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1.
Appl Neuropsychol Adult ; : 1-10, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527375

RESUMO

Quantifying learning deficits provides valuable information in identifying and diagnosing mild cognitive impairment and dementia. Previous research has found that a learning ratio (LR) metric, derived from the list learning test from the Neuropsychological Assessment Battery (NAB), was able to distinguish between those with normal cognition versus memory impairment. The current study furthers the NAB LR research by validating a NAB story LR, as well as an aggregate LR. The aggregate LR was created by combining the individual list and story LRs. Participants were classified as those with normal cognition (n = 51), those with MCI (n = 39) and those with dementia (n = 35). Results revealed the story LR was able to accurately distinguish normal controls from those with mild cognitive impairment and those with dementia and offers enhanced discriminability beyond the story immediate recall score (sum of trial 1 and trial 2). Further, the aggregate LR provided superior discriminability beyond the individual list and story LRs and accounted for additional variance in diagnostic group classification. The NAB aggregate LR provides improved sensitivity in detecting declines in impaired learning, which may assist clinicians in making diagnoses earlier in a disease process, benefiting the individual through earlier interventions.

2.
J Pediatr Gastroenterol Nutr ; 78(5): 1180-1189, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38506111

RESUMO

OBJECTIVES: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors. METHODS: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service. RESULTS: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available. CONCLUSIONS: One-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Acessibilidade aos Serviços de Saúde , Hospitais Pediátricos , Humanos , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Criança , Hospitais Pediátricos/estatística & dados numéricos , Masculino , Feminino , Estados Unidos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Pré-Escolar , Adolescente , Lactente , Pancreatopatias/terapia , Pancreatopatias/cirurgia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Doenças Biliares/terapia , Estudos Retrospectivos
3.
Health Aff (Millwood) ; 43(2): 172-180, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38315921

RESUMO

This article examines racial and ethnic disparities in the relationship between gentrification and exposure to contextual determinants of health. In our study, we focused on changes in selected contextual determinants of health (health care access, social deprivation, air pollution, and walkability) and life expectancy during the period 2006-21 among residents of gentrifying census tracts in six large US cities that have experienced different gentrification patterns and have different levels of segregation: Chicago, Illinois; Los Angeles, California; New York, New York; Philadelphia, Pennsylvania; San Francisco, California; and Seattle, Washington. We found that gentrification was associated with overall improvements in the likelihood of living in Medically Underserved Areas across racial and ethnic groups, but it was also associated with increased social deprivation and reduced life expectancy among Black people, Hispanic people, and people of another or undetermined race or ethnicity. In contrast, we found that gentrification was related to better (or unchanged) contextual determinants of health for Asian people and White people. Our findings can inform policies that target communities identified to be particularly at risk for worsening contextual determinants of health as a result of gentrification.


Assuntos
Etnicidade , Desigualdades de Saúde , Segregação Residencial , Determinantes Sociais da Saúde , Humanos , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Philadelphia/epidemiologia , Brancos/estatística & dados numéricos , Determinantes Sociais da Saúde/etnologia , Determinantes Sociais da Saúde/estatística & dados numéricos , Estados Unidos/epidemiologia , Asiático/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Expectativa de Vida/etnologia , Expectativa de Vida/tendências , Características de Residência/estatística & dados numéricos , Grupos Raciais/etnologia , Grupos Raciais/estatística & dados numéricos
4.
JAMA Netw Open ; 7(2): e2355707, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38349656

RESUMO

Importance: There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement. Objectives: To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug. Design, Setting, and Participants: This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022. Main Outcomes and Measures: PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs. Results: The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019. Conclusions and Relevance: In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.


