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1.
Gerontology ; 69(8): 1002-1013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36966524

RESUMO

INTRODUCTION: Identifying responsive outcome measures for assessing functional change related to cognition, communication, and quality of life for individuals with neurodegenerative disease is important for intervention design and clinical care. Goal Attainment Scaling (GAS) has been used as an outcome measure to formally develop and systematically measure incremental progress toward functional, patient-centered goals in clinical settings. Evidence suggests that GAS is reliable and feasible for use in older adult populations and in adult populations with cognitive impairment, but no review has assessed the suitability of GAS in older adults with neurodegenerative disease experiencing dementia or cognitive impairment, based on responsiveness. This study conducted a systematic review to evaluate the suitability of GAS as an outcome measure for older adult populations with neurodegenerative disease experiencing dementia or cognitive impairment, based on responsiveness. METHODS: The review was registered with PROSPERO and performed by searching ten electronic scientific databases (PubMed, Medline OVID, CINAHL, Cochrane, Embase, Web of Science, PsycINFO, Scopus, OTSeeker, REHABDATA) and four registries (Clinicaltrials.gov, Grey Literature Report, Mednar, OpenGrey). A summary measure of responsiveness (post-intervention minus pre-intervention mean GAS T-score) was compared across eligible studies using a random-effects meta-analysis. Risk of bias in included studies was assessed using the NIH Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. RESULTS: 882 eligible articles were identified and screened by two independent reviewers. Ten studies met inclusion criteria for the final analysis. Of the ten included reports, 3 focus on all-cause dementia, 3 on multiple sclerosis, 1 on Parkinson's disease, 1 on mild cognitive impairment, 1 on Alzheimer's disease, and 1 on primary progressive aphasia. Responsiveness analyses showed pre- and post-intervention GAS goals were significantly different from zero (Z = 7.48, p < 0.001), with post-intervention GAS scores being higher than pre-intervention GAS scores. Three included studies showed a high risk of bias, 3 showed a moderate risk of bias, and 4 showed a low risk of bias. Overall risk of bias of included studies was rated as moderate. CONCLUSION: GAS showed an improvement in goal attainment across different dementia patient populations and intervention types. The overall moderate risk of bias suggests that while bias is present across included studies (e.g., small sample size, unblinded assessors), the observed effect likely represents the true effect. This suggests that GAS is responsive to functional change and may be suitable for use in older adult populations with neurodegenerative disease experiencing dementia or cognitive impairment.


Assuntos
Disfunção Cognitiva , Demência , Doenças Neurodegenerativas , Humanos , Idoso , Demência/terapia , Qualidade de Vida , Objetivos , Disfunção Cognitiva/terapia
2.
Pediatr Blood Cancer ; 69(6): e29613, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35322524

RESUMO

OBJECTIVE: To compare outcomes of obese and nonobese pediatric patients with acute promyelocytic leukemia (APL) from the Cancer and Leukemia Group B trial (CALGB) 9710 and the Children's Oncology Group trial AAML0631. METHODS: Data including demographics, adverse events, overall and event-free survival (EFS) were analyzed. RESULTS: The prevalence of obesity was 34% on C9710 and 35% on AAML0631. There was significantly lower overall and EFS in the obese population on multivariable analysis on AAML0631 but not on CALGB 9710. Eleven patients died during therapy or in follow-up. CONCLUSION: The prevalence of obesity is higher in pediatric patients with APL compared to the general population. The decreased EFS and OS in obese patients on AAML0631 suggest that the presence of obesity can influence outcomes using the most current treatment. These findings support the need for further research on the potential role of obesity in pediatric APL leukemogenesis.


