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1.
Adv Physiol Educ ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813606

RESUMO

With the rise of online instruction, a better understanding of the factors that contribute to belonging and motivation in these contexts is essential to creating optimal learning environments. Although group work is known to be beneficial to student success, few studies have investigated its role in the context of asynchronous online courses. The present study addresses this gap through a survey of 146 undergraduate students in an asynchronous online physiology lab over two semesters, one with required group work and one without group work. Students were surveyed to evaluate the influence of group work on their motivation and sense of belonging, as well as their perceptions of inclusive and exclusive features of the course. Students assigned to groups had a higher sense of belonging (P = 0.006) and beliefs about their competence (P = 0.002) and perceived lower effort and psychological costs associated with the course (P = 0.04 and 0.04 respectively) compared to students not assigned to groups. Students assigned to groups reported that peer interactions made them feel included in the course (70% of coded responses) while those not assigned to groups valued instructor interactions (51% of coded responses) as inclusive. Negative peer interactions were commonly reported as exclusive by students assigned to groups (28% of coded responses) while a lack of peer interactions (23% of coded responses) made students not assigned to groups feel excluded. These data indicate that assigning groups in asynchronous online courses is an effective way to increase student motivation and perceptions of belonging.

2.
J Sport Rehabil ; 31(1): 53-59, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560667

RESUMO

CONTEXT: Strength deficits and decreased scores on generic, dimension-specific, and region-specific health-related quality of life (HRQL) PRO measures are commonly documented among individuals with chronic ankle instability (CAI). However, it is unknown if there is a relationship between hip strength and self-reported patient-reported outcome (PRO) scores. OBJECTIVE: To compare isometric peak torque for hip-extension (H-EXT) and hip-abduction (H-ABD), as well as PRO scores between CAI, lateral ankle sprain copers (LAS copers), and uninjured controls (UC). The secondary purpose was to examine the relationship between isometric hip peak torque and PROs in participants with CAI. DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS: Sixty-three individuals, 45 women (23.02 [3.83] y, 165.91 [7.55] cm, 67.28 [11.95] kg) and 18 men (26.28 [5.43] y, 179.28 [9.01] cm, 83.87 [13.26] kg), grouped as uninjured control (n = 26), LAS coper (n = 15), or CAI (n = 22). MAIN OUTCOME MEASURES: The Foot and Ankle Ability Measure was used to assess region-specific HRQL. The Fear Avoidance Beliefs Questionnaire was used to assess injury-related fear. The Disablement in Physically Active was used to assess global HRQL. Isometric peak torque was measured with a handheld dynamometer for H-EXT and H-ABD. RESULTS: No group differences were observed for H-ABD (P = .34) or H-EXT (P = .35). The CAI group had significantly worse scores on all PROs compared with LAS coper (P < .001) and HC (P < .001). Moderate-weak correlations were found between H-ABD and Foot and Ankle Ability Measure-activities of daily living (P = .047; ρ = .392) and Foot and Ankle Ability Measure-Sport (P = .013; ρ = .482) and H- EXT and Fear Avoidance Beliefs Questionnaire-Work (P = .007; ρ = -.517). CONCLUSIONS: Individuals with CAI displayed lower HRQL based on worse scores on generic, dimension-specific, and region-specific PROs compared with LAS copers and uninjured controls. There were no significant between-group differences for H-EXT and H-ABD isometric peak torque production, but there was a moderate positive relationship between isometric H-ABD and self-reported ankle disability in individuals with CAI.


Assuntos
Tornozelo , Instabilidade Articular , Atividades Cotidianas , Articulação do Tornozelo , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida
3.
J Neurooncol ; 144(1): 179-191, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254264

