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1.
J Arthroplasty ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428687

RESUMO

BACKGROUND: Patient activity after total knee arthroplasty (TKA) surgery has been estimated through patient-reported outcome measures. The use of data from an implanted sensor that transmits daily gait activity provides a more objective, complete recovery trajectory. METHODS: In this retrospective analysis of 794 patients who received a TKA with sensors in the tibial extension between October 4, 2021, and January 13, 2023, the average age of the patients was 64 years, and the cohort was 54.9% women. During the 6-week postoperative period, 90.3% of patients transmitted data. Patient activity in terms of qualified step count, cadence, walking speed, stride length, functional tibial range of motion (ROM), and functional knee ROM were compared at 1 week, 3 weeks, and 6 weeks postoperatively. RESULTS: All gait parameters increased in the first 6 weeks postsurgery: qualified step count increased 733%, cadence increased 22%, walking speed increased 50%, stride length increased 17%, tibial ROM increased 19%, and functional knee ROM increased 14%. There were statistically significant differences at both postoperative periods (P = .029, P < .001, and P < .001 at 3 and 6 weeks, respectively) in step counts for different body mass index (BMI) categories, with qualified step counts decreasing with increasing BMI. Patients under 65 years tended to have a higher qualified step count than those 65 and older at all time points, but these differences were not statistically significant. Men had significantly higher step counts than women (P < .001 at 1, 3, and 6 weeks). CONCLUSIONS: Initial results with an implanted sensor that collects data during activities of daily living confirm that 90% of patients transmit objective gait metrics daily after TKA surgery. Those results differ by sex and BMI. LEVEL OF EVIDENCE: III Retrospective Cohort Study.

2.
J Urban Health ; 100(4): 802-810, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37580543

RESUMO

A person's place of residence is a strong risk factor for important diagnosed chronic diseases such as diabetes. It is unclear whether neighborhood-level risk factors also predict the probability of undiagnosed disease. The objective of this study was to identify neighborhood-level variables associated with severe hyperglycemia among emergency department (ED) patients without a history of diabetes. We analyzed patients without previously diagnosed diabetes for whom a random serum glucose value was obtained in the ED. We defined random glucose values ≥ 200 mg/dL as severe hyperglycemia, indicating probable undiagnosed diabetes. Patient addresses were geocoded and matched with neighborhood-level socioeconomic measures from the American Community Survey and claims-based surveillance estimates of diabetes prevalence. Neighborhood-level exposure variables were standardized based on z-scores, and a series of logistic regression models were used to assess the association of selected exposures and hyperglycemia adjusting for biological and social individual-level risk factors for diabetes. Of 77,882 ED patients without a history of diabetes presenting in 2021, 1,715 (2.2%) had severe hyperglycemia. Many geospatial exposures were associated with uncontrolled hyperglycemia, even after controlling for individual-level risk factors. The most strongly associated neighborhood-level variables included lower markers of educational attainment, higher percentage of households where limited English is spoken, lower rates of white-collar employment, and higher rates of Medicaid insurance. Including these geospatial factors in risk assessment models may help identify important subgroups of patients with undiagnosed disease.


Assuntos
Diabetes Mellitus , Hiperglicemia , Doenças não Diagnosticadas , Humanos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/diagnóstico , Hiperglicemia/epidemiologia , Hiperglicemia/diagnóstico , Fatores de Risco , Serviço Hospitalar de Emergência , Características de Residência , Glucose
3.
Int J Health Geogr ; 22(1): 24, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730612

