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[PMID]:29362794
[Au] Autor:Friedman DJ; Piccini JP; Wang T; Zheng J; Malaisrie SC; Holmes DR; Suri RM; Mack MJ; Badhwar V; Jacobs JP; Gaca JG; Chow SC; Peterson ED; Brennan JM
[Ad] Endereço:Duke Clinical Research Institute, Durham, North Carolina.
[Ti] Título:Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery.
[So] Source:JAMA;319(4):365-374, 2018 01 23.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: The left atrial appendage is a key site of thrombus formation in atrial fibrillation (AF) and can be occluded or removed at the time of cardiac surgery. There is limited evidence regarding the effectiveness of surgical left atrial appendage occlusion (S-LAAO) for reducing the risk of thromboembolism. Objective: To evaluate the association of S-LAAO vs no receipt of S-LAAO with the risk of thromboembolism among older patients undergoing cardiac surgery. Design, Setting, and Participants: Retrospective cohort study of a nationally representative Medicare-linked cohort from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2012). Patients aged 65 years and older with AF undergoing cardiac surgery (coronary artery bypass grafting [CABG], mitral valve surgery with or without CABG, or aortic valve surgery with or without CABG) with and without concomitant S-LAAO were followed up until December 31, 2014. Exposures: S-LAAO vs no S-LAAO. Main Outcomes and Measures: The primary outcome was readmission for thromboembolism (stroke, transient ischemic attack, or systemic embolism) at up to 3 years of follow-up, as defined by Medicare claims data. Secondary end points included hemorrhagic stroke, all-cause mortality, and a composite end point (thromboembolism, hemorrhagic stroke, or all-cause mortality). Results: Among 10 524 patients undergoing surgery (median age, 76 years; 39% female; median CHA2DS2-VASc score, 4), 3892 (37%) underwent S-LAAO. Overall, at a mean follow-up of 2.6 years, thromboembolism occurred in 5.4%, hemorrhagic stroke in 0.9%, all-cause mortality in 21.5%, and the composite end point in 25.7%. S-LAAO, compared with no S-LAAO, was associated with lower unadjusted rates of thromboembolism (4.2% vs 6.2%), all-cause mortality (17.3% vs 23.9%), and the composite end point (20.5% vs 28.7%) but no significant difference in rates of hemorrhagic stroke (0.9% vs 0.9%). After inverse probability-weighted adjustment, S-LAAO was associated with a significantly lower rate of thromboembolism (subdistribution hazard ratio [HR], 0.67; 95% CI, 0.56-0.81; P < .001), all-cause mortality (HR, 0.88; 95% CI, 0.79-0.97; P = .001), and the composite end point (HR, 0.83; 95% CI, 0.76-0.91; P < .001) but not hemorrhagic stroke (subdistribution HR, 0.84; 95% CI, 0.53-1.32; P = .44). S-LAAO, compared with no S-LAAO, was associated with a lower risk of thromboembolism among patients discharged without anticoagulation (unadjusted rate, 4.2% vs 6.0%; adjusted subdistribution HR, 0.26; 95% CI, 0.17-0.40; P < .001), but not among patients discharged with anticoagulation (unadjusted rate, 4.1% vs 6.3%; adjusted subdistribution HR, 0.88; 95% CI, 0.56-1.39; P = .59). Conclusions and Relevance: Among older patients with AF undergoing concomitant cardiac surgery, S-LAAO, compared with no S-LAAO, was associated with a lower risk of readmission for thromboembolism over 3 years. These findings support the use of S-LAAO, but randomized trials are necessary to provide definitive evidence.