RESUMO

INTRODUCTION: Brain tumor treatment and survival information is generally limited in large-scale cancer datasets. We provide a clinical investigation of current patterns of care and survival estimates for central nervous system (CNS) tumors treated in the United States. METHODS: We analyzed the National Cancer Database from 2004-2015 for all patients with diagnosis of primary CNS tumors. We describe patient demographics, treatment modality, and analyzed survival estimates. RESULTS: 512,168 patient tumor records were examined. The most common histology was meningioma (43.6%), followed by glioblastoma (22.0%), and nerve sheath tumors (10.6%). Patients had a median age of 60 years, with a female (57.9%), white (85.0%), and non-Hispanic (87.8%) predominance. Tumors were reported as World Health Organization (WHO) grade I for 55.9% of the patients, grade II for 5.9%, grade III for 4.4%, grade IV for 24.3%, and grade unknown or not applicable for 9.4%. Overall, 56% underwent surgical procedures, 30.4% received radiation, and 20.6% received chemotherapy. Radiation plus chemotherapy and surgery was the most common treatment modality in high-grade tumors (40.5% in WHO grade III and 49.3% in WHO grade IV), while surgery only or watchful waiting was preferred in low-grade tumors. Older age, male gender, non-Hispanic origin, higher number of comorbidities, and lower socioeconomic status were identified as risk factors for mortality. CONCLUSIONS: Our analysis provides long-term survival estimates and initial treatment decisions for patients with CNS tumors in hospitals throughout the United States. Age, comorbidities, gender, ethnicity, and socioeconomic characteristics were determinants of survival.


Assuntos
Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/classificação , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
4.
Am J Addict ; 24(6): 492-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26039514

RESUMO

Background and Objectives This study evaluated whether impulsivity (delay discounting and BIS-11-A) is associated with adolescent smoking status in a region with strong environmental risk factors for smoking. Methods Forty-two adolescent smokers and nonsmokers from rural Appalachia completed discounting and self-reported impulsivity assessments. Results The BIS-11-A, but not the measure of discounting, was associated with smoking status; however, neither assessment predicted smoking status once parent/best-friend smoking variables were statistically accounted for. Discussion and Conclusions In regions with strong environmental risk factors for smoking, delay discounting may play a more limited role in risk of initiation. Scientific Significance Helps to better define impulsivity as risk factors for smoking in relation to familial and broader cultural variables.


Assuntos
Comportamento do Adolescente/psicologia , Desvalorização pelo Atraso , Comportamento Impulsivo , População Rural/estatística & dados numéricos , Fumar/psicologia , Adolescente , Região dos Apalaches/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Risco , Autorrelato , Adulto Jovem
5.
Prev Med ; 58: 70-4, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24212061

RESUMO

OBJECTIVE: This report describes findings from a randomized controlled trial of an intervention to increase colorectal cancer (CRC) screening in primary care practices in Appalachian Kentucky. METHODS: Sixty-six primary care practices were randomized to early or delayed intervention groups. The intervention was provided at practices using academic detailing, a method of education where providers receive information on a specific topic through personal contact. Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention. RESULTS: A total of 3844 medical records were reviewed at baseline and 3751 at the six-month follow-up. At baselines, colonoscopy was recommended more frequently (43.4%) than any other screening modality, followed by fecal occult blood testing (18.0%), flexible sigmoidoscopy (0.4%), and double-contrast barium enema (0.3%). Rates of documented screening results were higher for all practices at the six-month follow-up for colonoscopy (31.8% vs 29.6%) and fecal occult blood testing (12.2% vs 11.2%). For early intervention practices that recommended screening, colonoscopy rates increased by 15.7% at six months compared to an increase of 2.4% in the delayed intervention practices (p=.01). CONCLUSIONS: Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/normas , Médicos de Atenção Primária/normas , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Região dos Apalaches , Colonoscopia , Estudos Transversais , Aconselhamento Diretivo/normas , Aconselhamento Diretivo/estatística & dados numéricos , Detecção Precoce de Câncer/normas , Feminino , Seguimentos , Humanos , Kentucky , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Sigmoidoscopia , Adulto Jovem
6.
World Neurosurg ; 182: e400-e404, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38030073