RESUMO

BACKGROUND: Communities in the United States (US) exist on a continuum of urbanicity, which may inform how individuals interact with their food environment, and thus modify the relationship between food access and dietary behaviors. OBJECTIVE: This cross-sectional study aims to examine the modifying effect of community type in the association between the relative availability of food outlets and dietary inflammation across the US. METHODS: Using baseline data from the REasons for Geographic and Racial Differences in Stroke study (2003-2007), we calculated participants' dietary inflammation score (DIS). Higher DIS indicates greater pro-inflammatory exposure. We defined our exposures as the relative availability of supermarkets and fast-food restaurants (percentage of food outlet type out of all food stores or restaurants, respectively) using street-network buffers around the population-weighted centroid of each participant's census tract. We used 1-, 2-, 6-, and 10-mile (~ 2-, 3-, 10-, and 16 km) buffer sizes for higher density urban, lower density urban, suburban/small town, and rural community types, respectively. Using generalized estimating equations, we estimated the association between relative food outlet availability and DIS, controlling for individual and neighborhood socio-demographics and total food outlets. The percentage of supermarkets and fast-food restaurants were modeled together. RESULTS: Participants (n = 20,322) were distributed across all community types: higher density urban (16.7%), lower density urban (39.8%), suburban/small town (19.3%), and rural (24.2%). Across all community types, mean DIS was - 0.004 (SD = 2.5; min = - 14.2, max = 9.9). DIS was associated with relative availability of fast-food restaurants, but not supermarkets. Association between fast-food restaurants and DIS varied by community type (P for interaction = 0.02). Increases in the relative availability of fast-food restaurants were associated with higher DIS in suburban/small towns and lower density urban areas (p-values < 0.01); no significant associations were present in higher density urban or rural areas. CONCLUSIONS: The relative availability of fast-food restaurants was associated with higher DIS among participants residing in suburban/small town and lower density urban community types, suggesting that these communities might benefit most from interventions and policies that either promote restaurant diversity or expand healthier food options.


Assuntos
Dieta , Inflamação , Humanos , Estudos Transversais , Inflamação/diagnóstico , Inflamação/epidemiologia , Restaurantes , População Rural
4.
BMC Health Serv Res ; 23(1): 41, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647113

RESUMO

BACKGROUND: While emerging studies suggest that the COVID-19 pandemic caused disruptions in routine healthcare utilization, the full impact of the pandemic on healthcare utilization among diverse group of patients with type 2 diabetes is unclear. The purpose of this study is to examine trends in healthcare utilization, including in-person and telehealth visits, among U.S. veterans with type 2 diabetes before, during and after the onset of the COVID-19 pandemic, by demographics, pre-pandemic glycemic control, and geographic region. METHODS: We longitudinally examined healthcare utilization in a large national cohort of veterans with new diabetes diagnoses between January 1, 2008 and December 31, 2018. The analytic sample was 733,006 veterans with recently-diagnosed diabetes, at least 1 encounter with veterans administration between March 2018-2020, and followed through March 2021. Monthly rates of glycohemoglobin (HbA1c) measurements, in-person and telehealth outpatient visits, and prescription fills for diabetes and hypertension medications were compared before and after March 2020 using interrupted time-series design. Log-linear regression model was used for statistical analysis. Secular trends were modeled with penalized cubic splines. RESULTS: In the initial 3 months after the pandemic onset, we observed large reductions in monthly rates of HbA1c measurements, from 130 (95%CI,110-140) to 50 (95%CI,30-80) per 1000 veterans, and in-person outpatient visits, from 1830 (95%CI,1640-2040) to 810 (95%CI,710-930) per 1000 veterans. However, monthly rates of telehealth visits doubled between March 2020-2021 from 330 (95%CI,310-350) to 770 (95%CI,720-820) per 1000 veterans. This pattern of increases in telehealth utilization varied by community type, with lowest increase in rural areas, and by race/ethnicity, with highest increase among non-hispanic Black veterans. Combined in-person and telehealth outpatient visits rebounded to pre-pandemic levels after 3 months. Despite notable changes in HbA1c measurements and visits during that initial window, we observed no changes in prescription fills rates. CONCLUSIONS: Healthcare utilization among veterans with diabetes was substantially disrupted at the onset of the pandemic, but rebounded after 3 months. There was disparity in uptake of telehealth visits by geography and race/ethnicity.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Disparidades em Assistência à Saúde , Telemedicina , Veteranos , Humanos , COVID-19/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde
5.
J Urban Health ; 99(3): 482-491, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35641714

RESUMO

Infants born with low or high ("at-risk") birthweights are at greater risk of adverse health outcomes across the life course. Our objective was to examine whether geographic hotspots of low and high birthweight prevalence in New York City had different patterns of neighborhood risk factors. We performed census tract-level geospatial clustering analyses using (1) birthweight prevalence and maternal residential address from an all-payer claims database and (2) domains of neighborhood risk factors (socioeconomic and food environment) from national and local datasets. We then used logistic regression analysis to identify specific neighborhood risk factors associated with low and high birthweight hotspots. This study examined 2088 census tracts representing 419,025 infants. We found almost no overlap (1.5%) between low and high birthweight hotspots. The majority of low birthweight hotspots (87.2%) overlapped with a socioeconomic risk factor and 95.7% overlapped with a food environment risk factor. Half of high birthweight hotspots (50.0%) overlapped with a socioeconomic risk factor and 48.8% overlapped with a food environment risk factor. Low birthweight hotspots were associated with high prevalence of excessive housing cost, unemployment, and poor food environment. High birthweight hotspots were associated with high prevalence of uninsured persons and convenience stores. Programs and policies that aim to prevent disparities in infant birthweight should examine the broader context by which hotspots of at-risk birthweight overlap with neighborhood risk factors. Multi-level strategies that include the neighborhood context are needed to address prenatal pathways leading to low and high birthweight outcomes.