[Mh] Termos MeSH primário: Apêndice Atrial/cirurgia
Fibrilação Atrial
Procedimentos Cirúrgicos Cardíacos/efeitos adversos
Readmissão do Paciente/estatística & dados numéricos
Tromboembolia/prevenção & controle
[Mh] Termos MeSH secundário: Idoso
Valva Aórtica/cirurgia
Ponte de Artéria Coronária/efeitos adversos
Seguimentos
Seres Humanos
Estimativa de Kaplan-Meier
Valva Mitral/cirurgia
Modelos de Riscos Proporcionais
Estudos Retrospectivos
Dispositivo para Oclusão Septal
Tromboembolia/epidemiologia
Tromboembolia/etiologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20125


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[PMID]:29340677
[Au] Autor:Reges O; Greenland P; Dicker D; Leibowitz M; Hoshen M; Gofer I; Rasmussen-Torvik LJ; Balicer RD
[Ad] Endereço:Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel.
[Ti] Título:Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With All-Cause Mortality.
[So] Source:JAMA;319(3):279-290, 2018 01 16.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Bariatric surgery is an effective and safe approach for weight loss and short-term improvement in metabolic disorders such as diabetes. However, studies have been limited in most settings by lack of a nonsurgical group, losses to follow-up, missing data, and small sample sizes in clinical trials and observational studies. Objective: To assess the association of 3 common types of bariatric surgery compared with nonsurgical treatment with mortality and other clinical outcomes among obese patients. Design, Setting, and Participants: Retrospective cohort study in a large Israeli integrated health fund covering 54% of Israeli citizens with less than 1% turnover of members annually. Obese adult patients who underwent bariatric surgery between January 1, 2005, and December 31, 2014, were selected and compared with obese nonsurgical patients matched on age, sex, body mass index (BMI), and diabetes, with a final follow-up date of December 31, 2015. A total of 33 540 patients were included in this study. Exposures: Bariatric surgery (laparoscopic banding, Roux-en-Y gastric bypass, or laparoscopic sleeve gastrectomy) or usual care obesity management only (provided by a primary care physician and which may include dietary counseling and behavior modification). Main Outcomes and Measures: The primary outcome, all-cause mortality, matched and adjusted for BMI prior to surgery, age, sex, socioeconomic status, diabetes, hyperlipidemia, hypertension, cardiovascular disease, and smoking. Results: The study population included 8385 patients who underwent bariatric surgery (median age, 46 [IQR, 37-54] years; 5490 [65.5%] women; baseline median BMI, 40.6 [IQR, 38.5-43.7]; laparoscopic banding [n = 3635], gastric bypass [n = 1388], laparoscopic sleeve gastrectomy [n = 3362], and 25 155 nonsurgical matched patients (median age, 46 [IQR, 37-54] years; 16 470 [65.5%] women; baseline median BMI, 40.5 [IQR, 37.0-43.5]). The availability of follow-up data was 100% for all-cause mortality. There were 105 deaths (1.3%) among surgical patients during a median follow-up of 4.3 (IQR, 2.8-6.6) years (including 61 [1.7%] who underwent laparoscopic banding, 18 [1.3%] gastric bypass, and 26 [0.8%] sleeve gastrectomy), and 583 deaths (2.3%) among nonsurgical patients during a median follow-up of 4.0 (IQR, 2.6-6.2) years. The absolute difference was 2.51 (95% CI, 1.86-3.15) fewer deaths/1000 person-years in the surgical vs nonsurgical group. Adjusted hazard ratios (HRs) for mortality among nonsurgical vs surgical patients were 2.02 (95% CI, 1.63-2.52) for the entire study population; by surgical type, HRs were 2.01 (95% CI, 1.50-2.69) for laparoscopic banding, 2.65 (95% CI, 1.55-4.52) for gastric bypass, and 1.60 (95% CI, 1.02-2.51) for laparoscopic sleeve gastrectomy. Conclusions and Relevance: Among obese patients in a large integrated health fund in Israel, bariatric surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve gastrectomy, compared with usual care nonsurgical obesity management, was associated with lower all-cause mortality over a median follow-up of approximately 4.5 years. The evidence of this association adds to the limited literature describing beneficial outcomes of these 3 types of bariatric surgery compared with usual care obesity management alone.