RESUMO

OBJECTIVE: To evaluate the relationships between Doximity rankings (Doximity, Inc.) of residency programs and 2 new ranking systems based on publication rates and academic pursuits. METHODS: We collected data on 550 neurosurgery graduates over 3 years. We analyzed the median number of published manuscripts per resident and the percentage of residents pursuing academic careers and compared them across the Doximity Research Productivity and Reputation Rankings. We used logistic regression to evaluate the relationships among the rankings, publication rates, and academic pursuits. RESULTS: Neurosurgery residents published a median of 10 manuscripts per person (IQR: 6-17), and 50% (IQR: 33%-67%) of residents in a given program pursued an academic career. The distributions of the median number of published manuscripts across the Doximity Research Productivity Ranking and the Doximity Reputation Ranking tiers differed significantly (all P < 0.001). Similarly, the distribution of the percentage of residents pursuing an academic career across both published Doximity ranking systems' tiers differed significantly (all P = 0.02). Moreover, we found moderate agreement between the 2 Doximity rankings, fair agreement between the publication and the other 3 rankings, and slight agreement between the academic pursuit and the Doximity rankings. CONCLUSIONS: We introduced 2 new methods to rank residency programs based on the number of graduates pursuing an academic position and the median number of published manuscripts per resident. By taking a comprehensive approach, neurosurgery applicants can ensure that they select a residency program that meets their needs and offers them the best opportunity for success.


Assuntos
Internato e Residência , Neurocirurgia , Humanos , Neurocirurgia/educação , Reprodutibilidade dos Testes , Eficiência
7.
JPEN J Parenter Enteral Nutr ; 47(7): 888-895, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37345259

RESUMO

BACKGROUND: Patients who are critically ill may receive suboptimal nutrition that leads to weight loss and increased risk of functional deficits. METHODS: Our overarching hypothesis is that nutrition in the intensive care unit (ICU) and the early recovery phase associates with functional outcomes at short-term follow-up. We enrolled adult patients who attended the University of Kentucky ICU recovery clinic (ICU-RC) from November 2021 to June 2022. Patients participated in muscle and functional assessments. Nutrition intake and status during the ICU stay were analyzed. The Subjective Global Assessment and a nutrition questionnaire were used to identify changes in intake, ongoing gastrointestinal symptoms, and patient's access to food at the ICU-RC appointment. RESULTS: Forty-one patients enrolled with a median hospital length of stay (LOS) of 23 days. Patients with 0 days of nil per os (NPO) status throughout hospitalization had a shorter LOS (P = 0.05), were able to complete the five times sit-to-stand test (P = 0.02), and were less likely to experience ICU-acquired weakness (P = 0.04) at short-term follow-up compared with patients with ≥1 day of NPO status. Twenty (48%) patients reported changes in nutrition intake in early recovery compared with before hospitalization. Eight (20%) patients reported symptoms leading to decreased intake and four (10%) reported access to food as a barrier to intake. CONCLUSION: Barriers to nutrition exist during critical illness and persist after discharge, with almost half of patients reporting a change in intake. Inpatient nutrition intake is associated with functional outcomes and warrants further exploration.


Assuntos
Estado Terminal , Estado Nutricional , Adulto , Humanos , Estudos Prospectivos , Unidades de Terapia Intensiva , Tempo de Internação , Sobreviventes
8.
Microbiol Spectr ; 10(5): e0269322, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36094219

RESUMO

The rise in infections caused by antibiotic-resistant bacteria is outpacing the development of new antibiotics. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are a group of clinically important bacteria that have developed resistance to multiple antibiotics and are commonly referred to as multidrug resistant (MDR). The medical and research communities have recognized that, without new antimicrobials, infections by MDR bacteria will soon become a leading cause of morbidity and death. Therefore, there is an ever-growing need to expedite the development of novel antimicrobials to combat these infections. Toward this end, we set out to refine an existing mouse model of pulmonary Pseudomonas aeruginosa infection to generate a robust preclinical tool that can be used to rapidly and accurately predict novel antimicrobial efficacy. This refinement was achieved by characterizing the virulence of a panel of genetically diverse MDR P. aeruginosa strains in this model, by both 50% lethal dose (LD50) analysis and natural history studies. Further, we defined two antibiotic regimens (aztreonam and amikacin) that can be used as comparators during the future evaluation of novel antimicrobials, and we confirmed that the model can effectively differentiate between successful and unsuccessful treatments, as predicted by in vitro inhibitory data. This validated model represents an important tool in our arsenal to develop new therapies to combat MDR P. aeruginosa strains, with the ability to provide rapid preclinical evaluation of novel antimicrobials and support data from clinical studies during the investigational drug development process. IMPORTANCE The prevalence of antibiotic resistance among bacterial pathogens is a growing problem that necessitates the development of new antibiotics. Preclinical animal models are important tools to facilitate and speed the development of novel antimicrobials. Successful outcomes in animal models not only justify progression of new drugs into human clinical trials but also can support FDA decisions if clinical trial sizes are small due to a small population of infections with specific drug-resistant strains. However, in both cases the preclinical animal model needs to be well characterized and provide robust and reproducible data. Toward this goal, we have refined an existing mouse model to better predict the efficacy of novel antibiotics. This improved model provides an important tool to better predict the clinical success of new antibiotics.