Assuntos
Recém-Nascido de Baixo Peso , Características de Residência , Peso ao Nascer , Feminino , Humanos , Lactente , Recém-Nascido , Cidade de Nova Iorque/epidemiologia , Gravidez , Fatores Socioeconômicos
6.
Undersea Hyperb Med ; 49(3): 295-305, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36001562

RESUMO

Introduction: Few treatments have demonstrated mortality benefits among hospitalized hypoxic COVID-19 patients. We evaluated the use of hyperbaric oxygen (HBO2) therapy as a therapeutic intervention among hospitalized patients with a high oxygen requirement prior to vaccine approval. Methods: We extracted data on patients with COVID-19 hypoxia who required oxygen supplementation ranging from a 6L nasal cannula up to a high-flow nasal cannula at 100% FiO2 at 60L/minute with a 100% non-rebreather mask at 15 L/minute and were eligible for off-label HBO2 therapy from October 2020 to February 2021. We followed the Monitored Emergency use of Unregistered and Investigational Interventions or (MEURI) in conjunction with the consistent re-evaluation of the protocol using the Plan-Do-Study-Act (PDSA) tool [1]. We compared patient characteristics and used Fisher's exact test and a survival analysis to assess the primary endpoint of inpatient death. Results: HBO2 therapy was offered to 36 patients, of which 24 received treatment and 12 did not receive treatment. Patients who did not receive treatment were significantly older (p ≺ 0.01) and had worse baseline hypoxia (p = 0.06). Three of the 24 (13%) patients who received treatment died compared to six of 12 (50%) patients who did not receive treatment (RR ratio: 0.25, p = 0.04, 95% CI: 0.08 to 0.83). In the survival analysis, there was a statistically significant reduction in inpatient mortality in the treatment group (HR: 0.19, p = 0.02, 95% CI: 0.05-0.74). However, after adjusting for age and baseline hypoxia, there was no difference in inpatient mortality (hazard ratio: 0.48, p = 0.42, 95% CI: 0.08-2.86). Conclusion: The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.


Assuntos
COVID-19 , Oxigenoterapia Hiperbárica , Vacinas , COVID-19/terapia , Humanos , Oxigenoterapia Hiperbárica/métodos , Hipóxia/etiologia , Hipóxia/terapia , Oxigênio/uso terapêutico , Resultado do Tratamento
7.
J Public Health Manag Pract ; 28(1): E109-E118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32487918

RESUMO

CONTEXT: Disease burden may vary substantively across neighborhoods in an urban setting. Yet, data available for monitoring chronic conditions at the neighborhood level are scarce. Large health care data sets have potential to complement population health surveillance. Few studies have examined the utility of health care data for neighborhood-level surveillance. OBJECTIVE: We examined the use of primary care electronic health records (EHRs) and emergency department (ED) claims for identifying neighborhoods with higher chronic disease burden and neighborhood-level prevalence estimation. DESIGN: Comparison of hypertension and diabetes estimates from EHRs and ED claims with survey-based estimates. SETTING: Forty-two United Hospital Fund neighborhoods in New York City. PARTICIPANTS: The EHR sample comprised 708 452 patients from the Hub Population Health System (the Hub) in 2015, and the ED claim sample comprised 1 567 870 patients from the Statewide Planning and Research Cooperative System in 2015. We derived survey-based estimates from 2012 to 2016 Community Health Survey (n = 44 189). MAIN OUTCOME MEASURE: We calculated hypertension and diabetes prevalence estimates by neighborhood from each data source. We obtained Pearson correlation and absolute difference between EHR-based or claims-based estimates and survey-based estimates. RESULTS: Both EHR-based and claims-based estimates correlated strongly with survey-based estimates for hypertension (0.91 and 0.72, respectively) and diabetes (0.83 and 0.82, respectively) and identified similar neighborhoods of higher burden. For hypertension, 10 and 17 neighborhoods from the EHRs and ED claims, respectively, had an absolute difference of more than 5 percentage points from the survey-based estimate. For diabetes, 15 and 4 neighborhoods from the EHRs and ED claims, respectively, differed from the survey-based estimate by more than 5 percentage points. CONCLUSIONS: Both EHRs and ED claims data are useful for identifying neighborhoods with greater disease burden and have potential for monitoring chronic conditions at the neighborhood level.