Assuntos
Medicaid , Testes Farmacogenômicos , Masculino , Estados Unidos , Humanos , Adolescente , Pré-Escolar , Criança , Estudos Transversais , Citocromo P-450 CYP2D6 , Bases de Dados Factuais
5.
Proc Biol Sci ; 291(2014): 20231273, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38196353

RESUMO

The relationship between pathogen proliferation and the cost of infection experienced by a host drives the ecology and evolution of host-pathogen dynamics. While environmental factors can shape this relationship, there is currently limited knowledge on the consequences of emerging contaminants, such as pharmaceutical pollutants, on the relationship between a pathogen's growth within the host and the damage it causes, termed its virulence. Here, we investigated how exposure to fluoxetine (Prozac), a commonly detected psychoactive pollutant, could alter this key relationship using the water flea Daphnia magna and its bacterial pathogen Pasteuria ramosa as a model system. Across a variety of fluoxetine concentrations, we found that fluoxetine shaped the damage a pathogen caused, such as the reduction in fecundity or intrinsic growth experienced by infected individuals, but with minimal change in average pathogen spore loads. Instead, fluoxetine modified the relationship between the degree of pathogen proliferation and its virulence, with both the strength of this trade-off and the component of host fitness most affected varying by fluoxetine concentration and host genotype. Our study underscores the potential for pharmaceutical pollution to modify the virulence of an invading pathogen, as well as the fundamental trade-off between host and pathogen fitness, even at the trace amounts increasingly found in natural waterways.


Assuntos
Infecções Bacterianas , Daphnia magna , Poluentes Ambientais , Animais , Poluição Ambiental , Fluoxetina , Preparações Farmacêuticas , Daphnia magna/microbiologia
6.
JAMA Pediatr ; 178(2): 185-192, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109092

RESUMO

Importance: Public benefit programs, including state spending on local, state, and federal-state partnership programs, have consistently been associated with overall reductions in child protective services (CPS) involvement. Inequities in eligibility and access to benefit programs may contribute to varying associations by race and ethnicity. Objective: To determine whether associations between state spending on benefit programs and rates of CPS investigations differ by race and ethnicity. Design, Setting, and Participants: This cross-sectional ecological study used repeated state-level measures of child maltreatment from the National Child Abuse and Neglect Data System and population estimates from the US Census Bureau for all Black, Hispanic, and White children. All 50 US states from October 1, 2009, through September 30, 2019 (fiscal years 2010-2019), were included. Data were collected and analyzed from May 13, 2022, to March 2, 2023. Exposures: Annual state spending on benefit programs per person living below the federal poverty limit, total and by the following subcategories: (1) cash, housing, and in-kind; (2) housing infrastructure; (3) child care assistance; (4) refundable earned income tax credit; and (5) medical assistance programs. Main Outcomes and Measures: Race- and ethnicity-specific rates of CPS investigations. Generalized estimating equations, with repeated measures of states, an interaction between race and spending, and estimated incidence rate ratios (IRRs) and 95% CIs for incremental changes in spending of US $1000 per person living below the federal poverty limit were calculated after adjustment for federal spending, race- and ethnicity-specific child poverty rate, and year. Results: A total of 493 state-year observations were included in the analysis. The association between total spending and CPS investigations differed significantly by race and ethnicity: there was an inverse association between total state spending and CPS investigations for White children (IRR, 0.94 [95% CI, 0.91-0.98]) but not for Black children (IRR, 0.98 [95% CI, 0.94-1.02]) or Hispanic children (IRR, 0.99 [95% CI, 0.95-1.03]) (P = .02 for interaction). Likewise, inverse associations were present for only White children with respect to all subcategories of state spending and differed significantly from Black and Hispanic children for all subcategories except the refundable earned income tax credit (eg, IRR for medical assistance programs for White children, 0.89 [95% CI, 0.82-0.96]; P = .005 for race and spending interaction term). Conclusions and Relevance: These results raise concerns that benefit programs may add relative advantages for White children compared with Black and Hispanic children and contribute to racial and ethnic disparities in CPS investigations. States' eligibility criteria and distribution practices should be examined to promote equitable effects on adverse child outcomes.


Assuntos
Maus-Tratos Infantis , Etnicidade , Assistência Pública , Criança , Humanos , Maus-Tratos Infantis/economia , Maus-Tratos Infantis/etnologia , Maus-Tratos Infantis/estatística & dados numéricos , Estudos Transversais , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Pobreza/etnologia , Pobreza/estatística & dados numéricos , Estados Unidos/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Brancos/estatística & dados numéricos , Assistência Pública/economia , Assistência Pública/estatística & dados numéricos
7.
J Homosex ; 71(1): 120-146, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35984389

RESUMO

This article explores the contribution agent-based modeling (ABM) can make to the study of LGBTQ workplace inequalities and, conversely, how ABM can adapt to theoretical traditions integral to LGBTQ studies. It introduces an example LGBTQ workplace model, developed as part of the CILIA-LGBTQI+ project, to illustrate how ABM complements existing methods, can address methodological binarism and bridge macro and micro accounts within LGBTQ studies of the workplace. The model is intended as an important starting point in developing the role of ABM in LGBTQ research and for bridging qualitative- and quantitative-derived insights. Likewise, the article discusses some approaches for negotiating theoretical and methodological tensions identified when integrating queer and intersectional insight with ABM.