Assuntos
Amicacina , Pseudomonas aeruginosa , Camundongos , Humanos , Animais , Amicacina/farmacologia , Aztreonam/farmacologia , Testes de Sensibilidade Microbiana , Drogas em Investigação/farmacologia , Farmacorresistência Bacteriana Múltipla , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias
9.
Transl Res ; 231: 13-23, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33460824

RESUMO

Oligodendrocyte progenitor cells (OPCs) in the infant brain give rise to mature oligodendrocytes that myelinate CNS axons. OPCs are particularly vulnerable to oxidative stress that occurs in many forms of brain injury. One common cause of infant brain injury is neonatal intraventricular hemorrhage (IVH), which releases blood into the CSF and brain parenchyma of preterm infants. Although blood contains the powerful oxidant hemoglobin, the direct effects of hemoglobin on OPCs have not been studied. We utilized a cell culture system to test if hemoglobin induced free radical production and mitochondrial dysfunction in OPCs. We also tested if phenelzine (PLZ), an FDA-approved antioxidant drug, could protect OPCs from hemoglobin-induced oxidative stress. OPCs were isolated from Sprague Dawley rat pups and exposed to hemoglobin with and without PLZ. Outcomes assessed included intracellular reactive oxygen species levels using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent dye, oxygen consumption using the XFe96 Seahorse assay, and proliferation measured by BrdU incorporation assay. Hemoglobin induced oxidative stress and impaired mitochondrial function in OPCs. PLZ treatment reduced hemoglobin-induced oxidative stress and improved OPC mitochondrial bioenergetics. The effects of hemoglobin and PLZ on OPC proliferation were not statistically significant, but showed trends towards hemoglobin reducing OPC proliferation and PLZ increasing OPC proliferation (P=0.06 for both effects). Collectively, our results indicate that hemoglobin induces mitochondrial dysfunction in OPCs and that antioxidant therapy reduces these effects. Therefore, antioxidant therapy may hold promise for white matter diseases in which hemoglobin plays a role, such as neonatal IVH.


Assuntos
Hemoglobinas/farmacologia , Mitocôndrias/efeitos dos fármacos , Oligodendroglia/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , L-Lactato Desidrogenase , Mitocôndrias/metabolismo , Consumo de Oxigênio , Fenelzina/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Células-Tronco
10.
Exp Neurol ; 337: 113597, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33422552

RESUMO

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue sparing, reduced ROS-associated 3-nitrotyrosine (3-NT) accumulation, and improved anatomical and functional recovery in 14-MO SCI-mice. By directly comparing the effects of DNP between ages we demonstrate that mitochondrial contributions to neurodegeneration diverge with age after SCI. Collectively, our data indicate an essential role of mitochondria in age-associated neurodegeneration.


Assuntos
Envelhecimento , Mitocôndrias/metabolismo , Traumatismos da Medula Espinal/patologia , 2,4-Dinitrofenol/farmacologia , Animais , Sobrevivência Celular , Progressão da Doença , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Neurônios/patologia , Estresse Oxidativo , Consumo de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/complicações , Tirosina/análogos & derivados , Tirosina/metabolismo , Desacopladores/farmacologia
11.
Cancer Epidemiol ; 60: 16-22, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30878798

RESUMO

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States. METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma. RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in community facilities, had higher Charlson-Deyo score, and a lower rate of private insurance. Watchful waiting was the most common treatment modality (46.7%), followed by surgery only (40%). Grade II and III patients were more likely to receive therapy. Watchful waiting increased from 35.2% in 2004 to 51.4% in 2014. Younger age, male gender, private insurance, and treatment in academic facilities were determinants for receipt of surgery and/or radiation. Median survival was 12.6 years, higher in histologically confirmed cases (13.1 years). Older patients, Blacks, males, those that received radiation plus surgery, and were treated in community facilities had an increased risk of mortality. CONCLUSIONS: Over half of patients were diagnosed by imaging, suggesting a higher role of clinical determinants over histological confirmation in treatment decisions. Watchful waiting as initial management is increasing. Our survival analysis favored histological confirmation. Patients receiving radiation and surgery had an increased risk of mortality.