[Mh] Termos MeSH primário: Gastrectomia/mortalidade
Derivação Gástrica/mortalidade
Gastroplastia/mortalidade
Laparoscopia
Obesidade Mórbida/mortalidade
Obesidade Mórbida/terapia
[Mh] Termos MeSH secundário: Adulto
Feminino
Gastrectomia/métodos
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Obesidade Mórbida/cirurgia
Modelos de Riscos Proporcionais
Estudos Retrospectivos
Perda de Peso
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20513


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[PMID]:29408862
[Au] Autor:Hoffmann S; Laurier D; Rage E; Guihenneuc C; Ancelet S
[Ad] Endereço:Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France.
[Ti] Título:Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models.
[So] Source:PLoS One;13(2):e0190792, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Exposure measurement error represents one of the most important sources of uncertainty in epidemiology. When exposure uncertainty is not or only poorly accounted for, it can lead to biased risk estimates and a distortion of the shape of the exposure-response relationship. In occupational cohort studies, the time-dependent nature of exposure and changes in the method of exposure assessment may create complex error structures. When a method of group-level exposure assessment is used, individual worker practices and the imprecision of the instrument used to measure the average exposure for a group of workers may give rise to errors that are shared between workers, within workers or both. In contrast to unshared measurement error, the effects of shared errors remain largely unknown. Moreover, exposure uncertainty and magnitude of exposure are typically highest for the earliest years of exposure. We conduct a simulation study based on exposure data of the French cohort of uranium miners to compare the effects of shared and unshared exposure uncertainty on risk estimation and on the shape of the exposure-response curve in proportional hazards models. Our results indicate that uncertainty components shared within workers cause more bias in risk estimation and a more severe attenuation of the exposure-response relationship than unshared exposure uncertainty or exposure uncertainty shared between individuals. These findings underline the importance of careful characterisation and modeling of exposure uncertainty in observational studies.
[Mh] Termos MeSH primário: Exposição Ambiental
Modelos de Riscos Proporcionais
[Mh] Termos MeSH secundário: Estudos de Coortes
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190792


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[PMID]:28464839
[Au] Autor:Pavlic K; Perme MP
[Ad] Endereço:University of Ljubljana, Faculty of Medicine, Institute for Biostatistics and Medical Informatics, Vrazov trg 2, Ljubljana, 1000, Slovenia.
[Ti] Título:On comparison of net survival curves.
[So] Source:BMC Med Res Methodol;17(1):79, 2017 May 02.
[Is] ISSN:1471-2288
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Relative survival analysis is a subfield of survival analysis where competing risks data are observed, but the causes of death are unknown. A first step in the analysis of such data is usually the estimation of a net survival curve, possibly followed by regression modelling. Recently, a log-rank type test for comparison of net survival curves has been introduced and the goal of this paper is to explore its properties and put this methodological advance into the context of the field. METHODS: We build on the association between the log-rank test and the univariate or stratified Cox model and show the analogy in the relative survival setting. We study the properties of the methods using both the theoretical arguments as well as simulations. We provide an R function to enable practical usage of the log-rank type test. RESULTS: Both the log-rank type test and its model alternatives perform satisfactory under the null, even if the correlation between their p-values is rather low, implying that both approaches cannot be used simultaneously. The stratified version has a higher power in case of non-homogeneous hazards, but also carries a different interpretation. CONCLUSIONS: The log-rank type test and its stratified version can be interpreted in the same way as the results of an analogous semi-parametric additive regression model despite the fact that no direct theoretical link can be established between the test statistics.
[Mh] Termos MeSH primário: Infarto do Miocárdio/mortalidade
[Mh] Termos MeSH secundário: Fatores Etários
Idoso
Simulação por Computador
Interpretação Estatística de Dados
Feminino
Seres Humanos
Masculino
Meia-Idade
Modelos de Riscos Proporcionais
Análise de Regressão
Risco
Fatores Sexuais
Análise de Sobrevida
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1186/s12874-017-0351-3


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[PMID]:28453767
[Au] Autor:Chu TPC; Moran GW; Card TR
[Ad] Endereço:Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
[Ti] Título:The Pattern of Underlying Cause of Death in Patients with Inflammatory Bowel Disease in England: A Record Linkage Study.
