An Incident Cohort Study Comparing Survival on Home Hemodialysis and Peritoneal Dialysis (Australia and New Zealand Dialysis and Transplantation Registry)

PubMed Central

Nadeau-Fredette, Annie-Claire; Hawley, Carmel M.; Pascoe, Elaine M.; Chan, Christopher T.; Clayton, Philip A.; Polkinghorne, Kevan R.; Boudville, Neil; Leblanc, Martine

2015-01-01

Background and objectives Home dialysis is often recognized as a first-choice therapy for patients initiating dialysis. However, studies comparing clinical outcomes between peritoneal dialysis and home hemodialysis have been very limited. Design, setting, participants, & measurements This Australia and New Zealand Dialysis and Transplantation Registry study assessed all Australian and New Zealand adult patients receiving home dialysis on day 90 after initiation of RRT between 2000 and 2012. The primary outcome was overall survival. The secondary outcomes were on-treatment survival, patient and technique survival, and death-censored technique survival. All results were adjusted with three prespecified models: multivariable Cox proportional hazards model (main model), propensity score quintile–stratified model, and propensity score–matched model. Results The study included 10,710 patients on incident peritoneal dialysis and 706 patients on incident home hemodialysis. Treatment with home hemodialysis was associated with better patient survival than treatment with peritoneal dialysis (5-year survival: 85% versus 44%, respectively; log-rank P<0.001). Using multivariable Cox proportional hazards analysis, home hemodialysis was associated with superior patient survival (hazard ratio for overall death, 0.47; 95% confidence interval, 0.38 to 0.59) as well as better on-treatment survival (hazard ratio for on-treatment death, 0.34; 95% confidence interval, 0.26 to 0.45), composite patient and technique survival (hazard ratio for death or technique failure, 0.34; 95% confidence interval, 0.29 to 0.40), and death-censored technique survival (hazard ratio for technique failure, 0.34; 95% confidence interval, 0.28 to 0.41). Similar results were obtained with the propensity score models as well as sensitivity analyses using competing risks models and different definitions for technique failure and lag period after modality switch, during which events were attributed to the initial modality. Conclusions Home hemodialysis was associated with superior patient and technique survival compared with peritoneal dialysis. PMID:26068181

Experiments to Determine Whether Recursive Partitioning (CART) or an Artificial Neural Network Overcomes Theoretical Limitations of Cox Proportional Hazards Regression

NASA Technical Reports Server (NTRS)

Kattan, Michael W.; Hess, Kenneth R.; Kattan, Michael W.

1998-01-01

New computationally intensive tools for medical survival analyses include recursive partitioning (also called CART) and artificial neural networks. A challenge that remains is to better understand the behavior of these techniques in effort to know when they will be effective tools. Theoretically they may overcome limitations of the traditional multivariable survival technique, the Cox proportional hazards regression model. Experiments were designed to test whether the new tools would, in practice, overcome these limitations. Two datasets in which theory suggests CART and the neural network should outperform the Cox model were selected. The first was a published leukemia dataset manipulated to have a strong interaction that CART should detect. The second was a published cirrhosis dataset with pronounced nonlinear effects that a neural network should fit. Repeated sampling of 50 training and testing subsets was applied to each technique. The concordance index C was calculated as a measure of predictive accuracy by each technique on the testing dataset. In the interaction dataset, CART outperformed Cox (P less than 0.05) with a C improvement of 0.1 (95% Cl, 0.08 to 0.12). In the nonlinear dataset, the neural network outperformed the Cox model (P less than 0.05), but by a very slight amount (0.015). As predicted by theory, CART and the neural network were able to overcome limitations of the Cox model. Experiments like these are important to increase our understanding of when one of these new techniques will outperform the standard Cox model. Further research is necessary to predict which technique will do best a priori and to assess the magnitude of superiority.

Is Genetic Background Important in Lung Cancer Survival?

PubMed Central

Lindström, Linda S.; Hall, Per; Hartman, Mikael; Wiklund, Fredrik; Czene, Kamila

2009-01-01

Background In lung cancer, a patient's survival is poor with a wide variation in survival within the stage of disease. The aim of this study was to investigate the familial concordance in lung cancer survival by means of analyses of pairs with different degrees of familial relationships. Methods Our population-based Swedish family database included three million families and over 58 100 lung cancer patients. We modelled the proband (parent, sibling, spouse) survival utilizing a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. Subsequently, the survival in proband's relative (child, sibling, spouse) was analysed with a Cox model. Findings By use of Cox modelling with 5 years follow-up, we noted a decreased hazard ratio for death in children with good parental survival (Hazard Ratio [HR] = 0.71, 95% CI = 0.51 to 0.99), compared to those with poor parental survival. Also for siblings, a very strong protective effect was seen (HR = 0.14, 95% CI = 0.030 to 0.65). Finally, in spouses no correlation in survival was found. Interpretation Our findings suggest that genetic factors are important in lung cancer survival. In a clinical setting, information on prognosis in a relative may be vital in foreseeing the survival in an individual newly diagnosed with lung cancer. Future molecular studies enhancing the understanding of the underlying mechanisms and pathways are needed. PMID:19478952

Herpes zoster correlates with increased risk of Parkinson's disease in older people

PubMed Central

Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

2017-01-01

Abstract Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease. PMID:28207515

Herpes zoster could be an early manifestation of undiagnosed human immunodeficiency virus infection.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu; Chen, Wen-Chi

2016-05-01

No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04-4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10-6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster. Copyright © 2015. Published by Elsevier B.V.

The Covariance Adjustment Approaches for Combining Incomparable Cox Regressions Caused by Unbalanced Covariates Adjustment: A Multivariate Meta-Analysis Study.