Assuntos
Indicadores de Doenças Crônicas , Registros Eletrônicos de Saúde , Serviço Hospitalar de Emergência , Humanos , Atenção Primária à Saúde , Características de Residência
8.
Liver Transpl ; 27(3): 341-348, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33098253

RESUMO

Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual-energy X-ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual-energy abdominal triple-phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA-based osteoporosis was defined as a T score ≤-2.5 at the hip or spine. BCT-based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3 . Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2 . Using DXA as the clinical reference, sensitivity of BCT to detect DXA-defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple-phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.


Assuntos
Transplante de Fígado , Osteoporose , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Estudos Retrospectivos
9.
Emerg Themes Epidemiol ; 17(1): 3, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33292290

RESUMO

BACKGROUND: Worsening socioeconomic conditions in rural America have been fueling increases in chronic disease and poor health. The goal of this study was to identify cost-effective methods of deploying geographically targeted health surveys in rural areas, which often have limited resources. These health surveys were administered in New York's rural Sullivan County, which has some of the poorest health outcomes in the entire state. METHODS: Comparisons were made for response rates, estimated costs, respondent demographics, and prevalence estimates of a brief health survey delivered by mail and phone using address-based sampling, and in-person using convenience sampling at a sub-county level in New York's rural Sullivan County during 2017. RESULTS: Overall response rates were 27.0% by mail, 8.2% by phone, and 71.4% for convenience in-person surveys. Costs to perform phone surveys were substantially higher than mailed or convenience in-person surveys. All modalities had lower proportions of Hispanic respondents compared to Census estimates. Unadjusted and age-adjusted prevalence estimates were similar between mailed and in-person surveys, but not for phone surveys. CONCLUSIONS: These findings are consistent with declining response rates of phone surveys, which obtained an inadequate sample of rural residents. Though in-person surveys had higher response rates, convenience sampling failed to obtain a geographically distributed sample of rural residents. Of modalities tested, mailed surveys provided the best opportunity to perform geographically targeted rural health surveillance.

10.
J Emerg Med ; 59(4): 610-618, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32737005

RESUMO

BACKGROUND: The coronavirus disease (COVID)-19 pandemic quickly challenged New York City health care systems. Telemedicine has been suggested to manage acute complaints and divert patients from in-person care. OBJECTIVES: The objective of this study was to describe and assess the impact of a rapidly scaled virtual urgent care platform during the COVID-19 pandemic. METHODS: This was a retrospective cohort study of all patients who presented to a virtual urgent care platform over 1 month during the COVID-19 pandemic surge. We described scaling our telemedicine urgent care capacity, described patient clinical characteristics, assessed for emergency department (ED) referrals, and analyzed postvisit surveys. RESULTS: During the study period, a total of 17,730 patients were seen via virtual urgent care; 454 (2.56%) were referred to an ED. The most frequent diagnoses were COVID-19 related or upper respiratory symptoms. Geospatial analysis indicated a wide catchment area. There were 251 providers onboarded to the platform; at peak, 62 providers supplied 364 h of coverage in 1 day. The average patient satisfaction score was 4.4/5. There were 2668 patients (15.05%) who responded to the postvisit survey; 1236 (49.35%) would have sought care in an ED (11.86%) or in-person urgent care (37.49%). CONCLUSIONS: A virtual urgent care platform was scaled to manage a volume of more than 800 patients a day across a large catchment area during the pandemic surge. About half of the patients would otherwise have presented to an ED or urgent care in person. Virtual urgent care is an option for appropriate patients while minimizing in-person visits during the COVID-19 pandemic.