[So] Source:J Crohns Colitis;11(5):578-585, 2017 May 01.
[Is] ISSN:1876-4479
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background and Aims: Numerous studies have established that mortality risk in inflammatory bowel disease [IBD] patients is higher than in the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD. Methods: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models. Results: 20293 IBD patients were matched to 83261 non IBD patients. The mortality rate was 40% higher in IBD patients [2005 deaths] than in non IBD patients [6024 deaths] (adjusted overall hazard ratio: = 1.4, 95% confidence interval [CI]: = 1.4-1.5], with greater risk of death in Crohn's disease [hazard ratio: = 1.6, 1.5-1.7] than in ulcerative colitis [1.3, 1.3-1.4]. Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn's disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than among non IBD patients. In both IBD and non IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer rather than gastrointestinal cancers. Conclusions: IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD is clinically less important.
[Mh] Termos MeSH primário: Causas de Morte
Doenças Inflamatórias Intestinais/mortalidade
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Idoso
Idoso de 80 Anos ou mais
Criança
Pré-Escolar
Colite Ulcerativa/mortalidade
Doença de Crohn/mortalidade
Atestado de Óbito
Feminino
Seres Humanos
Lactente
Recém-Nascido
Armazenamento e Recuperação da Informação
Masculino
Registros Médicos/estatística & dados numéricos
Meia-Idade
Modelos de Riscos Proporcionais
Reino Unido/epidemiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/ecco-jcc/jjw192


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[PMID]:28453695
[Au] Autor:Suenaga M; Schirripa M; Cao S; Zhang W; Yang D; Murgioni S; Rossini D; Marmorino F; Mennitto A; Ning Y; Okazaki S; Berger MD; Miyamoto Y; Gopez R; Barzi A; Yamaguchi T; Loupakis F; Lenz HJ
[Ad] Endereço:Department of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
[Ti] Título:Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.
[So] Source:Ann Oncol;28(5):1015-1022, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias Colorretais/genética
Enzimas Reparadoras do DNA/genética
Neoplasias Hepáticas/genética
Trifluridina/uso terapêutico
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/farmacologia
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Intervalo Livre de Doença
Combinação de Medicamentos
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Estudos de Associação Genética
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Compostos de Fenilureia/farmacologia
Compostos de Fenilureia/uso terapêutico
Modelos de Riscos Proporcionais
Piridinas/farmacologia
Piridinas/uso terapêutico
Estudos Retrospectivos
Resultado do Tratamento
Trifluridina/farmacologia
Uracila/farmacologia
Uracila/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (Phenylurea Compounds); 0 (Pyridines); 0 (TAS 102); 24T2A1DOYB (regorafenib); 56HH86ZVCT (Uracil); EC 6.5.1.- (DNA Repair Enzymes); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx035


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[PMID]:28922784
[Au] Autor:Jiao L; Chen L; White DL; Tinker L; Chlebowski RT; Van Horn LV; Richardson P; Lane D; Sangi-Haghpeykar H; El-Serag HB
[Ad] Endereço:Department of Medicine, Department of Obstetrics and Gynecology, and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX; Division of Public Health Sciences, Fred
[Ti] Título:Low-fat Dietary Pattern and Pancreatic Cancer Risk in the Women's Health Initiative Dietary Modification Randomized Controlled Trial.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Observational studies suggest that diet may influence pancreatic cancer risk. We investigated the effect of a low-fat dietary intervention on pancreatic cancer incidence. Methods: The Women's Health Initiative Dietary Modification (WHI-DM) trial is a randomized controlled trial conducted in 48 835 postmenopausal women age 50 to 79 years in the United States between 1993 and 1998. Women were randomly assigned to the intervention group (n = 19 541), with the goal of reducing total fat intake and increasing intake of vegetables, fruits, and grains, or to the usual diet comparison group (n = 29 294). The intervention concluded in March 2005. We evaluated the effect of the intervention on pancreatic cancer incidence with the follow-up through 2014 using the log-rank test and multivariable Cox proportional hazards regression model. All statistical tests were two-sided. Results: In intention-to-treat analyses including 46 200 women, 92 vs 165 pancreatic cancer cases were ascertained in the intervention vs the comparison group (P = .23). The multivariable hazard ratio (HR) of pancreatic cancer was 0.86 (95% confidence interval [CI] = 0.67 to 1.11). Risk was statistically significantly reduced among women with baseline body mass indexes (BMIs) of 25 kg/m2 or higher (HR = 0.71, 95% CI = 0.53 to 0.96), but not among women with BMIs of less than 25 kg/m2 (HR = 1.62, 95% CI = 0.97 to 2.71, Pinteraction = .01). Conclusions: A low-fat dietary intervention was associated with reduced pancreatic cancer incidence in women who were overweight or obese in the WHI-DM trial. Caution needs to be taken in interpreting the findings based on subgroup analyses.