PubMed

Dehesh, Tania; Zare, Najaf; Ayatollahi, Seyyed Mohammad Taghi

2015-01-01

Univariate meta-analysis (UM) procedure, as a technique that provides a single overall result, has become increasingly popular. Neglecting the existence of other concomitant covariates in the models leads to loss of treatment efficiency. Our aim was proposing four new approximation approaches for the covariance matrix of the coefficients, which is not readily available for the multivariate generalized least square (MGLS) method as a multivariate meta-analysis approach. We evaluated the efficiency of four new approaches including zero correlation (ZC), common correlation (CC), estimated correlation (EC), and multivariate multilevel correlation (MMC) on the estimation bias, mean square error (MSE), and 95% probability coverage of the confidence interval (CI) in the synthesis of Cox proportional hazard models coefficients in a simulation study. Comparing the results of the simulation study on the MSE, bias, and CI of the estimated coefficients indicated that MMC approach was the most accurate procedure compared to EC, CC, and ZC procedures. The precision ranking of the four approaches according to all above settings was MMC ≥ EC ≥ CC ≥ ZC. This study highlights advantages of MGLS meta-analysis on UM approach. The results suggested the use of MMC procedure to overcome the lack of information for having a complete covariance matrix of the coefficients.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

PubMed Central

Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

2017-01-01

Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

PubMed

Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

2017-01-01

Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

Added prognostic value of CT characteristics and IASLC/ATS/ERS histologic subtype in surgically resected lung adenocarcinomas.

PubMed

Suh, Young Joo; Lee, Hyun-Ju; Kim, Young Tae; Kang, Chang Hyun; Park, In Kyu; Jeon, Yoon Kyung; Chung, Doo Hyun

2018-06-01

Our study investigates the added value of computed tomography (CT) characteristics, histologic subtype classification of the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS), and genetic mutation for predicting postoperative prognoses of patients who received curative surgical resections for lung adenocarcinoma. We retrospectively enrolled 988 patients who underwent curative resection for invasive lung adenocarcinoma between October 2007 and December 2013. Cox's proportional hazard model was used to explore the risk of recurrence-free survival, based on the combination of conventional prognostic factors, CT characteristics, IASLC/ATS/ERS histologic subtype, and epidermal growth factor receptor (EGFR) mutations. Incremental prognostic values of CT characteristics, histologic subtype, and EGFR mutations over conventional risk factors were measured by C-statistics. During median follow-up period of 44.7 months (25th to 75th percentile 24.6-59.7 months), postoperative recurrence occurred in 248 patients (25.1%). In univariate Cox proportion hazard model, female sex, tumor size and stage, CT characteristics, and predominant histologic subtype were associated with tumor recurrence (P < 0.05). In multivariate Cox regression model adjusted for tumor size and stage, both CT characteristics and histologic subtype were independent tumor recurrence predictors (P < 0.05). Cox proportion hazard models combining CT characteristics or histologic subtype with size and tumor stage showed higher C-indices (0.763 and 0.767, respectively) than size and stage-only models (C-index 0.759, P > 0.05). CT characteristics and histologic subtype have relatively limited added prognostic values over tumor size and stage in surgically resected lung adenocarcinomas. Copyright © 2018 Elsevier B.V. All rights reserved.

Long-term allopurinol use decreases the risk of prostate cancer in patients with gout: a population-based study.

PubMed

Shih, H-J; Kao, M-C; Tsai, P-S; Fan, Y-C; Huang, C-J

2017-09-01

Clinical observations indicated an increased risk of developing prostate cancer in gout patients. Chronic inflammation is postulated to be one crucial mechanism for prostate carcinogenesis. Allopurinol, a widely used antigout agent, possesses potent anti-inflammation capacity. We elucidated whether allopurinol decreases the risk of prostate cancer in gout patients. We analyzed data retrieved from Taiwan National Health Insurance Database between January 2000 and December 2012. Patients diagnosed with gout during the study period with no history of prostate cancer and who had never used allopurinol were selected. Four allopurinol use cohorts (that is, allopurinol use (>365 days), allopurinol use (181-365 days), allopurinol use (91-180 days) and allopurinol use (31-90 days)) and one cohort without using allopurinol (that is, allopurinol use (No)) were included. The study end point was the diagnosis of new-onset prostate cancer. Multivariable Cox proportional hazards regression and propensity score-adjusted Cox regression models were used to estimate the association between the risk of prostate cancer and allopurinol treatment in gout patients after adjusting for potential confounders. A total of 25 770 gout patients (aged between 40 and 100 years) were included. Multivariable Cox regression analyses revealed that the risk of developing prostate cancer in the allopurinol use (>365 days) cohort was significantly lower than the allopurinol use (No) cohort (adjusted hazard ratio (HR)=0.64, 95% confidence interval (CI)=0.45-0.9, P=0.011). After propensity score adjustment, the trend remained the same (adjusted HR=0.66, 95% CI=0.46-0.93, P=0.019). Long-term (more than 1 year) allopurinol use may associate with a decreased risk of prostate cancer in gout patients.

Emergence and predictors of alcohol reference displays on Facebook during the first year of college

PubMed Central

Moreno, Megan A; D’Angelo, Jonathan; Kacvinsky, Lauren E.; Kerr, Bradley; Zhang, Chong; Eickhoff, Jens

2013-01-01

The purpose of this study was to investigate the emergence of displayed alcohol references on Facebook for first-year students from two universities. Graduated high school seniors who were planning to attend one of the two targeted study universities were recruited. Participants’ Facebook profiles were evaluated for displayed alcohol references at baseline and every four weeks throughout the first year of college. Profiles were categorized as Non-Displayers, Alcohol Displayers or Intoxication/Problem Drinking Displayers. Analyses included logistic regression, univariate and multivariate Cox proportional hazard analysis and multi-state Markov modeling. A total of 338 participants were recruited, 56.1% were female, 74.8% were Caucasian, and 58.8% were from University A. At baseline, 68 Facebook profiles (20.1%) included displayed alcohol references. During the first year of college, 135 (39.9%) profiles newly displayed alcohol. In multivariate Cox proportional hazard analysis, university (University B versus A, HR = 0.47, 95% CI: 0.28–0.77, p = 0.003), number of Facebook friends (HR = 1.19, 95% CI: 1.09–1.28, p < 0.001 for every 100 more friends), and average monthly status updates (HR = 1.03, 95% CI: 1.002–1.05, p = 0.033) were identified as independent predictors for new alcohol display. Findings contribute to understanding the patterns and predictors for displayed alcohol references on Facebook. PMID:24415846

Expression of miR-146a-5p in patients with intracranial aneurysms and its association with prognosis.