Assuntos
Minorias Sexuais e de Gênero , Humanos , Identidade de Gênero , Local de Trabalho , Negociação
8.
Pediatrics ; 153(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38130171

RESUMO

BACKGROUND AND OBJECTIVES: Longitudinal pediatric low-value care (LVC) trends are not well established. We used the Pediatric Health Information System LVC Calculator, which measures utilization of 30 nonevidenced-based services, to report 7-year LVC trends. METHODS: This retrospective cohort study applied the LVC Calculator to emergency department (ED) and hospital encounters from January 1, 2016, to December 31, 2022. We used generalized estimating equation models accounting for hospital clustering to assess temporal changes in LVC. RESULTS: There were 5 265 153 eligible ED encounters and 1 301 613 eligible hospitalizations. In 2022, of 21 LVC measures applicable to the ED cohort, the percentage of encounters with LVC had increased for 11 measures, decreased for 1, and remained unchanged for 9 as compared with 2016. Computed tomography for minor head injury had the largest increase (17%-23%; P < .001); bronchodilators for bronchiolitis decreased (22%-17%; P = .001). Of 26 hospitalization measures, LVC increased for 6 measures, decreased for 9, and was unchanged for 11. Inflammatory marker testing for pneumonia had the largest increase (23%-38%; P = .003); broad-spectrum antibiotic use for pneumonia had the largest decrease (60%-48%; P < .001). LVC remained unchanged or decreased for most medication and procedure measures, but remained unchanged or increased for most laboratory and imaging measures. CONCLUSIONS: LVC improved for a minority of services between 2016 and 2022. Trends were more favorable for therapeutic (medications and procedures) than diagnostic measures (imaging and laboratory studies). These data may inform prioritization of deimplementation efforts.


Assuntos
Cuidados de Baixo Valor , Pneumonia , Criança , Humanos , Estudos Retrospectivos , Hospitalização , Serviço Hospitalar de Emergência , Hospitais Pediátricos
9.
Proc Natl Acad Sci U S A ; 120(40): e2311005120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748055

RESUMO

Over the last decade, the United States has seen increasing antidemocratic rhetoric by political leaders. Yet, prior work suggests that such norm-violating rhetoric does not undermine support for democracy as a system of government. We argue that, while that may be true, such rhetoric does vitiate support for specific democratic principles. We test this theory by extending prior work to assess the effects of Trump's norm-violating rhetoric on general support for democracy as well as for the principles of participatory inclusiveness, contestation, the rule of law, and political equality. We find that Trump's rhetoric does not alter attitudes toward democracy as a preferred system but does reduce support for inclusiveness and equality among his supporters. Our findings suggest that elite rhetoric can undermine basic principles of American democracy.


Assuntos
Governo , Software
10.
Pediatrics ; 152(2)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37431596

RESUMO

BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics endorses screening for social determinants of health (SDOH) and providing families resources for unmet needs. A systematic response to unmet needs requires identification, documentation, and provision of resources. Our goal was to compare SDOH International Classification of Diseases, 10th Revision (ICD-10), code use for pediatric inpatients after policy changes in 2018 permitting coding by nonphysicians. METHODS: We conducted a retrospective cohort study comparing data from the 2016 and 2019 Kid's Inpatient Database for patients <21 years old. The primary variable was the presence of an SDOH code, defined as an ICD-10 Z-code (Z55-Z65) or 1 of 13 ICD-10 codes recommended by the American Academy of Pediatrics. We compared overall SDOH code usage between 2016 and 2019, and by Z-code category, demographic, clinical, and hospital characteristics using χ2 tests and odds ratios. Using logistic regression, we examined hospital-level characteristics for hospitals with >5% of discharges with an SDOH code. RESULTS: SDOH code documentation increased from 1.4% in 2016 to 1.9% in 2019 (P < .001), with no notable differences based on Z-code category. In both periods, SDOH code documentation was more common in adolescents, Native Americans, and patients with mental health diagnoses. The number of all hospitals using any SDOH code increased nearly 8% between 2016 and 2019. CONCLUSIONS: ICD-10 codes remain underused to track SDOH needs within the inpatient pediatric setting. Future research should explore whether SDOH code documentation is associated with increased response to unmet social needs and, if so, how to improve use of SDOH codes by all providers.