[Mh] Termos MeSH primário: Índice de Massa Corporal
Dieta com Restrição de Gorduras
Neoplasias Pancreáticas/epidemiologia
Neoplasias Pancreáticas/prevenção & controle
[Mh] Termos MeSH secundário: Idoso
Grãos Comestíveis
Feminino
Seguimentos
Frutas
Seres Humanos
Análise de Intenção de Tratamento
Meia-Idade
Obesidade/epidemiologia
Modelos de Riscos Proporcionais
Fatores de Proteção
Estados Unidos
Verduras
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx117


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[PMID]:28453848
[Au] Autor:Kakiuchi S; Tsuji M; Nishimura H; Yoshikawa T; Wang L; Takayama-Ito M; Kinoshita H; Lim CK; Fujii H; Yamada S; Harada S; Oka A; Mizuguchi M; Taniguchi S; Saijo M
[Ad] Endereço:Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan.
[Ti] Título:Association of the Emergence of Acyclovir-Resistant Herpes Simplex Virus Type 1 With Prognosis in Hematopoietic Stem Cell Transplantation Patients.
[So] Source:J Infect Dis;215(6):865-873, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Antiviral-resistant herpes simplex virus type 1 (HSV-1) has been recognized as an emerging clinical problem among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods: A prospective observational study was conducted at a hematological center over a 2-year period. Oropharyngeal swab samples were serially collected each week from 1 week before and up to 100 days after HSCT and were tested for virus isolation. The HSV-1 isolates were tested for sensitivity to acyclovir (ACV). The prognosis of patients with ACV-resistant (ACVr) HSV-1 and the genetic background of the ACVr HSV-1 isolates were assessed. Results: Herpes simplex virus type 1 was isolated in 39 of 268 (15%) HSCT patients within 100 days after transplantation. Acyclovir-resistant HSV-1 emerged in 11 of these 39 patients (28%). The 100-day death rates of HSCT patients without HSV-1 shedding, those with only ACV-sensitive HSV-1 shedding, and those with ACVr HSV-1 shedding were 31%, 39%, and 64%, respectively. Patients with HSV-1, including ACVr HSV-1, shedding showed a significantly higher mortality rate. Relapsed malignancies were a significant risk factor for the emergence of ACVr HSV-1. Acyclovir resistance was attributable to viral thymidine kinase and DNA polymerase mutations in 6 and 5 patients, respectively. Conclusions: Herpes simplex virus type 1, including ACVr HSV-1, shedding was associated with poorer outcome in HSCT patients, even if HSV disease did not always occur. Patients with relapsed malignancies were at especially high risk for the emergence of ACVr HSV-1.