PubMed

Zhang, H-L; Li, L; Cheng, C-J; Sun, X-C

2018-02-01

The study aims to detect the association of miR-146a-5p with intracranial aneurysms (IAs). The expression of miR-146a-5p was compared from plasma samples between 72 patients with intracranial aneurysms (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed to analyze the relationship between miR-146a-5p expression and clinical data and overall survival (OS) time of IAs patients. Univariate and multivariate Cox proportional hazards have also been performed. Notably, higher miR-146a-5p expression was found in plasma samples from 72 patients with intracranial aneurysms (IAs) compared with 40 healthy controls. Higher miR-146a-5p expression was significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan-Meier survival analysis verified that higher miR-146a-5p expression predicted a shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs patients. Univariate and multivariate Cox proportional hazards demonstrated that higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk factors of OS in patients with intracranial aneurysms (IAs). MiR-146a-5p expression may serve as a biomarker for predicting prognosis in patients with IAs.

MiR-221, a potential prognostic biomarker for recurrence in papillary thyroid cancer.

PubMed

Dai, Lei; Wang, Yaozong; Chen, Liangliang; Zheng, Jueru; Li, Jianjun; Wu, Xianjiang

2017-01-07

Many studies have reported several transcriptionally deregulated microRNAs (miRNAs) in papillary thyroid cancer (PTC) tissue in comparison with benign thyroid nodules and normal thyroid tissues. However, the correlation between miRNA expressions and PTC recurrence still remains unclear. The PTC patients who scheduled to undergo total thyroidectomy by the same surgical team in Ningbo NO.2 Hospital from March 1998 to March 2008 were enrolled in this study. The clinical and pathological characteristics of each patient were recorded in detail. The selected miRNA expressions were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Potential predictive factors for cancer recurrence were evaluated by univariate and multivariate Cox proportional hazard analysis. A total of 78 patients were enrolled with 49 females at a mean age of 45.8 years. Enrolled patients were divided into two groups: nonrecurrent group (n = 54) and recurrent group (n = 24). The results from the univariate Cox proportional hazard analysis revealed that primary tumor size, TNM stage, extrathyroid extension, miR-221, and miR-222 expressions were significantly associated with PTC recurrence (P < 0.05). The tissue expression of miR-221 was the only independent risk factor for PTC recurrence (HR 1.41; 95%CI 1.14-1.95, P = 0.007) by multiple Cox proportional hazard analysis. This study identified the potential role of miR-221 as a prognostic biomarker for the recurrence in PTC.

Effects of cicletanine in the left circumflex coronary artery occlusion-reperfusion canine model of sudden death: analysis of 107 experiments using Cox's proportional hazards model.

PubMed

Jouve, R; Puddu, P E; Langlet, F; Lanti, M; Guillen, J C; Rolland, P H; Serradimigni, A

1988-01-01

Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine. Since cicletanine-treated dogs had reduced mean ST segment elevation at 3 min post-occlusion, lower incidence of early post-occlusion (0-10 min) sustained ventricular tachycardia, and increased endogenous production of prostacyclin, and the latter was inversely correlated with the level of ST segment elevation, it is concluded that such favourable effects on the ischaemic myocardium were contributory to the improved outcome in these experiments. These effects on the ischaemic myocardium obtained in spite of a hypotensive action in the experimental setting might be regarded as desirable and it is therefore suggested that they should be further investigated by pharmacodynamic studies in human subjects.

Co-expression of COX-2 and 5-LO in primary glioblastoma is associated with poor prognosis.

PubMed

Wang, Xingfu; Chen, Yupeng; Zhang, Sheng; Zhang, Lifeng; Liu, Xueyong; Zhang, Li; Li, Xiaoling; Chen, Dayang

2015-11-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) are important factors in tumorigenesis and malignant progression; however, studies of their roles in glioblastoma have produced conflicting results. To define the frequencies of COX-2 and 5-LO expression and their correlation with clinicopathological features and prognosis, tumor tissues from 76 cases of newly diagnosed primary ordinary glioblastoma were examined for COX-2 and 5-LO expression by immunohistochemistry. The expression levels of COX-2 and 5-LO and the relationships between the co-expression of COX-2/5-LO and patient age and gender, edema index (EI), Karnofsky Performance Scale and overall survival (OS) were analyzed. COX-2 and 5-LO were expressed in 73.7 % (56/76) and 92.1 % (70/76) of the samples, respectively. Among the clinicopathological characteristics, only age (>60 years) exhibited a significant association with the high expression of COX-2. No statistically significant correlations were found in the 5-LO cohort. A significant positive correlation was revealed between the COX-2 and 5-LO scores (r = 0.374; p = 0.001). The elevated co-expression of COX-2 and 5-LO was observed primarily in the patients over the age of 60 years. Patients with a high expression of COX-2 had a significantly shorter OS (p < 0.01), whereas the immunoexpression of 5-LO was not associated with the OS of patients with glioblastoma. Survival analysis indicated that simultaneous high levels of COX-2 and 5-LO expression were significantly correlated with poor OS and, conversely, that a low/low expression pattern of these two proteins was significantly associated with better OS (p < 0.05). Moreover, the Cox multivariable proportional hazard model showed that a high expression of COX-2, high co-expression of COX-2 and 5-LO, and a high Ki-67 index were significant predictors of shorter OS in primary glioblastoma, independent of age, gender, EI, 5-LO expression and p53 status. The hazard ratios for OS were 2.347 (95 % CI 1.30-4.25, p = 0.005), 1.900 (95 % CI 1.30-2.78, p = 0.001), and 2.210 (95 % CI 1.19-4.09, p = 0.011), respectively. These results suggest that COX-2 and 5-LO play roles in tumorigenesis and the progression of primary glioblastoma and that the co-expression pattern of COX-2/5-LO may be used as an independent prognostic factor in this disease.

Prognostic factors and relative risk for survival in N1-3 oral squamous cell carcinoma: a multivariate analysis using Cox's hazard model.

