBJECTIVE: To determine whether mandatory participation by hospitals in bundled payments for lower extremity joint replacement (LEJR) was associated with changes in outcome disparities for patients dually eligible for Medicare and Medicaid. DATA SOURCES AND STUDY SETTING: We used Medicare claims data for beneficiaries undergoing LEJR in the United States between 2011 and 2017. STUDY DESIGN: We conducted a retrospective observational study using a differences-in-differences method to compare changes in outcome disparities between dual-eligible and non-dual eligible beneficiaries after hospital participation in the Comprehensive Care for Joint Replacement (CJR) program. The primary outcome was LEJR complications. Secondary outcomes included 90-day readmissions and mortality. DATA EXTRACTION METHODS: We identified hospitals in the US market areas eligible for CJR. We included beneficiaries in the intervention group who received joint replacement at hospitals in markets randomized to participate in CJR. The comparison group included patients who received joint replacement at hospitals in markets who were eligible for CJR but randomized to control. PRINCIPAL FINDINGS: The study included 1,603,555 Medicare beneficiaries (mean age, 74.6 years, 64.3% women, 11.0% dual-eligible). Among participant hospitals, complications decreased between baseline and intervention periods from 11.0% to 10.1% for dual-eligible and 7.0% to 6.4% for non-dual-eligible beneficiaries. Among nonparticipant hospitals, complications decreased from 10.3% to 9.8% for dual-eligible and 6.7% to 6.0% for non-dual-eligible beneficiaries. In adjusted analysis, CJR participation was associated with a reduced difference in complications between dual-eligible and non-dual-eligible beneficiaries (-0.9 percentage points, 95% CI -1.6 to -0.1). The reduction in disparities was observed among hospitals without prior experience in a voluntary LEJR bundled payment model. There were no differential changes in 90-day readmissions or mortality. CONCLUSIONS: Mandatory participation in a bundled payment program was associated with reduced disparities in joint replacement complications for Medicare beneficiaries with low income. To our knowledge, this is the first evidence of reduced socioeconomic disparities in outcomes under value-based payments.
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Cell type identification is one of the fundamental tasks in single-cell RNA sequencing (scRNA-seq) studies. It is a key step to facilitate downstream interpretations such as differential expression, trajectory inference, etc. scRNA-seq data contains technical variations that could affect the interpretation of the cell types. Therefore, gene selection, also known as feature selection in data science, plays an important role in selecting informative genes for scRNA-seq cell type identification. Generally speaking, feature selection methods are categorized into filter-, wrapper-, and embedded-based approaches. From the existing literature, methods from filter- and embedded-based approaches are widely applied in scRNA-seq gene selection tasks. The wrapper-based method that gives promising results in other fields has yet been extensively utilized for selecting gene features from scRNA-seq data; in addition, most of the existing wrapper methods used in this field are clustering instead of classification-based. With a large number of annotated data available today, this study applied a classification-based approach as an alternative to the clustering-based wrapper method. In our work, a quantum-inspired differential evolution (QDE) wrapped with a classification method was introduced to select a subset of genes from twelve well-known scRNA-seq transcriptomic datasets to identify cell types. In particular, the QDE was combined with different machine-learning (ML) classifiers namely logistic regression, decision tree, support vector machine (SVM) with linear and radial basis function kernels, as well as extreme learning machine. The linear SVM wrapped with QDE, namely QDE-SVM, was chosen by referring to the feature selection results from the experiment. QDE-SVM showed a superior cell type classification performance among QDE wrapping with other ML classifiers as well as the recent wrapper methods (i.e., FSCAM, SSD-LAHC, MA-HS, and BSF). QDE-SVM achieved an average accuracy of 0.9559, while the other wrapper methods achieved average accuracies in the range of 0.8292 to 0.8872.
