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1.
Res Q Exerc Sport ; : 1-13, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990545

RESUMEN

Purpose: Youth sport (YS) is a community system for promoting children's physical activity (PA). Studies have examined mean PA during YS practices, but few have examined inequalities in the distribution of PA among children during practice time. This study examined PA inequality in time-segmented YS practices and differences in inequality by time segment characteristics. Methods: Children's PA and YS practices were examined using accelerometer and video observation data from a sample of YS teams (n = 36 teams, n = 101 practices) for third- through sixth-grade children (n = 392), approximately eight to 12 years old, in two rural U.S. communities. Practices were time-segmented into smaller units (episodes; n = 991). Episodes were assigned codes for purpose (e.g. warm-up), member arrangement (e.g. whole group), and setting demand (i.e. fosters participation, creates exclusion). Group accelerometer data were paired with episodes, and the Gini coefficient quantified inequality in activity counts and minutes of moderate-to-vigorous PA (MVPA). Beta generalized estimating equations examined the influence of episode structure on PA inequality. Results: Warm-up (Gini = 0.22), fitness (Gini = 0.24), and sport skill (Gini = 0.24) episodes had significantly lower inequality (p < .05) in activity counts than other purpose types. Management (Gini = 0.32) and strategy (Gini = 0.40) episodes had significantly greater inequality (p < .05) in MVPA minutes than other purpose types. Episodes fostering participation (Gini = 0.32) had significantly lower activity count inequality (p < .05) than episodes creating exclusion (Gini = 0.35). Conclusion: PA inequality among children during YS varied by practice structure. Metrics such as the Gini coefficient can illuminate inequalities in PA and may be useful for guiding efforts to improve population PA in children. Trial Registration: This study is registered at www.clinicaltrials.gov (Identifier: NCT03380143).

2.
Phys Ther Sport ; 65: 102-106, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38103357

RESUMEN

BACKGROUND: Psychological response is important in return-to-sport decisions for athletes recovering from anterior cruciate ligament reconstruction (ACLR). The purpose of this study was to compare psychological response after ACLR with a concomitant meniscus repair compared to isolated ACLR. METHODS: Thirty-five individuals completed the Tampa Scale of Kinesiophobia (TSK) and Anterior Cruciate Ligament Return-to-Sport after Injury (ACL-RSI) scale before ACLR and 2, 4, and 6 months after ACLR. Participants were dichotomized based on presence of concomitant meniscus repair (Yes/No). Separate group X time repeated measures analyses of variance were conducted for both scales. RESULTS: Participants were 65.7% female, 19.1 ± 4.7 years old with BMI of 24.9 ± 4.4 kg/m2. Sixteen individuals had an isolated ACLR with 19 individuals having an ACLR with concomitant meniscus repair. For the TSK, there was a group × time interaction effect(p = 0.028), with improvement in TSK scores for the isolated ACLR group (ACLR:2 months = 24.8 ± 3.7; 4 months = 22.0 ± 5.7; 6 months: 19.9 ± 5.9; Meniscus Repair:2 months = 25.5 ± 4.7; 4 months = 24.1 ± 5.0; 6 months: 23.8 ± 4.7). Six months after ACLR, TSK scores were worse in the meniscus repair group(p = 0.036). For the ACL-RSI, there was no interaction(p = 0.07). CONCLUSION: Concomitant meniscus repair with ACLR results in less post-operative improvement in kinesiophobia through 6 months after ACLR compared to isolated ACLR.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Menisco , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Masculino , Kinesiofobia , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/psicología , Ligamento Cruzado Anterior/cirugía , Volver al Deporte/psicología , Reconstrucción del Ligamento Cruzado Anterior/psicología , Menisco/cirugía
3.
Respir Res ; 23(1): 247, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36114505

RESUMEN

BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. METHODS: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation. RESULTS: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22-0.57, Padj < 0.0001). CONCLUSIONS: Smoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Uteroglobina , Antiinflamatorios/metabolismo , Antioxidantes/metabolismo , Broncodilatadores/metabolismo , Estudios Transversales , Femenino , Humanos , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Humo , Fumar/efectos adversos , Fumar/epidemiología , Nicotiana , Uteroglobina/metabolismo
4.
Geohealth ; 6(2): e2021GH000419, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35372745