Assuntos
Leucemia Promielocítica Aguda , Obesidade Infantil , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Intervalo Livre de Doença , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Prevalência , Prognóstico , Resultado do Tratamento
3.
Cancer ; 125(20): 3615-3622, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31355924

RESUMO

BACKGROUND: Significant disparities exist in colorectal cancer (CRC) screening rates among those of low socioeconomic status, with fewer years of education, lacking health insurance, or living in rural areas. METHODS: A randomized controlled trial was conducted to compare the effectiveness of 2 follow-up approaches to a health literacy intervention to improve CRC screening: automated telephone call or personal call. Patients aged 50 to 75 years residing in 4 rural community clinics in Louisiana were given a structured interview that assessed demographic, health literacy and CRC screening barriers, knowledge, and attitudes. All were given health literacy-informed CRC education, a patient-friendly CRC screening pamphlet, simplified fecal immunochemical test (FIT) instructions, and a FIT kit, and a "teach-back" method was used to confirm understanding. Patients were randomized to 1 of 2 telephone follow-up arms. If they did not mail their FIT kit within 4 weeks, they received a reminder call and were called again at 8 weeks if the test still was not received. RESULTS: A total of 620 patients were enrolled. Approximately 55% were female, 66% were African American, and 40% had limited literacy. The overall FIT completion rate was 68%: 69.2% in the automated telephone call arm and 67% in the personal call arm. Greater than one-half of the patients (range, 58%-60%) returned the FIT kit without receiving a telephone call. There was no difference noted with regard to the effectiveness of the follow-up calls; each increased the return rate by 9%. CONCLUSIONS: Providing FIT kits and literacy-appropriate education at regularly scheduled clinic visits with a follow-up telephone call when needed was found to increase CRC screening among low-income, rural patients. The lower cost automated call was just as effective as the personal call.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Programas de Rastreamento/métodos , População Rural/estatística & dados numéricos , Idoso , Instituições de Assistência Ambulatorial , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Fezes/química , Feminino , Seguimentos , Educação em Saúde/estatística & dados numéricos , Letramento em Saúde , Humanos , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Telefone
4.
Oncologist ; 24(8): 1039-e642, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31138725

RESUMO

LESSONS LEARNED: Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three-drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting.The DOF regimen represents an alternative to the FLOT (5-FU 2,600 mg/m2 as 24-hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting. BACKGROUND: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum-taxane-fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5-FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. METHODS: Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5-FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR). RESULTS: Forty-four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty-three patients (76.7%) received at least seven cycles (7-34). Grade 3-4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months. CONCLUSION: DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Fluoruracila/administração & dosagem , Oxaliplatina/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Intervalo Livre de Doença , Docetaxel/efeitos adversos , Esquema de Medicação , Junção Esofagogástrica/patologia , Estudos de Viabilidade , Feminino , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Síndromes Neurotóxicas/epidemiologia , Síndromes Neurotóxicas/etiologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Oxaliplatina/efeitos adversos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo
5.
Breast Cancer Res Treat ; 176(1): 95-100, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977026

RESUMO

PURPOSE: Determining the need for adjuvant chemotherapy in estrogen receptor (ER)+ disease can be influenced by pathological characteristics and gene expression assays [i.e., Oncotype Dx recurrence scores (RSs)]. The primary objective of this study is to investigate the relationship between the RSs and pathological markers in younger (< 50) versus older (≥ 50) women with early-stage node-negative ER+ breast cancer. METHODS: This was a single academic-center retrospective cohort study. Subjects who underwent Oncotype gene expression testing were retrospectively and sequentially identified. 436 Subjects were identified of which 344 were eligible for analysis (133 younger subjects < 50 years of age, and 211 older subjects ≥ 50 years). Pathological data assessed included the progesterone receptor (PR), histological grade (grade), Ki-67, and P53. A multivariable regression analysis was performed using age, PR, and grade as predictor variables for RS. Adjusted R2 was determined. To investigate the primary objective, subjects were stratified based on age, PR, and grade status in that sequence. Within each tumor subtype as determined by PR and grade statuses, the RSs in the younger versus older age group were compared using Student's t-test and the differences in the 95% confidence interval limits in RS means calculated. Age influence on adjuvant chemotherapy recommendation was also assessed by stratifying subjects based on age (< 50 vs. ≥ 50) and then by RS risk group (≤ 10, 11-25, ≥ 26). Subsequently, the proportions of younger versus older subjects within identical RS risk groups who were explicitly advised by their oncologist to proceed with chemotherapy as documented in their electronic health records were compared using χ2 test. RESULTS: Based on the multivariable regression analysis, the adjusted R2 was 0.229232 and RS was found to be independent of age (p = 0.7169). Between younger and older subjects with tumors with similar PR and grade pathological features, the differences in the RS were insignificant (p > 0.05). Chemotherapy was recommended in younger versus older women, in 0% when the RS was ≤ 10, 39% and 40% when the RS was 11-25 (p = 0.82), and 100% and 98% when the RS was ≥ 26 (p = 0.51), respectively. CONCLUSIONS: The relationship between pathological features and RS is consistent irrespective of age; therefore, models predicting RS may be applicable irrespective of age.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Expressão Gênica , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Adulto , Fatores Etários , Idoso , Algoritmos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Gerenciamento Clínico , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
6.
Echocardiography ; 36(11): 2033-2040, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31705570