11.
JAMA Netw Open ; 6(5): e2311752, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37140920

RESUMO

Importance: Government and commercial health insurers have recently enacted policies to discourage nonemergent emergency department (ED) visits by reducing or denying claims for such visits using retrospective claims algorithms. Low-income Black and Hispanic pediatric patients often experience worse access to primary care services necessary for preventing some ED visits, raising concerns about the uneven impact of these policies. Objective: To estimate potential racial and ethnic disparities in outcomes of Medicaid policies for reducing ED professional reimbursement based on a retrospective diagnosis-based claims algorithm. Design, Setting, and Participants: This simulation study used a retrospective cohort of pediatric ED visits (aged 0-18 years) for Medicaid-insured children and adolescents appearing in the Market Scan Medicaid database between January 1, 2016, and December 31, 2019. Visits missing date of birth, race and ethnicity, professional claims data, and Current Procedural Terminology codes of billing level of complexity were excluded, as were visits that result in admission. Data were analyzed from October 2021 to June 2022. Main Outcomes and Measures: Proportion of ED visits algorithmically classified as nonemergent and simulated per-visit professional reimbursement after applying a current reimbursement reduction policy for potentially nonemergent ED visits. Rates were calculated overall and compared by race and ethnicity. Results: The sample included 8 471 386 unique ED visits (43.0% by patients aged 4-12 years; 39.6% Black, 7.7% Hispanic, and 48.7% White), of which 47.7% were algorithmically identified as potentially nonemergent and subject to reimbursement reduction, resulting in a 37% reduction in ED professional reimbursement across the study cohort. More visits by Black (50.3%) and Hispanic (49.0%) children were algorithmically identified as nonemergent when compared with visits by White children (45.3%; P < .001). Modeling the impact of the reimbursement reductions across the cohort resulted in expected per-visit reimbursement that was 6% lower for visits by Black children and 3% lower for visits by Hispanic children relative to visits by White children. Conclusions and Relevance: In this simulation study of over 8 million unique ED visits, algorithmic approaches for classifying pediatric ED visits that used diagnosis codes identified proportionately more visits by Black and Hispanic children as nonemergent. Insurers applying financial adjustments based on these algorithmic outputs risk creating uneven reimbursement policies across racial and ethnic groups.


Assuntos
Serviço Hospitalar de Emergência , Seguradoras , Adolescente , Estados Unidos , Humanos , Criança , Estudos Retrospectivos , Etnicidade , Medicaid
14.
J Contin Educ Health Prof ; 43(1): 68-71, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36070405

RESUMO

INTRODUCTION: Medical educators in residency programs have unique opportunities to teach health inequities, social determinants of health (SDOH), and implicit bias. However, faculty are not adequately trained to effectively teach these topics. The aim is to assess the effectiveness of a faculty-level workshop to teach health inequity. METHODS: An interactive workshop was designed by an interprofessional faculty from a major urban teaching hospital, addressing SDOH, implicit bias, an "Enhanced Social History," and the benefits of interprofessional care. Before and after completion, workshop participants completed surveys regarding comfort in teaching these concepts. Survey results were analyzed to assess benefits of the intervention. RESULTS: Sixty-four percent of participants completed preworkshop and postworkshop surveys. Participants reported increased contemplation and improved comfort in teaching SDOH, barriers to medical care, and implicit bias. CONCLUSION: Faculty comfort in teaching health inequity increased after this workshop. This may help bridge the gap between the expectation of clinical faculty to evaluate trainee practice of patient-centered, culturally competent care, and faculty possession of and confidence in health inequity teaching skills in clinical settings. Future research should focus on learner- and patient-based outcomes, including teaching time and impact on delivery of care.