RESUMEN

This study was conducted to examine, at the county level, the relationship between pediatric cancer incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in groundwater. The age-adjusted brain and other CNS cancer incidence was higher than the national average in 63% of the Nebraska counties. After controlling for the counties socio-economic status and nitrate concentrations in groundwater, counties with groundwater atrazine concentrations above 0.0002 µg/L had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with groundwater atrazine concentrations in the reference group (0.0000-0.0002 µg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR = 8.39; 95% CI: 8.24-8.54), leukemia (IRR = 7.35; 95% CI: 7.22-7.48), and lymphoma (IRR = 5.59; CI: 5.48-5.69) after adjusting for atrazine groundwater concentration and the county socio-economic status. While these findings do not indicate a causal relationship, because other contaminants or cancer risk factors have not been accounted for, they suggest that atrazine and nitrate may pose a risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma.

5.
J Clin Neurophysiol ; 39(1): 85-91, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32604191

RESUMEN

PURPOSE: Prefabricated arrays with a limited number of electrodes offer an opportunity to hasten the diagnosis of seizures; however, their accuracy to detect seizures is unknown. We examined the utility of two limited-montage EEG setups for the detection of nonconvulsive seizures. METHODS: Thirty previously interpreted EEG segments with nonconvulsive seizures from 30 patients and 60 segments with background slowing or normal EEG from 60 patients were rendered in a bipolar "double banana" montage, a double distance "neonatal" montage, and a circumferential "hatband" montage. Experts reviewed 60 to 180 seconds long segments to determine whether seizures were present and if the EEG data provided were sufficient to make a decision on escalation of clinical care by ordering an additional EEG or prescribing anticonvulsants. The periodic patterns on the ictal-interictal continuum were specifically excluded for this analysis to keep the focus on definite electrographic seizures. RESULTS: The sensitivities for seizure of the neonatal and hatband montages were 0.96 and 0.84, respectively, when compared with full montage EEG, whereas the specificities were 0.94 and 0.98, respectively. Appropriate escalation of care was suggested for 96% and 92% of occurrences of seizure patterns in neonatal and hatband montages, respectively. When compared with clinical EEG, the sensitivities of the neonatal and hatband montages for seizure diagnosis were 0.85 and 0.69, respectively. CONCLUSIONS: Nonconvulsive seizures were detected with high accuracy using the limited electrode array configuration in the neonatal and hatband montages. The sensitivity of the neonatal montage EEG in detecting seizures was superior to that of a hatband montage. These findings suggest that in some patients with nonconvulsive seizures, limited-montage EEG may allow to differentiate ictal and slow patterns.


Asunto(s)
Electroencefalografía , Convulsiones , Electrodos , Humanos , Recién Nacido , Convulsiones/diagnóstico
6.
Int J STD AIDS ; 33(1): 38-47, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34565257

RESUMEN

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12 years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92-2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91-1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.


Asunto(s)
Trastorno Depresivo Mayor , Infecciones por VIH , Actividades Cotidianas , Terapia Antirretroviral Altamente Activa , Trastorno Depresivo Mayor/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Pruebas Neuropsicológicas
7.
Future Oncol ; 18(3): 311-321, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34761681

RESUMEN

Background: We used the Therapy Preference Scale, a 30-item questionnaire, to determine cancer treatment preferences of adults with cancer. Methods: We used Wilcoxon's rank sum test and Fisher's exact test to compare the preferences of younger (<60 years) versus older adults (≥60 years). Results: While 56% of patients would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Oral instead of intravenous treatment (p = 0.003), shorter hospital stay (p = 0.03), preservation of cognitive function (p = 0.01) and avoidance of pain (p = 0.02) were more important to older patients compared with younger patients. Conclusion: Many patients prioritized maintenance of cognition, functional ability and quality of life; older patients valued oral treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.


Lay abstract Understanding the preferences of adults with cancer is important for physicians to develop personalized cancer treatment plans. We used a self-reported 30-item questionnaire, the Therapy Preference Scale, to help patients express their preferences with regard to safety, efficacy and other aspects of therapy. While 56% of the patients in our study would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Compared with younger patients, older patients preferred oral instead of intravenous treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.