Assuntos
Assistência Ambulatorial/métodos , COVID-19/epidemiologia , Telemedicina , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Pandemias , Satisfação do Paciente , Estudos Retrospectivos , SARS-CoV-2
11.
Undersea Hyperb Med ; 47(3): 405-413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32931666

RESUMO

Objective: Given the high mortality and prolonged duration of mechanical ventilation of COVID-19 patients, we evaluated the safety and efficacy of hyperbaric oxygen for COVID-19 patients with respiratory distress. Methods: This is a single-center clinical trial of COVID-19 patients at NYU Winthrop Hospital from March 31 to April 28, 2020. Patients in this trial received hyperbaric oxygen therapy at 2.0 atmospheres of pressure in monoplace hyperbaric chambers for 90 minutes daily for a maximum of five total treatments. Controls were identified using propensity score matching among COVID-19 patients admitted during the same time period. Using competing-risks survival regression, we analyzed our primary outcome of inpatient mortality and secondary outcome of mechanical ventilation. Results: We treated 20 COVID-19 patients with hyperbaric oxygen. Ages ranged from 30 to 79 years with an oxygen requirement ranging from 2 to 15 liters on hospital days 0 to 14. Of these 20 patients, two (10%) were intubated and died, and none remain hospitalized. Among 60 propensity-matched controls based on age, sex, body mass index, coronary artery disease, troponin, D-dimer, hospital day, and oxygen requirement, 18 (30%) were intubated, 13 (22%) have died, and three (5%) remain hospitalized (with one still requiring mechanical ventilation). Assuming no further deaths among controls, we estimate that the adjusted subdistribution hazard ratios were 0.37 for inpatient mortality (p=0.14) and 0.26 for mechanical ventilation (p=0.046). Conclusion: Though limited by its study design, our results demonstrate the safety of hyperbaric oxygen among COVID-19 patients and strongly suggests the need for a well-designed, multicenter randomized control trial.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Oxigenoterapia Hiperbárica/métodos , Pneumonia Viral/terapia , Pontuação de Propensão , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , Pressão Atmosférica , COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Oxigenoterapia Hiperbárica/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Respiração Artificial/mortalidade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Fatores de Risco , SARS-CoV-2 , Segurança , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
12.
J Proteome Res ; 18(9): 3369-3382, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31408348

RESUMO

Lung cancer is the most common cause of cancer-related mortality worldwide, characterized by late clinical presentation (49-53% of patients are diagnosed at stage IV) and consequently poor outcomes. One challenge in identifying biomarkers of early disease is the collection of samples from patients prior to symptomatic presentation. We used blood collected during surgical resection of lung tumors in an iTRAQ isobaric tagging experiment to identify proteins effluxing from tumors into pulmonary veins. Forty proteins were identified as having an increased abundance in the vein draining from the tumor compared to "healthy" pulmonary veins. These protein markers were then assessed in a second cohort that utilized the mass spectrometry (MS) technique: Sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS. SWATH-MS was used to measure proteins in serum samples taken from 25 patients <50 months prior to and at lung cancer diagnosis and 25 matched controls. The SWATH-MS analysis alone produced an 11 protein marker panel. A machine learning classification model was generated that could discriminate patient samples from patients within 12 months of lung cancer diagnosis and control samples. The model was evaluated as having a mean AUC of 0.89, with an accuracy of 0.89. This panel was combined with the SWATH-MS data from one of the markers from the first cohort to create a 12 protein panel. The proteome signature developed for lung cancer risk can now be developed on further cohorts.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/sangue , Proteômica , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteoma/genética , Espectrometria de Massas em Tandem/métodos
13.
Mol Pharmacol ; 96(4): 475-484, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31399497