PubMed

Noguchi, M; Kido, Y; Kubota, H; Kinjo, H; Kohama, G

1999-12-01

The records of 136 patients with N1-3 oral squamous cell carcinoma treated by surgery were investigated retrospectively, with the aim of finding out which factors were predictive of survival on multivariate analysis. Four independent factors significantly influenced survival in the following order: pN stage; T stage; histological grade; and N stage. The most significant was pN stage, the five-year survival for patients with pN0 being 91% and for patients with pN1-3 41%. A further study was carried out on the 80 patients with pN1-3 to find out their prognostic factors for survival and the independent factors identified by multivariate analysis were T stage and presence or absence of extracapsular spread to metastatic lymph nodes.

Knowledge of HIV seropositivity is a predictor for initiation of illicit drug use: incidence of drug use initiation among female sex workers in a high HIV-prevalence area of China

PubMed Central

Wang, Haibo; Brown, Katherine S.; Wang, Guixiang; Ding, Guowei; Zang, Chunpeng; Wang, Junjie; Reilly, Kathleen H.; Chen, Helen; Wang, Ning

2012-01-01

Background Drug use and sex work have had facilitative roles in the transmission of HIV/AIDS in China. Stopping drug use among sex workers may help to control the growth of the HIV/AIDS epidemic among Chinese sex workers. Methods From March 2006 to November 2009, female sex workers (FSW) in Kaiyuan City, Yunnan, China were recruited into an open cohort study. Participants were interviewed and tested for drug use and HIV/sexually transmitted infection (STI) prevalence. Follow-up surveys were conducted every six months. Multivariate Cox proportional hazards regression model with time dependent variables was used to measure the associations between independent variables and drug initiation. Results During the course of the study, 66 (8.8%) FSWs initiated drug use yielding an overall incidence of 6.0 per 100 person years (PY) (95% confidence interval [CI], 4.67–7.58). In the multivariate Cox proportional hazards regression model, being HIV-positive and aware of positive serostatus (adjusted hazard ratio [AHR] 2.6, 95% CI 1.24–5.55), age at initiation of commercial sex work <20 years (AHR 1.8, 95% CI 1.12–3.01), and working in a high-risk establishment (AHR 1.9, 95% CI 1.14–3.04) were associated with illicit drug initiation. Conclusions Being HIV-positive and aware of positive serostatus was the most salient predictor for the initiation of illicit drug use. Interventions offering sources of education, treatment, support, and counseling to HIV-positive FSWs need to be implemented in order to help promote self-efficacy and safe behaviors among this group of high-risk women. PMID:21402453

[Relationship between inflammatory markers and the risk of colorectal cancer in Kailuan male cohort].

PubMed

Wang, G; Xu, W G; Li, F; Su, K; Li, N; Lü, Z Y; Feng, X S; Wei, L P; Chen, H D; Chen, Y H; Guo, L W; Cui, H; Yang, W J; Li, Z F; Ren, J S; Wu, S L; Shi, J F; Dai, M; He, J

2017-10-31

Objective: To investigate whether elevated levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) at baseline are associated with an increased risk of colorectal cancer in Kailuan male cohort. Methods: Since May 2006, males from Kailuan cohort were included in this study. Information on demographics, medical history, anthropometry, hsCRP and NE were collectedat baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios ( HR ) of association between baseline hsCRP and NE and colorectal cancer risk. Results: By December 31, 2015, a total of 73 869 participants were enrolled in this study. During the follow-up, 336 incident colorectal cancer cases were identified. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of colorectal cancer were 456/10(5,) 510/10(5) and 746/10(5) in these 3 groups, respectively (χ(2)=10.79, P =0.005). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significant increased risks of colorectal cancer ( HR =1.38, 95% CI: 1.05-1.81, P =0.020)after adjusting for age, gender, smoking, drinking, BMI, diabetes and income. Furthermore, subjects were divided into two groups according to the level of NE (≤ 4.08×10(9)/L and > 4.08×10(9)/L). Multivariable Cox proportional hazards regression models indicated that there is no statistical significance of association between NE and colorectal cancer. Conclusions: Elevated levels of hsCRP at baseline might increase the risk of colorectal cancer in males.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

PubMed

Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2018-06-19

To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

Hypertension Control in Adults With Diabetes Mellitus and Recurrent Cardiovascular Events: Global Results From the Trial Evaluating Cardiovascular Outcomes With Sitagliptin.

PubMed

Navar, Ann Marie; Gallup, Dianne S; Lokhnygina, Yuliya; Green, Jennifer B; McGuire, Darren K; Armstrong, Paul W; Buse, John B; Engel, Samuel S; Lachin, John M; Standl, Eberhard; Van de Werf, Frans; Holman, Rury R; Peterson, Eric D

2017-11-01

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function. © 2017 American Heart Association, Inc.

The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

PubMed

Bišof, V; Salihović, M Peričić; Narančić, N Smolej; Skarić-Jurić, T; Jakić-Razumović, J; Janićijević, B; Rudan, P

2012-06-01

The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

Are There Differences in Treatment and Survival Between Poor, Older Black and White Women with Breast Cancer?

PubMed

Aggarwal, Himani; Callahan, Christopher M; Miller, Kathy D; Tu, Wanzhu; Loehrer, Patrick J

2015-10-01

To explore differences in treatment and survival outcome between poor, older black and white women with breast cancer. Retrospective cohort study. Public safety net hospital. Women aged 65 and older diagnosed with breast cancer from 1999 to 2008 (n = 1,000). Breast cancer treatments that black and white women sought were compared using the Pearson chi-square test. All-cause mortality of black and white women was compared using hazard ratios derived from a multivariate Cox proportional hazards model. There was no significant difference between older black and white women in surgical treatment, radiation therapy, chemotherapy, or hormone therapy over the study period. Race was not a significant predictor of survival in the Cox proportional hazards model that controlled for stage of cancer, age at diagnosis, dual-eligibility status, comorbid conditions, body mass index, smoking history, mammogram screening, and treatment for breast cancer. Race did not appear to affect treatment or mortality in a cohort of older women with low socioeconomic status. This may be associated with similar healthcare delivery and equivalent access to health care for the older black and white women in this study. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Acupuncture Therapy and Incidence of Depression After Stroke.