Asunto(s)
Antineoplásicos/administración & dosificación , Dolor en Cáncer/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Prioridad del Paciente/estadística & datos numéricos , Administración Intravenosa , Administración Oral , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Dolor en Cáncer/etiología , Dolor en Cáncer/psicología , Cognición/efectos de los fármacos , Toma de Decisiones , Humanos , Esperanza de Vida , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/psicología , Prioridad del Paciente/psicología , Calidad de Vida , Encuestas y Cuestionarios/estadística & datos numéricos , Adulto Joven
8.
PLoS One ; 16(4): e0248802, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33793575

RESUMEN

The association between HIV-associated neurocognitive impairment (NCI) and health-related quality of life (HRQoL) is not well known. We investigated this association among the CNS (Central Nervous System) HIV Antiretroviral Therapy Effects Research (CHARTER) study participants. We performed factor analysis to distinguish physical and mental HRQoL, followed by general linear models. We analyzed 1,340 HIV participants, including 35.6% with NCI, 77.2% males, 70.5% unemployed, and 42.2% with depression. Impaired participants had lower (worse) mental and physical HRQoL mean scores compared to unimpaired participants. NCI was negatively associated with mental HRQoL in crude (mean difference: -4.38; 95% CI: -6.70 to -2.06) and adjusted analysis (-2.56, -4.83 to -0.30). NCI was also negatively associated with physical HRQoL in unadjusted analysis (-4.62, -7.45 to -1.78), though the association weakened in the adjusted analysis (-2.20, -4.81 to 0.40). The association between NCI and HRQoL was confounded mainly by employment and was partially mediated by depression. These findings suggest that future strategies aimed at improving HRQoL among HIV-infected patients with NCI might benefit from concurrent management of depression.


Asunto(s)
Depresión/patología , Infecciones por VIH/complicaciones , VIH-1/patogenicidad , Trastornos Neurocognitivos/patología , Adulto , Depresión/etiología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Trastornos Neurocognitivos/etiología , Estudios Prospectivos , Calidad de Vida , Desempleo , Estados Unidos/epidemiología
9.
Sci Rep ; 11(1): 3738, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33580123

RESUMEN

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium's (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64-0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56-0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.


Asunto(s)
Disfunción Cognitiva/mortalidad , Disfunción Cognitiva/fisiopatología , Infecciones por VIH/mortalidad , Adulto , Antirretrovirales/uso terapéutico , Cognición/fisiología , Disfunción Cognitiva/virología , Estudios de Cohortes , Bases de Datos Factuales , Función Ejecutiva/fisiología , Femenino , VIH/metabolismo , VIH/patogenicidad , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Trastornos Neurocognitivos/mortalidad , Trastornos Neurocognitivos/fisiopatología , Trastornos Neurocognitivos/virología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología
10.
Future Oncol ; 17(1): 37-44, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33463372

RESUMEN

We incorporated questions related to safety, effectiveness and other characteristics of systemic cancer treatment into a self-report questionnaire - the Therapy Preference Scale - that captures patients´ preferences. The authors asked 20 experts to assess content validity and an additional 20 experts, patients and community members to examine face validity and guide revisions. Key revisions included shortening the length, clarifying constructs and providing details to explain the context and trade-offs necessary to balance the risks and benefits of cancer treatment. The content validity index for the final questionnaire was 1.0, indicating that all questions were relevant. Reviewers expressed that the questionnaire would serve an important purpose. Experts, patients and community members guided revisions of the questionnaire and documented its value.


Asunto(s)
Neoplasias/terapia , Prioridad del Paciente , Autoinforme , Humanos , Calidad de Vida , Reproducibilidad de los Resultados , Resultado del Tratamiento
11.
J Acquir Immune Defic Syndr ; 83(3): 251-259, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31913991