RESUMO

BACKGROUND: Patients with acute myeloid leukemia (AML) are surviving longer. There are no data on changes in myocardial mechanics from standard of care low-dose anthracycline-based induction chemotherapy in older patients with AML. The aim of this study was to demonstrate the potential utility of strain imaging in detecting early changes in left ventricular function in this patient population after induction chemotherapy. METHODS: Thirty two patients enrolled in the ECOG-ACRIN E2906 study (cytarabine and daunorubicin vs clofarabine [Genzyme/Sanofi]) from 2011 to 2014 were evaluated retrospectively. Two-dimensional transthoracic echocardiography (TTE) imaging with Doppler and two-dimensional speckle-tracking echocardiography (2DSTE) using EchoInsight software (Epsilon imaging) were performed before and after induction chemotherapy. RESULTS: Eighteen patients received cytarabine and daunorubicin (7 + 3) and 14 received clofarabine. The clofarabine group was older than the 7 + 3 cohort (67.8 ± 4.0 vs 63.7 ± 3.8, P = .007). There were no other significant differences in cardiac risk factors between groups. The 7 + 3 group had a decrease in average peak systolic global longitudinal (-19.1 ± 2.8 to -17.2 ± 3.0, P = .01) and circumferential strain (-29.4 ± 6.3 to -23.9 ± 4.3, P = .011). These changes were not demonstrated in the clofarabine group and were not associated with a decline in left ventricular ejection fraction (LVEF). CONCLUSIONS: In older AML patients, standard cytarabine and daunorubicin chemotherapy causes early changes in global longitudinal and circumferential strain not seen with clofarabine therapy. These findings demonstrate subclinical left ventricular dysfunction after exposure to low cumulative doses of anthracycline-based induction chemotherapy and may help us better identify those patients at risk for adverse long-term cardiovascular outcomes.


Assuntos
Clofarabina/efeitos adversos , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Ecocardiografia/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Cardiotoxicidade , Clofarabina/uso terapêutico , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
7.
Alzheimers Dement ; 15(4): 543-552, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30765195

RESUMO

INTRODUCTION: Primary progressive aphasia (PPA) displays variable progression trajectories that require further elucidation. METHODS: Longitudinal quantitation of atrophy and language over 12 months was completed for PPA patients with and without positive amyloid PET (PPAAß+ and PPAAß-), an imaging biomarker of underlying Alzheimer's disease. RESULTS: Over 12 months, both PPA groups showed significantly greater cortical atrophy rates in the left versus right hemisphere, with a more widespread pattern in PPAAß+. The PPAAß+ group also showed greater decline in performance on most language tasks. There was no obligatory relationship between the logopenic PPA variant and amyloid status. Effect sizes from quantitative MRI data were more robust than neuropsychological metrics. DISCUSSION: Preferential language network neurodegeneration is present in PPA irrespective of amyloid status. Clinical and anatomical progression appears to differ for PPA due to Alzheimer's disease versus non-Alzheimer's disease neuropathology, a distinction that may help to inform prognosis and the design of intervention trials.