PubMed

Lu, Chung-Yen; Huang, Hsin-Chia; Chang, Hen-Hong; Yang, Tsung-Hsien; Chang, Chee-Jen; Chang, Su-Wei; Chen, Pei-Chun

2017-06-01

We investigated whether use of acupuncture within a 3-month poststroke period after hospital discharge is associated with reduced risk of depression. This cohort study included 16 046 patients aged ≥18 years with an initial hospitalization for stroke during 2000 and 2012 in the claims database of a universal health insurance program. Patients who had received acupuncture therapies within 3 months of discharge were defined as acupuncture users (n=1714). All patients were followed up for incidence of depression until the end of 2013. We assessed the association between use of acupuncture and incidence of depression using Cox proportional hazards models in all subjects and in propensity score-matched samples consisting of 1714 pairs of users and nonusers. During the follow-up period, the incidence of depression per 1000 person-years was 11.1 and 9.7 in users and nonusers, respectively. Neither multivariable-adjusted Cox models (hazard ratio, 1.04; 95% confidence interval, 0.84-1.29) nor the propensity score-matching model (hazard ratio, 1.06; 95% confidence interval, 0.79-1.42) revealed an association between use of acupuncture and incidence of depression. In patients admitted to hospital for stroke, acupuncture therapy within 3 months after discharge was not associated with subsequent incidence of depression. © 2017 American Heart Association, Inc.

Charlson comorbidity index as a predictor of periodontal disease in elderly participants

PubMed Central

2018-01-01

Purpose This study investigated the validity of the Charlson comorbidity index (CCI) as a predictor of periodontal disease (PD) over a 12-year period. Methods Nationwide representative samples of 149,785 adults aged ≥60 years with PD (International Classification of Disease, 10th revision [ICD-10], K052–K056) were derived from the National Health Insurance Service-Elderly Cohort during 2002–2013. The degree of comorbidity was measured using the CCI (grade 0–6), including 17 diseases weighted on the basis of their association with mortality, and data were analyzed using multivariate Cox proportional-hazards regression in order to investigate the associations of comorbid diseases (CDs) with PD. Results The multivariate Cox regression analysis with adjustment for sociodemographic factors (sex, age, household income, insurance status, residence area, and health status) and CDs (acute myocardial infarction, congestive heart failure, peripheral vascular disease, cerebral vascular accident, dementia, pulmonary disease, connective tissue disorders, peptic ulcer, liver disease, diabetes, diabetes complications, paraplegia, renal disease, cancer, metastatic cancer, severe liver disease, and human immunodeficiency virus [HIV]) showed that the CCI in elderly comorbid participants was significantly and positively correlated with the presence of PD (grade 1: hazard ratio [HR], 1.11; P<0.001; grade ≥2: HR, 1.12, P<0.001). Conclusions We demonstrated that a higher CCI was a significant predictor of greater risk for PD in the South Korean elderly population. PMID:29770238

Confidence intervals for the first crossing point of two hazard functions.

PubMed

Cheng, Ming-Yen; Qiu, Peihua; Tan, Xianming; Tu, Dongsheng

2009-12-01

The phenomenon of crossing hazard rates is common in clinical trials with time to event endpoints. Many methods have been proposed for testing equality of hazard functions against a crossing hazards alternative. However, there has been relatively few approaches available in the literature for point or interval estimation of the crossing time point. The problem of constructing confidence intervals for the first crossing time point of two hazard functions is considered in this paper. After reviewing a recent procedure based on Cox proportional hazard modeling with Box-Cox transformation of the time to event, a nonparametric procedure using the kernel smoothing estimate of the hazard ratio is proposed. The proposed procedure and the one based on Cox proportional hazard modeling with Box-Cox transformation of the time to event are both evaluated by Monte-Carlo simulations and applied to two clinical trial datasets.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

[Risk factors on the recurrence of ischemic stroke and the establishment of a Cox's regression model].

PubMed

An, Ya-chen; Chen, Yun-xia; Wang, Yu-xun; Zhao, Xiao-jing; Wang, Yan; Zhang, Jiang; Li, Chun-ling; Peng, Yan-bo; Gao, Su-ling; Chang, Li-sha; Zhang, Li; Xue, Xin-hong; Chen, Rui-ying; Wang, Da-li

2011-08-01

To investigate the risk factors and establish the Cox's regression model on the recurrence of ischemic stroke. We retrospectively reviewed consecutive patients with ischemic stroke admitted to the Neurology Department of the Hebei United University Affiliated Hospital between January 1, 2008 and December 31, 2009. Cases had been followed since the onset of ischemic stroke. The follow-up program was finished in June 30, 2010. Kaplan-Meier methods were used to describe the recurrence rate. Monovariant and multivariate Cox's proportional hazard regression model were used to analyze the risk factors associated to the episodes of recurrence. And then, a recurrence model was set up. During the period of follow-up program, 79 cases were relapsed, with the recurrence rates as 12.75% in one year and 18.87% in two years. Monovariant and multivariate Cox's proportional hazard regression model showed that the independent risk factors that were associated with the recurrence appeared to be age (X₁) (RR = 1.025, 95%CI: 1.003 - 1.048), history of hypertension (X₂) (RR = 1.976, 95%CI: 1.014 - 3.851), history of family strokes (X₃) (RR = 2.647, 95%CI: 1.175 - 5.961), total cholesterol amount (X₄) (RR = 1.485, 95%CI: 1.214 - 1.817), ESRS total scores (X₅) (RR = 1.327, 95%CI: 1.057 - 1.666) and progression of the disease (X₆) (RR = 1.889, 95%CI: 1.123 - 3.178). Personal prognosis index (PI) of the recurrence model was as follows: PI = 0.025X₁ + 0.681X₂ + 0.973X₃ + 0.395X₄ + 0.283X₅ + 0.636X₆. The smaller the personal prognosis index was, the lower the recurrence risk appeared, while the bigger the personal prognosis index was, the higher the recurrence risk appeared. Age, history of hypertension, total cholesterol amount, total scores of ESRS, together with the disease progression were the independent risk factors associated with the recurrence episodes of ischemic stroke. Both recurrence model and the personal prognosis index equation were successful constructed.

Application and validation of Cox regression models in a single-center series of double kidney transplantation.