RESUMEN

BACKGROUND: Single summary scores, such as the Global Deficit Score, are often used to classify overall performance on neuropsychological batteries. The factor structure of test scores that underlie Global Deficit Score in studies of people living with HIV (PLWH) was assessed to determine whether individual test scores loaded onto a unitary factor to summarize performance. SETTING: Secondary data analysis on baseline data of PLWH from National NeuroAIDS Tissue Consortium and CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study. METHOD: Primary analyses included testing model structure and fit of neuropsychological test scores with confirmatory and exploratory factor analyses. Secondary analyses involved receiver operating characteristic curves, and associations with psychosocial and medical variables. RESULTS: Participants with confounds were excluded, leading to 798 (National NeuroAIDS Tissue Consortium) and 1222 (CHARTER) cases. When confirmatory factor analysis models were structured to be consistent with theoretically-based cognitive domains, models did not fit adequately. Per exploratory factor analyses, tests assessing speeded information processing, working memory, and executive functions loaded onto a single factor and explained the most variance in both cohorts. This factor tended to be associated with age, estimated premorbid ability, and aspects of substance use history. Its relation to age, in context of demographically corrected neuropsychological scores, suggested accelerated aging. CONCLUSION: Results indicate that individual neuropsychological tests did not load exactly onto expected domains, suggesting another framework for future analyses of cognitive domains. The possibility of a new index, and its use to assess cognitive impairment in PLWH, is suggested for further diagnostic and prognostic purposes.


Asunto(s)
Disfunción Cognitiva/complicaciones , Infecciones por VIH/complicaciones , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas
12.
Ann Surg ; 271(2): 296-302, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30188400

RESUMEN

OBJECTIVE: Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. BACKGROUND: Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). METHODS: The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. RESULTS: Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. CONCLUSIONS: Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.


Asunto(s)
Investigación Biomédica/economía , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Apoyo a la Investigación como Asunto , Adulto , Anciano , Femenino , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/cirugía , Humanos , Masculino , Persona de Mediana Edad , National Cancer Institute (U.S.) , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/cirugía , Programa de VERF , Análisis de Supervivencia , Estados Unidos , Neoplasias Pancreáticas
14.
Front Oncol ; 8: 157, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29868478

RESUMEN

Due to the ineffectiveness of chemoradiation and targeted therapy in esophageal anticancer care and the subsequent low survival rates, we constructed a high throughput method to discover and investigate new markers with prognostic, diagnostic, and therapeutic clinical utility. This was accomplished by developing a quick, inexpensive, and dependable platform to simultaneously quantify thousands of proteins which subsequently revealed novel markers involved in the pathogenesis of esophageal adenocarcinoma (EAC) via discovery mass spectrometry paired with conservative biostatistics. Our method uncovered a perfect storm of tumor suppressors being downregulated, proliferation markers ramped up, and chemoresistance markers overexpressed-many of which could serve as new therapy targets for EAC. The 12 markers discovered by this method are novel regarding their involvement in the pathogenesis of EAC. The molecular oncology arena now has a dozen new proteomic targets suitable for validation and elucidation of their clinical utility via gene knockdown in cellular and animal models. This new method can be replicated and applied to other cancers or disease states for research and development and discovery-based investigations. Our findings, which serve as a proof of concept, will hopefully motivate research groups to further expound on the molecular processes involved in the aggressiveness of EAC and other solid tumor diseases, ultimately leading to improved patient management strategies.

15.
Oncotarget ; 9(27): 19396-19405, 2018 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-29721211

RESUMEN

BACKGROUND: In contrast to other cancers, survival rates for pancreatic ductal adenocarcinoma (PDAC) patients have improved but minimally over the past thirty years. The aim of this study was to perform a meta-analysis of clinical trials published since 1986 to determine trends in median overall survival in primarily metastatic PDAC. MATERIALS AND METHODS: All Phase 2-4 clinical trials published during or after 1986 investigating first-line systemic chemotherapy in metastatic PDAC were included in the meta-analysis. Publications obtained through PubMed and www.ClinicalTrials.gov were cross-referenced to identify additional trials. Trials enrolling fewer than 50% of study participants with metastatic disease were excluded. RESULTS: Of 19,488 patients enrolled in 151 clinical trials, 84% had metastatic disease and 16% had locally advanced pancreatic cancer. In clinical trials published from 1986 to 2016, the weighted median overall survival (wMOS) increased by 3.0 months. The median wMOS was higher in combination therapy (7.31 months, IQR 5.4 to 8.5) compared to non-gemcitabine, single-agent therapy (4.76 months, IQR 3.5 to 6.0), gemcitabine monotherapy (6.48 months, IQR 5.9 to 7.2), and gemcitabine plus single-agent therapy (7.09 months, IQR 6.3 to 8.2). Of all regimens used in more than one study arm, FOLFIRINOX had the highest wMOS (10.9 months). CONCLUSIONS: Regardless of treatment regimen, survival rates in PDAC have minimally improved over time. Of drugs used in two or more study arms, only FOLFIRINOX has a wMOS greater than ten months. Emphasis should, therefore, be placed on identification of novel targets that promote early diagnosis and intervention. FUNDING: The authors on this manuscript are in parts, supported by grants from the National Institutes of Health (EDRN U01 CA200466, SPORE P50 CA127297, R01 CA183459, R21 AA026428 and R01 CA 195586).