RESUMO

Topoisomerase II (TOP2) poisons are effective cytotoxic anticancer agents that stabilize the normally transient TOP2-DNA covalent complexes formed during the enzyme reaction cycle. These drugs include etoposide, mitoxantrone, and the anthracyclines doxorubicin and epirubicin. Anthracyclines also exert cell-killing activity via TOP2-independent mechanisms, including DNA adduct formation, redox activity, and lipid peroxidation. Here, we show that anthracyclines and another intercalating TOP2 poison, mitoxantrone, stabilize TOP2-DNA covalent complexes less efficiently than etoposide, and at higher concentrations they suppress the formation of TOP2-DNA covalent complexes, thus behaving as TOP2 poisons at low concentration and inhibitors at high concentration. We used induced pluripotent stem cell (iPSC)-derived human cardiomyocytes as a model to study anthracycline-induced damage in cardiac cells. Using immunofluorescence, our study is the first to demonstrate the presence of topoisomerase IIß (TOP2B) as the only TOP2 isoform in iPSC-derived cardiomyocytes. In these cells, etoposide robustly induced TOP2B covalent complexes, but we could not detect doxorubicin-induced TOP2-DNA complexes, and doxorubicin suppressed etoposide-induced TOP2-DNA complexes. In vitro, etoposide-stabilized DNA cleavage was attenuated by doxorubicin, epirubicin, or mitoxantrone. Clinical use of anthracyclines is associated with cardiotoxicity. The observations in this study have potentially important clinical consequences regarding the effectiveness of anticancer treatment regimens when TOP2-targeting drugs are used in combination. These observations suggest that inhibition of TOP2B activity, rather than DNA damage resulting from TOP2 poisoning, may play a role in doxorubicin cardiotoxicity. SIGNIFICANCE STATEMENT: We show that anthracyclines and mitoxantrone act as topoisomerase II (TOP2) poisons at low concentration but attenuate TOP2 activity at higher concentration, both in cells and in in vitro cleavage experiments. Inhibition of type II topoisomerases suppresses the action of other drugs that poison TOP2. Thus, combinations containing anthracyclines or mitoxantrone and etoposide may reduce the activity of etoposide as a TOP2 poison and thus reduce the efficacy of drug combinations.


Assuntos
Antraciclinas/farmacologia , Adutos de DNA/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Etoposídeo/farmacologia , Mitoxantrona/farmacologia , Cardiotoxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Adutos de DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células K562 , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Inibidores da Topoisomerase II/farmacologia
14.
Prev Chronic Dis ; 16: E101, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370917

RESUMO

INTRODUCTION: Although screening for diabetes is recommended at age 45, some populations may be at greater risk at earlier ages. Our objective was to quantify age disparities among patients with type 2 diabetes in New York City. METHODS: Using all-payer hospital claims data for New York City, we performed a cross-sectional analysis of patients with type 2 diabetes identified from emergency department visits during the 5-year period 2011-2015. We estimated type 2 diabetes prevalence at each year of life, the age distribution of patients stratified by decade, and the average age of patients by sex, race/ethnicity, and geographic location. RESULTS: We identified 576,306 unique patients with type 2 diabetes. These patients represented more than half of all people with type 2 diabetes in New York City. Patients in racial/ethnic minority groups were on average 5.5 to 8.4 years younger than non-Hispanic white patients. At age 45, type 2 diabetes prevalence was 10.9% among non-Hispanic black patients and 5.2% among non-Hispanic white patients. In our geospatial analyses, patients with type 2 diabetes were on average 6 years younger in hotspots of diabetes-related emergency department use and inpatient hospitalizations. The average age of patients with type 2 diabetes was also 1 to 2 years younger in hotspots of microvascular diabetic complications. CONCLUSION: We identified profound age disparities among patients with type 2 diabetes in racial/ethnic minority groups and in neighborhoods with poor health outcomes. The younger age of these patients may be due to earlier onset of diabetes and/or earlier death from diabetic complications. Our findings demonstrate the need for geographically targeted interventions that promote earlier diagnosis and better glycemic control.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Idade de Início , Estudos Transversais , Complicações do Diabetes/etnologia , Complicações do Diabetes/prevenção & controle , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diagnóstico Precoce , Feminino , Disparidades nos Níveis de Saúde , Hispânico ou Latino/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Cidade de Nova Iorque/epidemiologia , Prevalência
15.
Foot Ankle Surg ; 24(6): 530-534, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29409268

RESUMO

BACKGROUND: Bunionette deformity is a painful bony prominence of the 5th metatarsal. We evaluated outcomes of using a Kramer osteotomy to treat this condition. METHODS: Retrospective study of patients treated with a Kramer osteotomy from 2003 and 2016. Outcome measures included Foot Functional Index (FFI) and radiographic measurements. RESULTS: 38 patients (43 feet) with an average follow-up of 55 months. Mean postoperative FFI1 was 19.4. Mean 4-5 IMA2 improved 3.9°, from 8.3° preoperatively to 4.4° on final postoperative films (p<0.01). Mean MTP-53 angle improved 13.2° from 13.6° preoperatively to 0.4° at final follow-up (p<0.01). There were 5 delayed unions (11.6%) and 1 non-union (2.3%). CONCLUSIONS: The Kramer osteotomy is an effective treatment option in patients with bunionette deformity, with significant correction of the 4-5 IM2 and MTP-53 angles and few complications.