[Mh] Termos MeSH primário: Aciclovir/uso terapêutico
Antivirais/uso terapêutico
Farmacorresistência Viral
Transplante de Células-Tronco Hematopoéticas/mortalidade
Herpes Simples/tratamento farmacológico
Herpesvirus Humano 1/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
DNA Polimerase Dirigida por DNA/genética
Feminino
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Herpes Simples/virologia
Herpesvirus Humano 1/isolamento & purificação
Seres Humanos
Japão
Masculino
Testes de Sensibilidade Microbiana
Meia-Idade
Análise Multivariada
Complicações Pós-Operatórias/virologia
Prognóstico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Recidiva
Taxa de Sobrevida
Timidina Quinase/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antiviral Agents); EC 2.7.1.21 (Thymidine Kinase); EC 2.7.7.7 (DNA-Directed DNA Polymerase); X4HES1O11F (Acyclovir)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix042


  9 / 63417 MEDLINE  
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[PMID]:28453835
[Au] Autor:Celum C; Hong T; Cent A; Donnell D; Morrow R; Baeten JM; Firnhaber C; Grinsztejn B; Hosseinipour MC; Lalloo U; Nyirenda M; Riviere C; Sanchez J; Santos B; Supparatpinyo K; Hakim J; Kumarasamy N; Campbell TB; ACTG PEARLS/A5175 Team
[Ad] Endereço:Department of Global Health, University of Washington , Seattle, Washington, USA.
[Ti] Título:Herpes Simplex Virus Type 2 Acquisition Among HIV-1-Infected Adults Treated With Tenofovir Disoproxyl Fumarate as Part of Combination Antiretroviral Therapy: Results From the ACTG A5175 PEARLS Study.
[So] Source:J Infect Dis;215(6):907-910, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Objective: Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2 acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design: Secondary analysis of AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART regimens among 1571 participants. Methods: HSV-2 serostatus was assessed at baseline, at study exit, and before a change in ART regimen. Results: Of 365 HSV-2-seronegative persons, 68 acquired HSV-2, with 24 receiving TDF-containing ART and 44 receiving ART without TDF (HSV-2 seroconversion incidence, 6.42 and 6.63 cases/100 person-years, respectively; hazard ratio, 0.89; 95% confidence interval, .55-1.44). Conclusions: HSV-2 acquisition was not reduced in HIV-infected, HSV-2-uninfected persons during TDF-containing ART.
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Infecções por HIV/complicações
Herpes Simples/prevenção & controle
Herpesvirus Humano 2/efeitos dos fármacos
Profilaxia Pré-Exposição
Tenofovir/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Feminino
Infecções por HIV/tratamento farmacológico
HIV-1/efeitos dos fármacos
Seres Humanos
Cooperação Internacional
Masculino
Adesão à Medicação
Meia-Idade
Modelos de Riscos Proporcionais
Soroconversão
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antiviral Agents); 99YXE507IL (Tenofovir)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix029


  10 / 63417 MEDLINE  
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[PMID]:28453705
[Au] Autor:Mato AR; Hill BT; Lamanna N; Barr PM; Ujjani CS; Brander DM; Howlett C; Skarbnik AP; Cheson BD; Zent CS; Pu JJ; Kiselev P; Foon K; Lenhart J; Henick Bachow S; Winter AM; Cruz AL; Claxton DF; Goy A; Daniel C; Isaac K; Kennard KH; Timlin C; Fanning M; Gashonia L; Yacur M; Svoboda J; Schuster SJ; Nabhan C
[Ad] Endereço:Center for CLL, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.
[Ti] Título:Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients.
[So] Source:Ann Oncol;28(5):1050-1056, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results: A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions: In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem
Intervalo Livre de Doença
Esquema de Medicação
Seres Humanos
Estimativa de Kaplan-Meier
Leucemia Linfocítica Crônica de Células B/mortalidade
Meia-Idade
Modelos de Riscos Proporcionais
Purinas/administração & dosagem
Pirazóis/administração & dosagem
Pirimidinas/administração & dosagem
Quinazolinonas/administração & dosagem
Estudos Retrospectivos
Sulfonamidas/administração & dosagem
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (PCI 32765); 0 (Purines); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Quinazolinones); 0 (Sulfonamides); N54AIC43PW (venetoclax); YG57I8T5M0 (idelalisib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx031



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