16.
J Intensive Care Med ; 33(11): 635-644, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27913775

RESUMEN

BACKGROUND: The role of B-type natriuretic peptide (BNP) is less understood in the risk stratification of patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), especially in patients with normal left ventricular ejection fraction (LVEF). METHODS: This retrospective study from 2008 to 2012 evaluated all adult patients with AECOPD having BNP levels and available echocardiographic data demonstrating LVEF ≥40%. The patients were divided into groups 1, 2, and 3 with BNP ≤ 100, 101 to 500, and ≥501 pg/mL, respectively. A subgroup analysis was performed for patients without renal dysfunction. Outcomes included need for and duration of noninvasive ventilation (NIV) and mechanical ventilation (MV), NIV failure, reintubation at 48 hours, intensive care unit (ICU) and total length of stay (LOS), and in-hospital mortality. Two-tailed P < .05 was considered statistically significant. RESULTS: Of the total 1145 patients, 550 (48.0%) met our inclusion criteria (age 65.1 ± 12.2 years; 271 [49.3%] males). Groups 1, 2, and 3 had 214, 216, and 120 patients each, respectively, with higher comorbidities and worse biventricular function in higher categories. Higher BNP values were associated with higher MV use, NIV failure, MV duration, and ICU and total LOS. On multivariate analysis, BNP was an independent predictor of higher NIV and MV use, NIV failure, NIV and MV duration, and total LOS in groups 2 and 3 compared to group 1. B-type natriuretic peptide continued to demonstrate positive correlation with NIV and MV duration and ICU and total LOS independent of renal function in a subgroup analysis. CONCLUSION: Elevated admission BNP in patients with AECOPD and normal LVEF is associated with worse in-hospital outcomes and can be used to risk-stratify these patients.


Asunto(s)
Péptido Natriurético Encefálico/sangre , Evaluación del Resultado de la Atención al Paciente , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Función Ventricular Izquierda , Anciano , Biomarcadores/sangre , Cuidados Críticos , Progresión de la Enfermedad , Femenino , Mortalidad Hospitalaria , Humanos , Riñón/fisiopatología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Ventilación no Invasiva , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/terapia , Respiración Artificial , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Tiempo
17.
Am J Physiol Lung Cell Mol Physiol ; 314(3): L421-L431, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29097425

RESUMEN

Injurious dust exposures in the agricultural workplace involve the release of inflammatory mediators and activation of epidermal growth factor receptor (EGFR) in the respiratory epithelium. Amphiregulin (AREG), an EGFR ligand, mediates tissue repair and wound healing in the lung epithelium. Omega-3 fatty acids such as docosahexaenoic acid (DHA) are also known modulators of repair and resolution of inflammatory injury. This study investigated how AREG, DHA, and EGFR modulate lung repair processes following dust-induced injury. Primary human bronchial epithelial (BEC) and BEAS-2B cells were treated with an aqueous extract of swine confinement facility dust (DE) in the presence of DHA and AREG or EGFR inhibitors. Mice were exposed to DE intranasally with or without EGFR inhibition and DHA. Using a decellularized lung scaffolding tissue repair model, BEC recolonization of human lung scaffolds was analyzed in the context of DE, DHA, and AREG treatments. Through these investigations, we identified an important role for AREG in mediating BEC repair processes. DE-induced AREG release from BEC, and DHA treatment following DE exposure, enhanced this release. Both DHA and AREG also enhanced BEC repair capacities and rescued DE-induced recellularization deficits. In vivo, DHA treatment enhanced AREG production following DE exposure, whereas EGFR inhibitor-treated mice exhibited reduced AREG in their lung homogenates. These data indicate a role for AREG in the process of tissue repair after inflammatory lung injury caused by environmental dust exposure and implicate a role for DHA in regulating AREG-mediated repair signaling in BEC.