Assuntos
Docentes , Internato e Residência , Humanos , Inquéritos e Questionários , Ensino , Docentes de Medicina/educação
15.
J Hand Surg Asian Pac Vol ; 27(5): 845-851, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36178413

RESUMO

Background: The objective of this study was to determine whether economic well-being is associated with patient-reported functional outcomes and range of motion 1 year following volar plate fixation of distal radius fracture. Methods: A retrospective study was performed on 200 patients with distal radius fractures treated with volar plate fixation at two Level 1 trauma centres from 2006 to 2017 with 1-year clinical follow-up using a previously published cohort. The economic well-being of patients was assessed using the Distressed Communities Index (DCI). Our outcome variables were patient-reported functional outcomes assessed by QuickDASH score and wrist and forearm range of motion 1 year after surgery. The analysis of variance (ANOVA) test was used to compare outcome variables across pre-established tiers of economic well-being. Results: The mean QuickDASH score at 1 year following distal radius fracture volar plate fixation was 10.8 and ranged from 7.3 to 12.2 across tiers of economic well-being. QuickDASH score and wrist range of motion were not significantly different across all tiers of economic well-being. However, wrist flexion-extension arc at 1 year following surgery was significantly decreased in the economically at-risk group compared with the remaining cohort. Conclusions: Patient-reported functional outcomes 1 year after volar plate fixation of distal radius fracture are similar across tiers of economic well-being. Economically disadvantaged patients are at risk for poorer wrist motion following distal radius fracture surgery, though it is not clear if this difference is clinically significant. Level of Evidence: Level II (Prognostic).


Assuntos
Fraturas do Rádio , Humanos , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Fraturas do Rádio/etiologia , Fixação Interna de Fraturas/efeitos adversos , Estudos Retrospectivos , Placas Ósseas/efeitos adversos , Articulação do Punho
16.
J Exp Clin Cancer Res ; 41(1): 282, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151566

RESUMO

BACKGROUND: Adrenocortical cancer (ACC) is a rare and aggressive cancer with dismal 5-year survival due to a lack of effective treatments. We aimed to identify a new effective combination of drugs and investigated their synergistic efficacy in ACC preclinical models. METHODS: A quantitative high-throughput drug screening of 4,991 compounds was performed on two ACC cell lines, SW13 and NCI-H295R, based on antiproliferative effect and caspase-3/7 activity. The top candidate drugs were pairwise combined to identify the most potent combinations. The synergistic efficacy of the selected inhibitors was tested on tumorigenic phenotypes, such as cell proliferation, migration, invasion, spheroid formation, and clonogenicity, with appropriate mechanistic validation by cell cycle and apoptotic assays and protein expression of the involved molecules. We tested the efficacy of the drug combination in mice with luciferase-tagged human ACC xenografts. To study the mRNA expression of target molecules in ACC and their clinical correlations, we analyzed the Gene Expression Omnibus and The Cancer Genome Atlas. RESULTS: We chose the maternal embryonic leucine zipper kinase (MELK) inhibitor (OTS167) and cyclin-dependent kinase (CDK) inhibitor (RGB-286638) because of their potent synergy from the pairwise drug combination matrices derived from the top 30 single drugs. Multiple publicly available databases demonstrated overexpression of MELK, CDK1/2, and partnering cyclins mRNA in ACC, which were independently associated with mortality and other adverse clinical features. The drug combination demonstrated a synergistic antiproliferative effect on ACC cells. Compared to the single-agent treatment groups, the combination treatment increased G2/M arrest, caspase-dependent apoptosis, reduced cyclins A2, B1, B2, and E2 expression, and decreased cell migration and invasion with reduced vimentin. Moreover, the combination effectively decreased Foxhead Box M1, Axin2, glycogen synthase kinase 3-beta, and ß-catenin. A reduction in p-stathmin from the combination treatment destabilized microtubule assembly by tubulin depolymerization. The drug combination treatment in mice with human ACC xenografts resulted in a significantly lower tumor burden than those treated with single-agents and vehicle control groups. CONCLUSIONS: Our preclinical study revealed a novel synergistic combination of OTS167 and RGB-286638 in ACC that effectively targets multiple molecules associated with ACC aggressiveness. A phase Ib/II clinical trial in patients with advanced ACC is therefore warranted.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/metabolismo , Animais , Apoptose , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Quinases Ciclina-Dependentes , Ciclinas , Pontos de Checagem da Fase G2 do Ciclo Celular , Quinase 3 da Glicogênio Sintase/farmacologia , Quinase 3 da Glicogênio Sintase/uso terapêutico , Humanos , Camundongos , Proteínas Serina-Treonina Quinases , Pirazóis , RNA Mensageiro , Estatmina , Tubulina (Proteína) , Ureia/análogos & derivados , Vimentina , beta Catenina
17.
Urology ; 162: 84-90, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34000277