Assuntos
Bases de Dados Factuais , Neoplasias Meníngeas/terapia , Meningioma/terapia , Conduta Expectante , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Meningioma/mortalidade , Meningioma/patologia , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores Socioeconômicos , Taxa de Sobrevida , Estados Unidos , Adulto Jovem
12.
Addict Behav ; 90: 334-340, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30508743

RESUMO

BACKGROUND: Behavioral measures of impulsive behavior include the dimensions of behavioral disinhibition, decision-making, and lapses of attention. These behaviors are associated with a range of risky activities during adolescence, including cigarette smoking; however, few studies have evaluated their associations with tobacco treatment outcomes. The current study examined the relationship between impulsive behavior and contingency management treatment outcomes for adolescent smokers. METHODS: Data from two contingency management smoking cessation trials were combined (N = 189 adolescents). Participants provided breath carbon monoxide (CO) samples with incentives delivered contingent (i.e., active treatment [AT] condition) or non-contingent (i.e., control treatment [CT] condition) on CO level. Dimensions of impulsive behavior were assessed pre- and post-treatment using the Go/Stop Task, a measure of delay discounting, a continuous performance task, while self-reported impulsivity was assessed with the Barratt Impulsiveness Scale-Adolescent. Relationships between impulsive behavior and treatment outcomes (efficacy and adherence) were assessed using linear mixed effects models. RESULTS: Participants in the AT condition had significantly lower program CO levels at each treatment phase. Delay discounting in the AT condition predicted CO levels, with those discounting the most lowering their breath CO levels the least. Delay discounting also predicted program adherence across both conditions. CONCLUSIONS: Delay discounting may be the most relevant dimension of impulsive behavior to predict outcomes for adolescent smokers completing CM programs, both in terms of successful reductions in smoking and program adherence. Suggestions are made to reduce the effects of delay discounting for adolescent smokers using this treatment approach.


Assuntos
Comportamento do Adolescente/psicologia , Terapia Comportamental/métodos , Comportamento Impulsivo , Fumantes/psicologia , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Adolescente , Desvalorização pelo Atraso , Feminino , Humanos , Masculino , Fumar/psicologia , Resultado do Tratamento
13.
PLoS One ; 14(2): e0212340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30811496

RESUMO

Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies.


Assuntos
Água Potável/análise , Cabelo/química , Neoplasias Pulmonares/epidemiologia , Unhas/química , Oligoelementos/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Região dos Apalaches/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Kentucky/epidemiologia , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
PLoS One ; 13(9): e0203639, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30235224

RESUMO

BACKGROUND: Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States. METHODS: We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma. RESULTS: We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most common primary site location was the cerebrum (79.9%). Overall, 72.2% received surgery, 36.0% radiation, and 27.3% chemotherapy. Treatment combinations included surgery only (41.5%), chemotherapy + surgery (6.6%), chemotherapy only (3.1%), radiation + chemotherapy + surgery (10.7%), radiation + surgery (11.5%), radiation only (6.1%), and radiotherapy + chemotherapy (6.7%). Radiation was more common in treatment of elderly patients, 1p/19q co-deletion (37.3% versus 24.3%, p<0.01), and tumors with midline location. Median survival was 11 years with younger age, 1p/19q co-deletion, and cerebrum location offered survival advantage. CONCLUSIONS: Tumor location, 1p/19q co-deletion, and age were the main determinants of treatment received and survival, likely reflecting tumor biology differences. Any form of treatment was preferred over watchful waiting in the majority of the patients (86.1% versus 8.1%). Survival of low-grade gliomas is higher than previously reported in the majority of clinical trials and population-based analyses. Our analysis provides a real world estimation of treatment decisions, use of molecular data, and outcomes.