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Análisis de Expresión Génica de una Sola Célula , Máquina de Vectores de Soporte , Perfilación de la Expresión Génica/métodos , Transcriptoma , Aprendizaje Automático , Análisis por Conglomerados , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , AlgoritmosRESUMEN
INTRODUCTION: The relationship between socioeconomic status and neurosurgical outcomes has been investigated with respect to insurance status or median household income, but few studies have considered more comprehensive measures of socioeconomic status. This study examines the relationship between Area Deprivation Index (ADI), a comprehensive measure of neighborhood socioeconomic disadvantage, and short-term postoperative outcomes after lumbar fusion surgery. METHODS: 1861 adult patients undergoing single-level, posterior-only lumbar fusion at a single, multihospital academic medical center were retrospectively enrolled. An ADI matching protocol was used to identify each patient's 9-digit zip code and the zip code-associated ADI data. Primary outcomes included 30- and 90-day readmission, emergency department visits, reoperation, and surgical complication. Coarsened exact matching was used to match patients on key demographic and baseline characteristics known to independently affect neurosurgical outcomes. Odds ratios (ORs) were computed to compare patients in the top 10% of ADI versus lowest 40% of ADI. RESULTS: After matching (n = 212), patients in the highest 10% of ADI (compared to the lowest 40% of ADI) had significantly increased odds of 30- and 90-day readmission (OR = 5.00, P < 0.001 and OR = 4.50, P < 0.001), ED visits (OR = 3.00, P = 0.027 and OR = 2.88, P = 0.007), and reoperation (OR = 4.50, P = 0.039 and OR = 5.50, P = 0.013). There was no significant association with surgical complication (OR = 0.50, P = 0.63). CONCLUSIONS: Among otherwise similar patients, neighborhood socioeconomic disadvantage (measured by ADI) was associated with worse short-term outcomes after single-level, posterior-only lumbar fusion. There was no significant association between ADI and surgical complications, suggesting that perioperative complications do not explain the socioeconomic disparities in outcomes.
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Centros Médicos Académicos , Disparidades Socioeconómicas en Salud , Adulto , Humanos , Estudios Retrospectivos , Reoperación , Segunda Cirugía , Factores SocioeconómicosRESUMEN
OBJECTIVE: There are limited data evaluating the outcomes of attending neurosurgeons with different types of first assistants. This study considers a common neurosurgical procedure (single-level, posterior-only lumbar fusion surgery) and examines whether attending surgeons deliver equal patient outcomes, regardless of the type of first assistant (resident physician vs. nonphysician surgical assistant [NPSA]), among otherwise exact-matched patients. METHODS: The authors retrospectively analyzed 3395 adult patients undergoing single-level, posterior-only lumbar fusion at a single academic medical center. Primary outcomes included readmissions, emergency department visits, reoperation, and mortality within 30 and 90 days after surgery. Secondary outcome measures included discharge disposition, length of stay, and length of surgery. Coarsened exact matching was used to match patients on key demographics and baseline characteristics known to independently affect neurosurgical outcomes. RESULTS: Among exact-matched patients (n = 1402), there was no significant difference in adverse postsurgical events (readmission, emergency department visits, reoperation, or mortality) within 30 days or 90 days of the index operation between patients who had resident physicians and those who had NPSAs as first assistants. Patients who had resident physicians as first assistants demonstrated a longer length of stay (mean: 100.0 vs. 87.4 hours, P < 0.001) and a shorter duration of surgery (mean: 187.4 vs. 213.8 minutes, P < 0.001). There was no significant difference between the two groups in the percentage of patients discharged home. CONCLUSIONS: For single-level posterior spinal fusion, in the setting described, there are no differences in short-term patient outcomes delivered by attending surgeons assisted by resident physicians versus NPSAs.
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Fusión Vertebral , Cirujanos , Adulto , Humanos , Neurocirujanos , Estudios Retrospectivos , Calidad de la Atención de Salud , Reoperación , Fusión Vertebral/efectos adversos , Complicaciones Posoperatorias/etiología , Vértebras Lumbares/cirugíaRESUMEN
BACKGROUND: Loss of control (LOC) eating, the subjective sense that one cannot control what or how much one eats, characterizes binge-eating behaviors pervasive in obesity and related eating disorders. Closed-loop deep-brain stimulation (DBS) for binge eating should predict LOC and trigger an appropriately timed intervention. OBJECTIVE/HYPOTHESIS: This study aimed to identify a sensitive and specific biomarker to detect LOC onset for DBS. We hypothesized that changes in phase-locking value (PLV) predict the onset of LOC-associated cravings and distinguish them from potential confounding states. METHODS: Using DBS data recorded from the nucleus accumbens (NAc) of two patients with binge eating disorder (BED) and severe obesity, we compared PLV between inter- and intra-hemispheric NAc subregions for three behavioral conditions: craving (associated with LOC eating), hunger (not associated with LOC), and sleep. RESULTS: In both patients, PLV in the high gamma frequency band was significantly higher for craving compared to sleep and significantly higher for hunger compared to craving. Maximum likelihood classifiers achieved accuracies above 88% when differentiating between the three conditions. CONCLUSIONS: High-frequency inter- and intra-hemispheric PLV in the NAc is a promising biomarker for closed-loop DBS that differentiates LOC-associated cravings from physiologic states such as hunger and sleep. Future trials should assess PLV as a LOC biomarker across a larger cohort and a wider patient population transdiagnostically.