Assuntos
Doença de Alzheimer/patologia , Afasia Primária Progressiva , Atrofia/patologia , Encéfalo/patologia , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/genética , Afasia Primária Progressiva/diagnóstico por imagem , Afasia Primária Progressiva/patologia , Biomarcadores , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
8.
Breast Cancer Res Treat ; 171(2): 371-381, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29850984

RESUMO

PURPOSE: Activation of the phosphoinositide 3-kinase (PI3K) pathway is an important resistance mechanism to anti-HER2 therapies. This study aimed to assess the safety and activity of alpelisib (a PI3Kα isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC. METHODS: Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6 mg/kg every 3 weeks. The dose-limiting toxicity (DLT), maximum tolerated dose (MTD), adverse events, overall response rate (ORR), and clinical benefit rate (CBR = CR + PR + SD > 6 months) were assessed with descriptive statistics. Progression-free survival (PFS) was calculated by the Kaplan-Meier method. RESULTS: Seventeen patients were enrolled with a median of 3 prior therapies for metastatic disease. The DLT was a maculopapular rash and MTD was 250 mg alpelisib daily. The most frequently occurring toxicities included fatigue, rash, gastrointestinal side effects, thrombocytopenia, anemia, elevated liver enzymes, and hyperglycemia. Fourteen patients were evaluable for response with an ORR of 43%. In patients with prior treatment and progression on T-DM1 (n = 10), the ORR was 30%. The CBR was 71% in evaluable patients and 60% in those with prior T-DM1. The median PFS was 8.1 months. CONCLUSIONS: The combination of alpelisib and T-DM1 is tolerable and demonstrates activity in trastuzumab-resistant HER2-positive MBC. Furthermore, activity was observed in T-DM1-resistant disease. These data suggest that PIK3CA inhibition targets an important resistance pathway to anti-HER2 therapy, providing rationale for further study of PI3K inhibition in refractory HER2-positive MBC to validate these results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Ado-Trastuzumab Emtansina , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Dose Máxima Tolerável , Maitansina/administração & dosagem , Maitansina/análogos & derivados , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Retratamento , Taxoides/administração & dosagem , Tiazóis/administração & dosagem , Trastuzumab/administração & dosagem , Resultado do Tratamento
9.
Pediatr Nephrol ; 33(4): 697-704, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29214443

RESUMO

BACKGROUND: In pediatric chronic kidney disease (pCKD), traditional factors (proteinuria, etiology, and race) do not fully explain disease progression. The levels of methylated arginine derivatives (MADs: asymmetric and symmetric dimethylarginine, respectively) rise in CKD and increase with CKD progression. The impact of MADs on glomerular filtration rate (GFR) decline has not been examined in pCKD. The aim of this study was to examine the additive impact of baseline (BL) levels of MADs on directly measured GFR (mGFR) decline per year (ml/min/1.73 m2/year) for a period of up to 4 years. METHODS: Plasma and data, including mGFR by plasma iohexol clearance, were provided by the prospective, observational Chronic Kidney Disease in Children study. BL MADs were analyzed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: For 352 pCKD subjects, the median [interquartile range] BL mGFR was 45 [35, 57] ml/min/1.73 m2. The levels of BL MADs were inversely related to the initial mGFR and its decline over time (p < 0.0005) but not to the rate of decline. Covariates, non-glomerulopathy and Tanner stage of ≥ 3 demonstrated weaker relationships between BL levels and beginning mGFR (p = 0.004 and p = 0.002, respectively). CONCLUSIONS: In pCKD, higher concentrations of BL MADs were inversely related to BL mGFR. MADs did not affect the CKD progression rate. Quantification of this relationship is novel to the pCKD literature.