Assuntos
Joanete do Alfaiate/diagnóstico por imagem , Joanete do Alfaiate/cirurgia , Osteotomia/métodos , Feminino , Humanos , Masculino , Ossos do Metatarso/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
16.
Am J Geriatr Psychiatry ; 25(9): 953-963, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28506605

RESUMO

OBJECTIVE: To characterize risk factors for and consequences of post-traumatic stress disorder (PTSD) among older adults evaluated in the emergency department (ED) following motor vehicle collision (MVC). DESIGN: Prospective multicenter longitudinal study (2011-2015). SETTING: 9 EDs across the United States. PARTICIPANTS: Adults aged 65 years and older who presented to an ED after MVC without severe injuries. MEASUREMENTS: PTSD symptoms were assessed 6 months after the ED visit using the Impact of Event Scale-Revised. RESULTS: Of 223 patients, clinically significant PTSD symptoms at 6 months were observed in 21% (95% CI 16%-26%). PTSD symptoms were more common in patients who did not have a college degree, had depressive symptoms prior to the MVC, perceived the MVC as life-threatening, had severe ED pain, and expected their physical or emotional recovery time to be greater than 30 days. Three factors (ED pain severity [0-10 scale], perceived life-threatening MVC [0-10 scale], and pre-MVC depressive symptoms [yes to either of two questions]), predicted 6-month PTSD symptoms with an area under the curve of 0.76. Compared to patients without PTSD symptoms, those with PTSD symptoms were at higher risk for persistent pain (72% versus 30%), functional decline (67% versus 42%), and new disability (49% versus 18%). CONCLUSIONS: Among older adults treated in the ED following MVC, clinically significant PTSD symptoms at 6 months were present in 21% of patients and were associated with adverse health outcomes. Increased risk for PTSD development can be identified with moderate accuracy using information readily available in the ED.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Envelhecimento , Atitude Frente a Saúde , Depressão/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Dor/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Acidentes de Trânsito/psicologia , Idoso , Envelhecimento/psicologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Dor/etiologia , Dor/psicologia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia
17.
Radiology ; 278(1): 172-80, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26200602

RESUMO

PURPOSE: To evaluate the ability of additional analysis of computed tomographic (CT) colonography images to provide a comprehensive osteoporosis assessment. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant study was approved by our institutional review board with a waiver of informed consent. Diagnosis of osteoporosis and assessment of fracture risk were compared between biomechanical CT analysis and dual-energy x-ray absorptiometry (DXA) in 136 women (age range, 43-92 years), each of whom underwent CT colonography and DXA within a 6-month period (between January 2008 and April 2010). Blinded to the DXA data, biomechanical CT analysis was retrospectively applied to CT images by using phantomless calibration and finite element analysis to measure bone mineral density and bone strength at the hip and spine. Regression, Bland-Altman, and reclassification analyses and paired t tests were used to compare results. RESULTS: For bone mineral density T scores at the femoral neck, biomechanical CT analysis was highly correlated (R(2) = 0.84) with DXA, did not differ from DXA (P = .15, paired t test), and was able to identify osteoporosis (as defined by DXA), with 100% sensitivity in eight of eight patients (95% confidence interval [CI]: 67.6%, 100%) and 98.4% specificity in 126 of 128 patients (95% CI: 94.5%, 99.6%). Considering both the hip and spine, the classification of patients at high risk for fracture by biomechanical CT analysis--those with osteoporosis or "fragile bone strength"--agreed well against classifications for clinical osteoporosis by DXA (T score ≤-2.5 at the hip or spine), with 82.8% sensitivity in 24 of 29 patients (95% CI: 65.4%, 92.4%) and 85.7% specificity in 66 of 77 patients (95% CI: 76.2%, 91.8%). CONCLUSION: Retrospective biomechanical CT analysis of CT colonography for colorectal cancer screening provides a comprehensive osteoporosis assessment without requiring changes in imaging protocols.