RESUMO

OBJECTIVE: To characterize elective, post-neonatal operative circumcision at US children's hospitals, in the context of established sociodemographic disparities in access to neonatal circumcision. METHODS: A retrospective cohort study was performed of boys undergoing elective, operative circumcision at the 23 Pediatric Health Information System (PHIS) hospitals who contributed data from 2004-2018. Boys > = 36 months' and those with congenital anomalies of the penis were excluded. Bivariate statistics were used to compare the circumcision cohort to a referent cohort of boys undergoing other ambulatory surgery or having an observational hospital stay. RESULTS: The annual median number of operative circumcisions per hospital increased during the study (72 [IQR 54-162] to 136 [IQR 88-266], P = .003). Boys undergoing circumcision were mostly non-Hispanic White (46.7%) or non-Hispanic Black (30.9%), in the lowest income quartile (26.6%), from the Southern US (51.5%), and publicly-insured (60.5%). When compared to the reference cohort, boys undergoing circumcision were more likely to be non-Hispanic Black (30.9 vs 15.7%, P = .001) and publicly-insured (60.5 vs 45.9%, P = . 001). CONCLUSION: The number of post-neonatal operative circumcisions performed at US children's hospitals nearly doubled from 2004 to 2018. Study findings suggest an emerging healthcare disparity, with non-Hispanic Black boys of lower socioeconomic status undergoing more post-neonatal operative circumcisions that are more expensive and higher risk.


Assuntos
Circuncisão Masculina , Pré-Escolar , Estudos de Coortes , Procedimentos Cirúrgicos Eletivos , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
18.
Med Dosim ; 47(1): 70-78, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34696931

RESUMO

To compare stereotactic radiosurgery (SRS) plan quality metrics of manual forward planning (MFP) and Elekta Fast Inverse Planning™ (FIP)-based inversely optimized plans for patients treated with Gamma Knife®. Clinically treated, MFP SRS plans for 100 consecutive patients (115 lesions; 67 metastatic and 48 benign) were replanned with the FIP dose optimizer based on a convex linear programming formulation. Comparative plans were generated to match or exceed the following metrics in order of importance: Target Coverage (TC), Paddick Conformity Index (PCI), beam-on time (BOT), and Gradient Index (GI). Plan quality metrics and delivery parameters between MFP and FIP were compared for all lesions and stratified into subgroups for further analysis. Additionally, performance of FIP for multiple punctate (<4 mm) metastatic lesions on a subset of cases was investigated. A Wilcoxon signed-rank test for non-normal distributions was used to assess the statistical differences between the MFP and FIP treatment plans. Overall, 76% (87/115) of FIP plans showed a statistically significant improvement in plan quality compared to MFP plans. As compared to MFP, FIP plans demonstrated an increase in the median PCI by 1.1% (p<0.01), a decrease in GI by 3.7% (p< 0.01), and an increase in median number of shots by 74% (p< 0.01). TC and BOT were not statistically significantly different between MFP and FIP plans (p>0.05). FIP plans showed a statistically significant increase in use of 16 mm (p< 0.01) and blocked shots (p< 0.01), with a corresponding decrease in 4 mm shots (p< 0.01). Use of multiple shots per coordinate was significantly higher in FIP plans (p<0.01). The FIP optimizer failed to generate a clinically acceptable plan in 4/115 (3.5%) lesions despite optimization parameter changes. The mean optimization time for FIP plans was 5.0 min (Range: 1.0 - 10.0 min). In the setting of multiple punctate lesions, PCI for FIP was significantly improved (p<0.01) by changing the default low-dose/BOT penalty optimization setting from a default of 50/50 to 75-85/40. FIP offers a significant reduction in manual effort for SRS treatment planning while achieving comparable plan quality to an expert planner-substantially improving overall planning efficiency. FIP plans employ a non-intuitive increased use of blocked sectors and shot-in-shot technique to achieve high quality plans. Several FIP plans failed to achieve clinically acceptable treatments and warrant further investigation.