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Bulimia , Humanos , Conducta Alimentaria , Obesidad , Núcleo Accumbens , BiomarcadoresRESUMEN
BACKGROUND: The role of emergency department resuscitative thoracotomy (EDT) in traumatically injured children has not been elucidated. We aimed to perform a systematic review and create evidence-based guidelines to answer the following PICO (population, intervention, comparator, and outcome) question: should pediatric patients who present to the emergency department pulseless (with or without signs of life [SOL]) after traumatic injuries (penetrating thoracic, penetrating abdominopelvic, or blunt) undergo EDT (vs. no EDT) to improve survival and neurologically intact survival? METHODS: Using Grading of Recommendations Assessment, Development and Evaluation methodology, a group of 12 pediatric trauma experts from the Pediatric Trauma Society, Western Trauma Association, and Eastern Association for the Surgery of Trauma assembled to perform a systematic review. A consensus conference was conducted, a database was queried, abstracts and manuscripts were reviewed, data extraction was performed, and evidence quality was determined. Evidence tables were generated, and the committee voted on guideline recommendations. RESULTS: Three hundred three articles were identified. Eleven studies met the inclusion criteria and were used for guideline creation, providing 319 pediatric patients who underwent EDT. No data were available on patients who did not undergo EDT. For each PICO, the quality of evidence was very low based on the serious risk of bias and serious or very serious imprecision. CONCLUSION: Based on low-quality data, we make the following recommendations. We conditionally recommend EDT when a child presents pulseless with SOL to the emergency department following penetrating thoracic injury, penetrating abdominopelvic injury and after blunt injury if emergency adjuncts point to a thoracic source. We conditionally recommend against EDT when a pediatric patient presents pulseless without SOL after penetrating thoracic and penetrating abdominopelvic injury. We strongly recommend against EDT in the patient without SOL after blunt injury.
Asunto(s)
Heridas no Penetrantes , Heridas Penetrantes , Niño , Humanos , Consenso , Servicio de Urgencia en Hospital , Toracotomía , Heridas no Penetrantes/cirugía , Heridas Penetrantes/cirugía , Revisiones Sistemáticas como Asunto , Guías de Práctica Clínica como AsuntoRESUMEN
Objectives: The risk factors for anastomotic leak (AL) after resection and primary anastomosis for traumatic bucket handle injury (BHI) have not been previously defined. This multicenter study was conducted to address this knowledge gap. Methods: This is a multicenter retrospective study on small intestine and colonic BHIs from blunt trauma between 2010 and 2021. Baseline patient characteristics, risk factors, presence of shock and transfusion, operative details, and clinical outcomes were compared using R. Results: Data on 395 subjects were submitted by 12 trauma centers, of whom 33 (8.1%) patients developed AL. Baseline details were similar, except for a higher proportion of patients in the AL group who had medical comorbidities such as diabetes, hypertension, and obesity (60.6% vs. 37.3%, p=0.015). AL had higher rates of surgical site infections (13.4% vs. 5.3%, p=0.004) and organ space infections (65.2% vs. 11.7%, p<0.001), along with higher readmission and reoperation rates (48.4% vs. 9.1%, p<0.001, and 39.4% vs. 11.6%, p<0.001, respectively). There was no difference in intensive care unit length of stay or mortality (p>0.05). More patients with AL were discharged with an ostomy (69.7% vs. 7.3%, p<0.001), and the mean duration until ostomy reversal was 5.85±3 months (range 2-12.4 months). The risk of AL significantly increased when the initial operation was a damage control procedure, after adjusting for age, sex, injury severity, presence of one or more comorbidities, shock, transfusion of >6 units of packed red blood cells, and site of injury (adjusted RR=2.32 (1.13, 5.17)), none of which were independent risk factors in themselves. Conclusion: Damage control surgery performed as the initial operation appears to double the risk of AL after intestinal BHI, even after controlling for other markers of injury severity. Level of evidence: III.