Asunto(s)
Anfirregulina/metabolismo , Bronquios/citología , Ácidos Docosahexaenoicos/farmacología , Polvo/análisis , Exposición a Riesgos Ambientales/efectos adversos , Células Epiteliales/citología , Lesión Pulmonar/prevención & control , Animales , Bronquios/efectos de los fármacos , Bronquios/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Receptores ErbB/metabolismo , Humanos , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Porcinos
18.
J Palliat Med ; 21(4): 452-462, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29173030

RESUMEN

BACKGROUND: Little is known about the composition, availability, integration, communication, perceived barriers, and work load of pediatric palliative care (PPC) providers serving children and adolescents with cancer. OBJECTIVE: To summarize the structure and services of programs to better understand successes and gaps in implementing palliative care as a standard of care. METHODS: Cross-sectional online survey about the palliative care domains determined by the Psychosocial Care of Children with Cancer and Their Families Workgroup. SUBJECTS: A total of 142 surveys were completed with representation from 18 countries and 39 states. RESULTS: Three-fourths of sites reported having a PPC program available for the pediatric cancer population at their center. Over one-fourth (28%) have been in existence less than five years. Fewer than half of sites (44%) offered 24/7 access to palliative care consultations. Neither hospital-based nor local community hospice services were available for pediatric patients at 24% of responding sites. A specific inpatient PPC unit was available at 8% of sites. Criteria for automatic palliative referrals ("trigger" diagnoses) were reported by 44% respondents. The presence of such "triggers" increased the likelihood of palliative principle introduction 3.41 times (p < 0.003). Six percent of respondents perceived pediatric oncology patients and their families "always" were introduced to palliative care concepts and 17% reported children and families "always" received communication about palliative principles. The most prevalent barriers to palliative care were at the provider level. DISCUSSION: Children and adolescents with cancer do not yet receive concurrent palliative care as a universal standard.


Asunto(s)
Neoplasias/terapia , Cuidados Paliativos/organización & administración , Grupo de Atención al Paciente/organización & administración , Pediatría/organización & administración , Estudios Transversales , Humanos , Encuestas y Cuestionarios
19.
Stem Cells ; 35(11): 2239-2252, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28792678

RESUMEN

Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma. Stem Cells 2017;35:2239-2252.


Asunto(s)
Glaucoma/genética , Proteínas de Homeodominio/genética , Células Madre Pluripotentes Inducidas/metabolismo , Células Ganglionares de la Retina/metabolismo , Transactivadores/genética , Alelos , Diferenciación Celular , Femenino , Expresión Génica , Glaucoma/fisiopatología , Humanos , Masculino , Células Ganglionares de la Retina/patología
20.
J Dent Educ ; 80(3): 275-80, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26933102

RESUMEN

The primary aim of this study was to determine the characteristics that current chairpersons in restorative dentistry, general dentistry, prosthodontics, and operative dentistry departments in U.S. dental schools feel are most relevant in contributing to their success. The secondary aim was to determine these individuals' rankings of the importance of a listed set of characteristics for them to be successful in their position. All 82 current chairs of the specified departments were invited to respond to an electronic survey. The survey first asked respondents to list the five most essential characteristics to serve as chair of a department and to rank those characteristics based on importance. Participants were next given a list of ten characteristics in the categories of management and leadership and, without being aware of the category of each individual item, asked to rank them in terms of importance for their success. A total of 39 chairpersons completed the survey (47.6% response rate; 83.3% male and 16.2% female). In section one, the respondents reported that leadership, vision, work ethic, integrity, communication, and organization were the most essential characteristics for their success. In section two, the respondents ranked the leadership characteristics as statistically more important than the management characteristics (p<0.0001) for being successful in their positions.


Asunto(s)
Personal Administrativo , Operatoria Dental/organización & administración , Liderazgo , Facultades de Odontología/organización & administración , Adulto , Anciano , Actitud del Personal de Salud , Carácter , Comunicación , Operatoria Dental/educación , Femenino , Odontología General/educación , Odontología General/organización & administración , Humanos , Relaciones Interprofesionales , Masculino , Persona de Mediana Edad , Cultura Organizacional , Objetivos Organizacionales , Prostodoncia/educación , Prostodoncia/organización & administración , Desarrollo de Personal , Estados Unidos
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