Assuntos
Arginina/análogos & derivados , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Adolescente , Arginina/sangue , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Progressão da Doença , Feminino , Humanos , Lactente , Rim/fisiopatologia , Masculino , Espectrometria de Massas/métodos , Estudos Prospectivos
10.
Am J Perinatol ; 35(14): 1429-1432, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29920639

RESUMO

OBJECTIVE: Previous studies have shown that risk of cesarean section increases among multiparous women as interbirth interval increases. One possibility is that progress of labor may vary with interbirth interval, such that with longer intervals, labor curves of multiparas more closely resemble those of nulliparas. We sought to define labor curves among a cohort of multiparas with varying interbirth intervals. STUDY DESIGN: This was a retrospective cohort study of term multiparas with known interval from last delivery and only vaginal deliveries. Subjects were grouped by interval between the studied pregnancy and the most recent birth: 0 to 59, 60 to 119, and ≥120 months. Statistical analysis was performed using linear mixed effects model. Group slopes and intercepts were compared using model t-tests for individual effects. Length of second stage was compared using a Wilcoxon's rank-sum test. RESULTS: Groups did not differ significantly in demographic or obstetrical characteristics. Rate of dilation was similar between the 0 to 59 and 60 to 119 month groups (p = 0.38), but faster in the ≥120 month group compared with the 60 to 119 month group (p = 0.037). Median duration of second stage increased slightly with increased interbirth interval (p = 0.003). CONCLUSION: Prolonged interbirth interval is not associated with slower active phase of labor.


Assuntos
Intervalo entre Nascimentos , Distocia/diagnóstico , Segunda Fase do Trabalho de Parto/fisiologia , Paridade , Adulto , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Tempo
11.
Cancer ; 123(22): 4372-4381, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28727137

RESUMO

BACKGROUND: The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. METHODS: The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. RESULTS: In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). CONCLUSIONS: Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Garantia da Qualidade dos Cuidados de Saúde/métodos , Indicadores de Qualidade em Assistência à Saúde/normas , Adulto , Idoso , Terapia Combinada , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Estudos Interdisciplinares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
12.
Gastroenterology ; 151(6): 1155-1163.e2, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27575820

RESUMO

BACKGROUND & AIMS: Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. METHODS: From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. RESULTS: Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99). CONCLUSIONS: In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Radioisótopos de Ítrio/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Quimioembolização Terapêutica/efeitos adversos , Diarreia/etiologia , Progressão da Doença , Intervalo Livre de Doença , Óleo Etiodado/uso terapêutico , Feminino , Humanos , Hipoalbuminemia/etiologia , Análise de Intenção de Tratamento , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Necrose , Estadiamento de Neoplasias , Estudos Prospectivos , Taxa de Sobrevida , Radioisótopos de Ítrio/efeitos adversos
13.
PLoS Pathog ; 11(3): e1004729, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25748093

RESUMO

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 µm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.


Assuntos
Células Epiteliais/virologia , Prepúcio do Pênis/virologia , Infecções por HIV/imunologia , Infecções por HIV/transmissão , Animais , Cadáver , Circuncisão Masculina , Células Epiteliais/imunologia , Feminino , Prepúcio do Pênis/imunologia , HIV-1 , Humanos , Imuno-Histoquímica , Macaca mulatta , Masculino , Pênis/imunologia , Pênis/virologia
14.
Ann Neurol ; 79(3): 496-501, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26600088

RESUMO

We aimed to determine whether (18) F-florbetapir amyloid positron emission tomography imaging shows a clinically concordant, left-hemisphere-dominant pattern of deposition in primary progressive aphasia (PPA). Elevated cortical amyloid (Aß(+) ) was found in 19 of 32 PPA patients. Hemispheric laterality of amyloid burden was compared between Aß(+) PPA and an Aß(+) amnestic dementia groups (n = 22). The parietal region showed significantly greater left lateralized amyloid uptake in the PPA group than the amnestic group (p < 0.007), consistent with the left lateralized pattern of neurodegeneration in PPA. These results suggest that the cortical distribution of amyloid may have a greater clinical concordance than previously reported.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Afasia Primária Progressiva/metabolismo , Córtex Cerebral/metabolismo , Dominância Cerebral , Imagem Molecular/métodos , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/farmacocinética , Etilenoglicóis/farmacocinética , Coração , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
15.
J Natl Compr Canc Netw ; 15(1): 38-44, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28040718