Assuntos
Colonografia Tomográfica Computadorizada/métodos , Colo do Fêmur/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Densidade Óssea , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Psychosom Med ; 78(1): 68-78, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26588823

RESUMO

OBJECTIVES: To determine the influence of epidemiologic factors and the influence of genetic variants affecting FKBP5, a protein known to modulate hypothalamic-pituitary-adrenocortical axis function, on the severity of somatic symptoms commonly termed "postconcussive" 6 and 12 months after motor vehicle collision (MVC). METHODS: European Americans 18 to 65 years of age who presented to one of eight emergency departments (EDs) after MVC were enrolled. Exclusion criteria included hospital admission. Blood samples were collected in the ED for genotyping. Participants completed evaluations including an adapted Rivermead Post-Concussive Symptoms Questionnaire in the ED and at 6 weeks, 6 months, and 1 year. Repeated-measures analysis of covariance was used to evaluate the association between epidemiologic factors (sociodemographic, pre-MVC health, collision characteristics, head injury, peritraumatic pain, and stress), FKBP5 genetic variants, and postconcussive symptom severity. RESULTS: Among 943 patients recruited in the ED, follow-up was completed on 835 (88%) at 6 months and 857 (90%) at 1 year. Self-reported head impact during collision was not associated with chronic postconcussive symptom severity. After correction for multiple testing, three FKBP5 single-nucleotide polymorphisms (rs3800373, rs7753746, and rs9380526) predicted chronic postconcussive symptom severity, with an average symptom severity of 1.10 (95% confidence interval = 0.96-1.24), 1.36 (1.21-1.51), and 1.55 (1.23-1.88) for one, two, or three copies of minor allele at rs3800373 (p = .001). Similar effect sizes were observed for the minor alleles of rs7753746 and rs9380526. CONCLUSIONS: Postconcussive symptoms after minor MVC are not generally related to the severity of mild brain injury. This study shows that neurobiologic stress systems may play a role in the pathogenesis of postconcussive symptoms.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Polimorfismo de Nucleotídeo Único , Síndrome Pós-Concussão/genética , Proteínas de Ligação a Tacrolimo/genética , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Serviço Hospitalar de Emergência , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Síndrome Pós-Concussão/epidemiologia , Síndrome Pós-Concussão/fisiopatologia , Síndrome Pós-Concussão/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Proteínas de Ligação a Tacrolimo/sangue , Adulto Jovem
20.
Ann Emerg Med ; 67(2): 166-176.e1, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26092559

RESUMO

STUDY OBJECTIVE: Motor vehicle crashes are the second most common form of trauma among older adults. We seek to describe the incidence, risk factors, and consequences of persistent pain among older adults evaluated in the emergency department (ED) after a motor vehicle crash. METHODS: We conducted a prospective longitudinal study of patients aged 65 years or older who presented to one of 8 EDs after motor vehicle crash between June 2011 and June 2014 and were discharged home after evaluation. ED evaluation was done through in-person interview; follow-up data were obtained through mail-in survey or telephone call. Pain severity (0 to 10 scale) overall and for 15 parts of the body were assessed at each follow-up point. Principal component analysis was used to assess the dimensionality of the locations of pain data. Participants reporting pain severity greater than or equal to 4 attributed to the motor vehicle crash at 6 months were defined as having persistent pain. RESULTS: Of the 161 participants, 72% reported moderate to severe pain at the ED evaluation. At 6 months, 26% of participants reported moderate to severe motor vehicle crash-related pain. ED characteristics associated with persistent pain included acute pain severity; pain located in the head, neck, and jaw or lower back and legs; poor self-rated health; less formal education; pre-motor vehicle crash depressive symptoms; and patient's expected time to physical recovery more than 30 days. Compared with individuals without persistent pain, those with persistent pain were substantially more likely at 6-month follow-up to have also experienced a decline in their capacity for physical function (73% versus 36%; difference=37%; 95% confidence interval [CI] 19% to 52%), a new difficulty with activities of daily living (42% versus 17%; difference=26%; 95% CI 10% to 43%), a 1-point or more reduction in overall self-rated health on a 5-point scale (54% versus 30%; difference=24%; 95% CI 6% to 41%), and a change in their living situation to obtain additional help (23% versus 8%; difference=15%; 95% CI 2% to 31%). CONCLUSION: Among older adults discharged home from the ED post-evaluation after a motor vehicle crash, persistent pain is common and frequently associated with functional decline and disability.


Assuntos
Acidentes de Trânsito , Dor/epidemiologia , Dor/etiologia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Serviço Hospitalar de Emergência , Feminino , Avaliação Geriátrica , Humanos , Incidência , Escala de Gravidade do Ferimento , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Medição da Dor , Alta do Paciente , Estudos Prospectivos , Fatores de Risco
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