Assuntos
Glioma/tratamento farmacológico , Glioma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 19/genética , Feminino , Glioma/metabolismo , Glioma/radioterapia , Humanos , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Med Oncol ; 35(10): 136, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30155806

RESUMO

There are limited treatment modalities after high-grade gliomas recurrence. MGMT depletion modulated by dose-dense temozolomide (ddTMZ) remains a debated therapy for initial TMZ responders. Patients were selected retrospectively from our practice with diagnosis of high-grade gliomas (WHO grade III or IV), and were followed since the start of ddTMZ until death or change of therapy. Twenty-one patients were reviewed, with a median age of 47 (25-61) years and a median of 5.8 (1.5-38.8) cycles of ddTMZ. The majority were males (71.4%). Sixty-six percent received 21 on/28 off ddTMZ schedule, 28.6% daily, and 1 patient received a 7 days on/7 days off schedule. IDH mutation status was available for 18 (85.7%) patients, with 7 (33.3%) IDH mutant and 11 (52.5%) IDH wild type. MGMT methylation was assessed in 6 (28.6%) of the patients, being MGMT methylated in 3 (14.3%) patients, and non-methylated in 3 (14.3%) patients. The majority of patients (57.1%) were receiving ddTMZ in addition to other forms of therapy, including either bevacizumab (38.1%) or tumor-treating fields (TTFields) (19.1%). Overall ddTMZ was well tolerated, with few adverse events reported. The estimated median overall survival after ddTMZ start was 11 months. Median progression-free survival (PFS) was 6 months. Outcomes did not vary between patients receiving ddTMZ alone or those using TTFields or bevacizumab as concomitant therapy, but there was a trend to longer survival with the use of concomitant TTFields. Our results demonstrate benefit of ddTMZ after previous treatment with standard TMZ dosing with no apparent increase in treatment-related toxicities. In summary, ddTMZ should be considered in TMZ responsive patients and warrants further investigation.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Temozolomida/administração & dosagem , Adulto , Neoplasias Encefálicas/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Glioma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Gradação de Tumores/tendências , Recidiva Local de Neoplasia/diagnóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências
16.
Clin Cancer Res ; 23(24): 7550-7557, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28974547

RESUMO

Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan-Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage.Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08-1.72, P = 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84-1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190.Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors. Clin Cancer Res; 23(24); 7550-7. ©2017 AACR.


Assuntos
Predisposição Genética para Doença , Diester Fosfórico Hidrolases/genética , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores Tumorais/genética , Reparo do DNA/genética , Feminino , Genótipo , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida , Resultado do Tratamento
17.
Exp Clin Psychopharmacol ; 23(6): 486-93, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26280592

RESUMO

Cigarette smoking among adolescents remains a significant public health concern. This problem is compounded in regions such as rural Appalachia where rates of smoking are consistently higher than national averages and access to treatments is limited. The current research evaluated a home-based contingency management program completed over the Internet with adolescent smokers recruited from rural Appalachia. Participants (N = 62) submitted 3 video recordings per day showing their breath carbon monoxide (CO) levels using a handheld CO monitor. Participants were assigned to either an active treatment condition (AT; n = 31) in which reductions in breath CO were reinforced or a control treatment condition (CT; n = 31) in which providing timely video recordings were reinforced with no requirement to reduce breath CO. Results revealed that participants in the AT condition reduced their breath CO levels significantly more so during treatment than participants in the CT condition. Within-group comparisons revealed that participants in both conditions significantly reduced their breath CO, self-reported smoking, and nicotine dependence ratings during treatment. However, only participants in the AT condition significantly reduced urinary cotinine levels during treatment, and only participants in this condition maintained all reductions until 6-week post treatment. Participants in the CT condition only maintained self-reported smoking reductions until posttreatment assessments. These results support the feasibility and initial efficacy of this incentive-based approach to smoking cessation with adolescent smokers living in rural locations.


Assuntos
Terapia Comportamental/métodos , Reforço Psicológico , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Tabagismo/terapia , Adolescente , Região dos Apalaches , Testes Respiratórios , Monóxido de Carbono/análise , Estudos de Viabilidade , Feminino , Humanos , Internet , Masculino , Motivação , Saúde da População Rural , População Rural , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Tabagismo/psicologia
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