RESUMO

BACKGROUND: The "shared-care model" for patients with cancer involves care coordination between primary care providers (PCPs) and oncologists, with the goal of optimizing survivorship care. However, a high proportion of adolescent and young adult (AYA) cancer survivors do not have a PCP. Study objectives were to increase the percentage of AYAs with a PCP documented in the electronic medical record (EMR) via the use of a best practice advisory (BPA) or "stopgap" intervention; to increase communication between providers by the number of routed clinic notes; and to assess oncology providers' attitudes/beliefs about the model and intervention. METHODS: Data were collected for the 6 months before implementation of the BPA to determine the percentage of AYAs with a PCP and the number of notes routed to providers (time point 1 [T1]). The same data were collected at time point 2 (T2) after the BPA had been implemented for 6 months. Oncology providers participated in an education video module and an online survey at T1 and a survey at T2. RESULTS: At T1, 47.1% of 756 AYAs had a documented PCP in the EMR. At T2, the percentage increased to 55.1% (P<.002). The number of routed notes did not change significantly from T1 to T2. Providers that completed the intervention survey agreed/strongly agreed that the shared-care model is a desirable model of care (T1 = 86%; T2 = 93%) and that a BPA is useful for facilitating PCP referrals (T1 = 76%; T2 = 39%). CONCLUSIONS: This BPA is feasible for increasing the percentage of AYAs with a PCP documented in the EMR and could potentially lead to increased PCP referral and communication among providers for the benefit of long-term survivorship care. Providers generally agree with the shared-care model; however, the BPA implementation requires modification.


Assuntos
Clínicos Gerais/psicologia , Comunicação Interdisciplinar , Neoplasias/terapia , Oncologistas/psicologia , Atenção Primária à Saúde/normas , Adolescente , Adulto , Registros Eletrônicos de Saúde , Feminino , Humanos , Neoplasias/mortalidade , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/métodos , Encaminhamento e Consulta , Inquéritos e Questionários , Taxa de Sobrevida , Sobreviventes , Adulto Jovem
16.
J Community Health ; 42(4): 826-838, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28332066

RESUMO

Overweight and obesity are associated with significant health problems and rates of obesity are high among Latino men. This paper describes the design, rationale and participant characteristics of the key demographic variables assessed in an NIH-funded study (R21-CA143636) addressing culture and several obesity-related variables (diet, physical activity, and body image) among Mexican and Puerto Rican men using a community-based participatory research framework. Participants completed objective measures (height, weight, body fat, hip, waist), a health and culture interview, a diet questionnaire, and used an accelerometer to measure their level of physical activity. A total of 203 participants completed the measures and the health and culture interview and 193 completed all study components. Puerto Ricans were older than Mexicans (p < .0001) and there were significant differences in marital status (p < .05), country of birth (p < .05), smoking (p < .05) and work status (p < .001). There were no significant differences in religion, education, health insurance, Body Mass Index, body fat, hip and waist measurements, and the language preference of the interview. Results have implications for the development of a future intervention that incorporates the role of cultural factors into a community participatory obesity intervention for Latino men.


Assuntos
Comportamentos Relacionados com a Saúde/etnologia , Hispânico ou Latino/estatística & dados numéricos , Obesidade/etnologia , Aculturação , Adulto , Imagem Corporal , Índice de Massa Corporal , Pesos e Medidas Corporais , Pesquisa Participativa Baseada na Comunidade , Dieta , Exercício Físico , Humanos , Masculino , Saúde do Homem , México/etnologia , Pessoa de Meia-Idade , Sobrepeso/etnologia , Porto Rico/etnologia , Projetos de Pesquisa , Fumar/etnologia , Fatores Socioeconômicos , Estresse Psicológico/etnologia , Estados Unidos/epidemiologia
17.
Pediatr Dermatol ; 34(4): 433-437, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28508417

RESUMO

BACKGROUND/OBJECTIVES: Epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) includes immune-mediated, life-threatening inflammatory blistering disorders that can affect children. The Score of Toxic Epidermal Necrosis (SCORTEN) tool has accurately predicted the outcome of these disorders in adults but has not been tested in children. METHODS: We performed a retrospective chart review to compare the accuracy of the adult SCORTEN tool with that of two modifications tailored to children in predicting disease outcome. RESULTS: The longer the patient's median length of hospital stay was, the higher the adult and two proposed pediatric SCORTENs were. In addition, all patients who died had SCORTENs greater than 4. CONCLUSION: The pediatric-modified tools were not superior to the adult SCORTEN, which accurately predicted outcome.