PubMed

Santori, G; Fontana, I; Bertocchi, M; Gasloli, G; Magoni Rossi, A; Tagliamacco, A; Barocci, S; Nocera, A; Valente, U

2010-05-01

A useful approach to reduce the number of discarded marginal kidneys and to increase the nephron mass is double kidney transplantation (DKT). In this study, we retrospectively evaluated the potential predictors for patient and graft survival in a single-center series of 59 DKT procedures performed between April 21, 1999, and September 21, 2008. The kidney recipients of mean age 63.27 +/- 5.17 years included 16 women (27%) and 43 men (73%). The donors of mean age 69.54 +/- 7.48 years included 32 women (54%) and 27 men (46%). The mean posttransplant dialysis time was 2.37 +/- 3.61 days. The mean hospitalization was 20.12 +/- 13.65 days. Average serum creatinine (SCr) at discharge was 1.5 +/- 0.59 mg/dL. In view of the limited numbers of recipient deaths (n = 4) and graft losses (n = 8) that occurred in our series, the proportional hazards assumption for each Cox regression model with P < .05 was tested by using correlation coefficients between transformed survival times and scaled Schoenfeld residuals, and checked with smoothed plots of Schoenfeld residuals. For patient survival, the variables that reached statistical significance were donor SCr (P = .007), donor creatinine cleararance (P = .023), and recipient age (P = .047). Each significant model passed the Schoenfeld test. By entering these variables into a multivariate Cox model for patient survival, no further significance was observed. In the univariate Cox models performed for graft survival, statistical significance was noted for donor SCr (P = .027), SCr 3 months post-DKT (P = .043), and SCr 6 months post-DKT (P = .017). All significant univariate models for graft survival passed the Schoenfeld test. A final multivariate model retained SCr at 6 months (beta = 1.746, P = .042) and donor SCr (beta = .767, P = .090). In our analysis, SCr at 6 months seemed to emerge from both univariate and multivariate Cox models as a potential predictor of graft survival among DKT. Multicenter studies with larger recipient populations and more graft losses should be performed to confirm our findings. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Quantitative Analysis of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Yi; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo; Song, Jie

Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). Conclusion: Quantitative analysis identified novel {sup 18}F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.« less

Coexpression of aPKCλ/ι and IL-6 in prostate cancer tissue correlates with biochemical recurrence.

PubMed

Ishiguro, Hitoshi; Akimoto, Kazunori; Nagashima, Yoji; Kagawa, Eriko; Sasaki, Takeshi; Sano, Jin-yu; Takagawa, Ryo; Fujinami, Kiyoshi; Sasaki, Kazunori; Aoki, Ichiro; Ohno, Shigeo; Kubota, Yoshinobu; Uemura, Hiroji

2011-08-01

Atypical protein kinase C λ/ι (aPKCλ/ι) and interleukin-6 (IL-6) have been implicated in prostate cancer progression, the mechanisms of which have been demonstrated both in vitro and in vivo. However, the clinical significance of the correlation between the expressions of these factors remains to be clarified. In the present study, we report a significant correlation between aPKCλ/ι and IL-6 proteins in prostate cancer tissue by immunohistochemical staining. We evaluated the association of both proteins by analyzing clinicopathological parameters using chi-square test, Kaplan-Meier with log-rank test, and a Cox proportional hazard regression model in univariate and multivariate analyses. The results again showed that the expression of aPKCλ/ι and IL-6 correlates in prostate cancer tissue (P < 0.001). Atypical protein kinase C λ/ι was also found to correlate with the Gleason score (P < 0.001) and with biochemical recurrence after prostatectomy (P = 0.02). Furthermore, aPKCλ/ι correlated with biochemical recurrence in a Kaplan-Meier and log-rank test (P = 0.01) and Cox analysis (P = 0.02 in the univariate analysis, P = 0.02 in the multivariate analysis). The coexpression of aPKCλ/ι and IL-6 also correlated with biochemical recurrence by Kaplan-Meier and log-rank test (P = 0.005) and Cox analysis (P = 0.01 in the univariate analysis, P = 0.03 in the multivariate analysis). These results indicate a strong correlation between aPKCλ/ι and IL-6 in prostate tumors, and that the aPKCλ/ι-IL-6 axis is a reliable prognostic factor for the biochemical recurrence of this cancer. © 2011 Japanese Cancer Association.

SYNTAX score based on coronary computed tomography angiography may have a prognostic value in patients with complex coronary artery disease: An observational study from a retrospective cohort.

PubMed

Suh, Young Joo; Han, Kyunghwa; Chang, Suyon; Kim, Jin Young; Im, Dong Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Hur, Jin; Kim, Young Jin; Choi, Byoung Wook

2017-09-01

The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score is an invasive coronary angiography (ICA)-based score for quantifying the complexity of coronary artery disease (CAD). Although the SYNTAX score was originally developed based on ICA, recent publications have reported that coronary computed tomography angiography (CCTA) is a feasible modality for the estimation of the SYNTAX score.The aim of our study was to investigate the prognostic value of the SYNTAX score, based on CCTA for the prediction of major adverse cardiac and cerebrovascular events (MACCEs) in patients with complex CAD.The current study was approved by the institutional review board of our institution, and informed consent was waived for this retrospective cohort study. We included 251 patients (173 men, mean age 66.0 ± 9.29 years) who had complex CAD [3-vessel disease or left main (LM) disease] on CCTA. SYNTAX score was obtained on the basis of CCTA. Follow-up clinical outcome data regarding composite MACCEs were also obtained. Cox proportional hazards models were developed to predict the risk of MACCEs based on clinical variables, treatment, and computed tomography (CT)-SYNTAX scores.During the median follow-up period of 1517 days, there were 48 MACCEs. Univariate Cox hazards models demonstrated that MACCEs were associated with advanced age, low body mass index (BMI), and dyslipidemia (P < .2). In patients with LM disease, MACCEs were associated with a higher SYNTAX score. In patients with CT-SYNTAX score ≥23, patients who underwent coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention had significantly lower hazard ratios than patients who were treated with medication alone. In multivariate Cox hazards model, advanced age, low BMI, and higher SYNTAX score showed an increased hazard ratio for MACCE, while treatment with CABG showed a lower hazard ratio (P < .2).On the basis of our results, CT-SYNTAX score can be a useful method for noninvasively predicting MACCEs in patients with complex CAD, especially in patients with LM disease.