Assuntos
Neoplasias Encefálicas , Raio , Radiocirurgia , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
19.
Acad Pediatr ; 22(4): 614-621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34929386

RESUMO

OBJECTIVE: Reutilization following discharge is costly to families and the health care system. Singular measures of the social determinants of health (SDOH) have been shown to impact utilization; however, the SDOH are multifactorial. The Childhood Opportunity Index (COI) is a validated approach for comprehensive estimation of the SDOH. Using the COI, we aimed to describe the association between SDOH and 30-day revisit rates. METHODS: This retrospective study included children 0 to 17 years within 48 children's hospitals using the Pediatric Health Information System from 1/1/2019 to 12/31/2019. The main exposure was a child's ZIP code level COI. The primary outcome was unplanned readmissions and emergency department (ED) revisits within 30 days of discharge. Primary outcomes were summarized by COI category and compared using chi-square or Kruskal-Wallis tests. Adjusted analysis used generalized linear mixed effects models with adjustments for demographics, clinical characteristics, and hospital clustering. RESULTS: Of 728,997 hospitalizations meeting inclusion criteria, 30-day unplanned returns occurred for 96,007 children (13.2%). After adjustment, the patterns of returns were significantly associated with COI. For example, 30-day returns occurred for 19.1% (95% confidence interval [CI]: 18.2, 20.0) of children living within very low opportunity areas, with a gradient-like decrease as opportunity increased (15.5%, 95% CI: 14.5, 16.5 for very high). The relative decrease in utilization as COI increased was more pronounced for ED revisits. CONCLUSIONS: Children living in low opportunity areas had greater 30-day readmissions and ED revisits. Our results suggest that a broader approach, including policy and system-level change, is needed to effectively reduce readmissions and ED revisits.


Assuntos
Serviço Hospitalar de Emergência , Readmissão do Paciente , Criança , Hospitais Pediátricos , Humanos , Alta do Paciente , Estudos Retrospectivos
20.
Pediatrics ; 149(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34854922

RESUMO

BACKGROUND AND OBJECTIVES: Children with neurologic impairment (NI) are a growing subset of children who frequently use health care. We examined health care use and spending trends across services for children with NI during their first 5 years of life. METHODS: This was a retrospective study of 13 947 children with NI in the multistate IBM Medicaid MarketScan Database (2009-2017). We established birth cohorts of children with NI and analyzed claims from birth to 5 years. NI, identified by using International Classification of Diseases, 9th Revision, diagnosis codes, was defined as ≥1 neurologic diagnosis that was associated with functional and/or intellectual impairment. We measured annual health care use and per-member-per-year spending by inpatient, emergency department (ED), and outpatient services. Population trends in use and spending were assessed with logistic and linear regression, respectively. RESULTS: During their first versus fifth year, 66.8% vs 5.8% of children with NI used inpatient services, and 67.8% vs 44.4% used ED services. Annual use in both categories decreased over 0-5 years (inpatient odds ratio: 0.35, 95% confidence interval: 0.34 to 0.36; ED odds ratio: 0.78, 95% confidence interval: 0.77 to 0.79). The use of outpatient services (primary care, specialty care, home health) decreased gradually. Per-member-per-year spending on inpatient services remained the largest spending category: $83 352 (90.2% of annual spending) in the first year and $1944 (25.5%) in the fifth year. CONCLUSIONS: For children with early-onset NI from 0-5 years, use and spending on inpatient services decreased dramatically; ED and outpatient service use decreased more gradually. These findings may help systems, clinicians, and families optimize care by anticipating and adjusting for shifting use of health care services.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Doenças do Sistema Nervoso/terapia , Serviços de Saúde da Criança/estatística & dados numéricos , Pré-Escolar , Utilização de Instalações e Serviços , Feminino , Serviços de Assistência Domiciliar/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Medicaid , Serviços de Saúde Mental/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos
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