Assuntos
Síndrome de Stevens-Johnson/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
18.
Alzheimers Dement ; 13(12): 1337-1344, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28586648

RESUMO

INTRODUCTION: Functional and cognitive features of subjective cognitive decline (SCD) were identified in a longitudinal database from the National Alzheimer's Coordinating Center. METHODS: Cognitively normal older adults with (SCD+) and without (SCD-) self-reported memory complaints (N = 3915) were compared on (1) baseline Functional Assessment Questionnaire ratings, (2) baseline scores and longitudinal rate of change estimates from nine neuropsychological tests, and (3) final clinical diagnoses. RESULTS: SCD+ had higher baseline ratings of functional impairment, reduced episodic memory practice effects and poorer performance on neuropsychological tests of psychomotor speed and language, and higher frequencies of mild cognitive impairment and dementia diagnoses at the end of follow-up compared with the SCD-group. DISCUSSION: Subtle clinical features of SCD identified in this large cohort are difficult to detect at the individual level. More sensitive tests are needed to identify those with SCD who are vulnerable to cognitive decline and dementia.


Assuntos
Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Transtornos Cognitivos/genética , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Psicometria , Estados Unidos/epidemiologia
19.
J Neurosci ; 35(4): 1781-91, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25632151

RESUMO

This human study is based on an established cohort of "SuperAgers," 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20-30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50-60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age.


Assuntos
Envelhecimento , Mapeamento Encefálico , Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/fisiologia , Memória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Estudos de Casos e Controles , Tamanho Celular , Feminino , Genótipo , Giro do Cíngulo/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/patologia , Neurônios/patologia , Mudanças Depois da Morte
20.
Crit Care Med ; 44(8): 1515-22, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27035237

RESUMO

OBJECTIVE: Low tidal volume ventilation lowers mortality in the acute respiratory distress syndrome. Previous studies reported poor low tidal volume ventilation implementation. We sought to determine the rate, quality, and predictors of low tidal volume ventilation use. DESIGN: Retrospective cross-sectional study. SETTING: One academic and three community hospitals in the Chicago region. PATIENTS: A total of 362 adults meeting the Berlin Definition of acute respiratory distress syndrome consecutively admitted between June and December 2013. MEASUREMENTS AND MAIN RESULTS: Seventy patients (19.3%) were treated with low tidal volume ventilation (tidal volume < 6.5 mL/kg predicted body weight) at some time during mechanical ventilation. In total, 22.2% of patients requiring an FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and plateau pressure greater than 30 cm H2O received low tidal volume ventilation. The entire cohort received low tidal volume ventilation 11.4% of the time patients had acute respiratory distress syndrome. Among patients who received low tidal volume ventilation, the mean (SD) percentage of acute respiratory distress syndrome time it was used was 59.1% (38.2%), and 34% waited more than 72 hours prior to low tidal volume ventilation initiation. Women were less likely to receive low tidal volume ventilation, whereas sepsis and FIO2 greater than 40% were associated with increased odds of low tidal volume ventilation use. Four attending physicians (6.2%) initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset for greater than or equal to 50% of their patients, whereas 34 physicians (52.3%) never initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset. In total, 54.4% of patients received a tidal volume less than 8 mL/kg predicted body weight, and the mean tidal volume during the first 72 hours after acute respiratory distress syndrome onset was never less than 8 mL/kg predicted body weight. CONCLUSIONS: More than 12 years after publication of the landmark low tidal volume ventilation study, use remains poor. Interventions that improve adoption of low tidal volume ventilation are needed.


Assuntos
Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Volume de Ventilação Pulmonar , Adulto , Idoso , Peso Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Sepse/complicações , Índice de Gravidade de Doença , Fatores Sexuais
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