African American Race is an Independent Risk Factor in Survival from Initially Diagnosed Localized Breast Cancer

PubMed Central

Wieder, Robert; Shafiq, Basit; Adam, Nabil

2016-01-01

BACKGROUND: African American race negatively impacts survival from localized breast cancer but co-variable factors confound the impact. METHODS: Data sets were analyzed from the Surveillance, Epidemiology and End Results (SEER) directories from 1973 to 2011 consisting of patients with designated diagnosis of breast adenocarcinoma, race as White or Caucasian, Black or African American, Asian, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, age, stage I, II or III, grade 1, 2 or 3, estrogen receptor or progesterone receptor positive or negative, marital status as single, married, separated, divorced or widowed and laterality as right or left. The Cox Proportional Hazards Regression model was used to determine hazard ratios for survival. Chi square test was applied to determine the interdependence of variables found significant in the multivariable Cox Proportional Hazards Regression analysis. Cells with stratified data of patients with identical characteristics except African American or Caucasian race were compared. RESULTS: Age, stage, grade, ER and PR status and marital status significantly co-varied with race and with each other. Stratifications by single co-variables demonstrated worse hazard ratios for survival for African Americans. Stratification by three and four co-variables demonstrated worse hazard ratios for survival for African Americans in most subgroupings with sufficient numbers of values. Differences in some subgroupings containing poor prognostic co-variables did not reach significance, suggesting that race effects may be partly overcome by additional poor prognostic indicators. CONCLUSIONS: African American race is a poor prognostic indicator for survival from breast cancer independent of 6 associated co-variables with prognostic significance. PMID:27698895

Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p < 0.001) and severe PH (HR 2.068, 95% CI: 1.715 to 2.493, p < 0.001). Further assessment by multivariate Cox models identified significant risk for death for mild PH (HR 1.433, 95% CI: 1.203 to 1.706, p < 0.001) and severe PH (HR 1.597, 95% CI: 1.308 to 1.949, p < 0.001). Propensity score matching confirmed the risk for death for mild PH (HR 1.530, 95% CI: 1.189 to 1.969, p = 0.001) and severe PH (HR 2.103, 95% CI: 1.436 to 3.078, p < 0.001). The manifestation of PH, even with mild severity, is associated with significantly increased risk for death among patients with idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Semi-parametric regression model for survival data: graphical visualization with R

PubMed Central

2016-01-01

Cox proportional hazards model is a semi-parametric model that leaves its baseline hazard function unspecified. The rationale to use Cox proportional hazards model is that (I) the underlying form of hazard function is stringent and unrealistic, and (II) researchers are only interested in estimation of how the hazard changes with covariate (relative hazard). Cox regression model can be easily fit with coxph() function in survival package. Stratified Cox model may be used for covariate that violates the proportional hazards assumption. The relative importance of covariates in population can be examined with the rankhazard package in R. Hazard ratio curves for continuous covariates can be visualized using smoothHR package. This curve helps to better understand the effects that each continuous covariate has on the outcome. Population attributable fraction is a classic quantity in epidemiology to evaluate the impact of risk factor on the occurrence of event in the population. In survival analysis, the adjusted/unadjusted attributable fraction can be plotted against survival time to obtain attributable fraction function. PMID:28090517

Impact of scalp location on survival in head and neck melanoma: A retrospective cohort study.

PubMed

Xie, Charles; Pan, Yan; McLean, Catriona; Mar, Victoria; Wolfe, Rory; Kelly, John

2017-03-01

Scalp melanomas have more aggressive clinicopathological features than other melanomas and mortality rates more than twice that of melanoma located elsewhere. We sought to describe the survival of patients with scalp melanoma versus other cutaneous head and neck melanoma (CHNM), and explore a possible independent negative impact of scalp location on CHNM survival. A retrospective cohort study was performed of all invasive primary CHNM cases seen at a tertiary referral center over a 20-year period. Melanoma-specific survival (MSS) was compared between scalp melanoma and other invasive CHNM. Multivariable Cox proportional hazards regression was performed to determine associations with survival. On univariate analysis, patients with scalp melanoma had worse MSS than other CHNM (hazard ratio 2.22, 95% confidence interval 1.59-3.11). Scalp location was not associated with MSS in CHNM on multivariable analysis (hazard ratio 1.11, 95% confidence interval 0.77-1.61) for all tumors together, but remained independently associated with MSS for the 0.76- to 1.50-mm thickness stratum (hazard ratio 5.51, 95% confidence interval 1.55-19.59). Disease recurrence was not assessed because of unavailable data. The poorer survival of scalp melanoma is largely explained by greater Breslow thickness and a higher proportion of male patients. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Simulation program for estimating statistical power of Cox's proportional hazards model assuming no specific distribution for the survival time.

PubMed

Akazawa, K; Nakamura, T; Moriguchi, S; Shimada, M; Nose, Y

1991-07-01

Small sample properties of the maximum partial likelihood estimates for Cox's proportional hazards model depend on the sample size, the true values of regression coefficients, covariate structure, censoring pattern and possibly baseline hazard functions. Therefore, it would be difficult to construct a formula or table to calculate the exact power of a statistical test for the treatment effect in any specific clinical trial. The simulation program, written in SAS/IML, described in this paper uses Monte-Carlo methods to provide estimates of the exact power for Cox's proportional hazards model. For illustrative purposes, the program was applied to real data obtained from a clinical trial performed in Japan. Since the program does not assume any specific function for the baseline hazard, it is, in principle, applicable to any censored survival data as long as they follow Cox's proportional hazards model.

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

PubMed

Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Machiavelli, M; Leone, B; Romero, A; Rodriguez, R; Cuevas, M; Dansky, C

1992-01-01

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

A multivariate analysis of prognostic factors for melanoma patients with lesions greater than or equal to 3.65 mm in thickness. The importance of revealing alternative Cox models.

PubMed Central

Day, C L; Lew, R A; Mihm, M C; Sober, A J; Harris, M N; Kopf, A W; Fitzpatrick, T B; Harrist, T J; Golomb, F M; Postel, A; Hennessey, P; Gumport, S L; Raker, J W; Malt, R A; Cosimi, A B; Wood, W C; Roses, D F; Gorstein, F; Rigel, D; Friedman, R J; Mintzis, M M; Grier, R W

1982-01-01

Fourteen prognostic factors were examined in 79 patients with clinical Stage I melanoma greater than or equal to 3.65 mm in thickness. All nine patients with melanoma of the hands or feet died of melanoma. A Cox proportional hazards (multivariate) analysis of the remaining 70 patients showed that a combination of the following four variables best predicted bony or visceral metastases: 1) a nearly absent or minimal lymphocyte response at the base of the tumor, 2) histologic type other than superficial spreading melanoma, 3) location on the trunk, and 4) positive nodes or no initial node dissection. Ulceration and/or ulceration width were not useful in predicting outcome either singly or in combination with other variables. Patients with negative lymph nodes and primary tumors of the trunk, hands, and feet did not do better than patients with positive nodes at those sites. Conversely, non of 16 patients with negative lymph nodes and extremity melanomas (excluding the hands and feet) or head and neck melanomas developed visceral or bony metastases (i.e., five-year disease-free survival rate 100%). PMID:7055383

Misspecification of Cox regression models with composite endpoints

PubMed Central

Wu, Longyang; Cook, Richard J

2012-01-01

Researchers routinely adopt composite endpoints in multicenter randomized trials designed to evaluate the effect of experimental interventions in cardiovascular disease, diabetes, and cancer. Despite their widespread use, relatively little attention has been paid to the statistical properties of estimators of treatment effect based on composite endpoints. We consider this here in the context of multivariate models for time to event data in which copula functions link marginal distributions with a proportional hazards structure. We then examine the asymptotic and empirical properties of the estimator of treatment effect arising from a Cox regression model for the time to the first event. We point out that even when the treatment effect is the same for the component events, the limiting value of the estimator based on the composite endpoint is usually inconsistent for this common value. We find that in this context the limiting value is determined by the degree of association between the events, the stochastic ordering of events, and the censoring distribution. Within the framework adopted, marginal methods for the analysis of multivariate failure time data yield consistent estimators of treatment effect and are therefore preferred. We illustrate the methods by application to a recent asthma study. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22736519

A FORTRAN program for multivariate survival analysis on the personal computer.

PubMed

Mulder, P G

1988-01-01

In this paper a FORTRAN program is presented for multivariate survival or life table regression analysis in a competing risks' situation. The relevant failure rate (for example, a particular disease or mortality rate) is modelled as a log-linear function of a vector of (possibly time-dependent) explanatory variables. The explanatory variables may also include the variable time itself, which is useful for parameterizing piecewise exponential time-to-failure distributions in a Gompertz-like or Weibull-like way as a more efficient alternative to Cox's proportional hazards model. Maximum likelihood estimates of the coefficients of the log-linear relationship are obtained from the iterative Newton-Raphson method. The program runs on a personal computer under DOS; running time is quite acceptable, even for large samples.

Intake of Fiber and Nuts during Adolescence and Incidence of Proliferative Benign Breast Disease

PubMed Central

Su, Xuefen; Tamimi, Rulla M.; Collins, Laura C.; Baer, Heather J.; Cho, Eunyoung; Sampson, Laura; Willett, Walter C.; Schnitt, Stuart J.; Connolly, James L.; Rosner, Bernard A.; Colditz, Graham A.

2011-01-01

Objective We examined the association between adolescent fiber intake and proliferative BBD, a marker of increased breast cancer risk, in the Nurses’ Health Study II. Methods Among 29,480 women who completed a high school diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Multivariate-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD (multivariate HR (95% CI): 0.75 (0.59, 0.96), p-trend = 0.01) than women in the lowest quintile. High school intake of nuts and apples was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk (multivariate HR (95% CI): 0.64 (0.48, 0.85), p-trend < 0.01) than women consuming <1 serving/month. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the high school diet questionnaire. Conclusions These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influence subsequent risk of breast disease and may suggest a viable means for breast cancer prevention. PMID:20229245

Comparing initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care: A study of Irish National data.

PubMed

Doherty, Sarah M; Jackman, Louise M; Kirwan, John F; Dunne, Deirdre; O'Connor, Kieran G; Rouse, John M

2016-12-01

The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure　- Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

PubMed

Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

2016-05-25

It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse Probability of Treatment Weighted Analysis.

PubMed

Chaiteerakij, Roongruedee; Chattieng, Piyanat; Choi, Jonggi; Pinchareon, Nutcha; Thanapirom, Kessirin; Geratikornsupuk, Nopavut

Evidence supporting benefit of hepatocellular carcinoma (HCC) surveillance in reducing mortality is not well-established. The effect of HCC surveillance in reducing mortality was assessed by an inverse probability of treatment weighting (IPTW)-based analysis controlled for inherent bias and confounders in observational studies. This retrospective cohort study was conducted on 446 patients diagnosed with HCC between 2007 and 2013 at a major referral center. Surveillance was defined as having at least 1 ultrasound test within a year before HCC diagnosis. Primary outcome was survival estimated using the Kaplan-Meier method with lead-time bias adjustment and compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were computed using conventional Cox and weighted Cox proportional hazards analysis with IPTW adjustment. Of the 446 patients, 103 (23.1%) were diagnosed with HCC through surveillance. The surveillance group had more patients with the Barcelona-Clinic Liver Cancer stage A (80.6% vs. 33.8%, P < 0.0001), more patients eligible for potentially curative treatment (73.8% vs. 44.9%, P < 0.0001), and longer median survival (49.6 vs. 15.9 months, P < 0.0001). By conventional multivariate Cox analysis, HR (95% CI) of surveillance was 0.63 (0.45-0.87), P = 0.005. The estimated effect of surveillance remained similar in the IPTW-adjusted Cox analysis (HR: 0.57; 95% CI: 0.43-0.76, P < 0.001). HCC surveillance by ultrasound is associated with a 37% reduction in mortality. Even though surveillance is recommended in all guidelines, but in practice, it is underutilized. Interventions are needed to increase surveillance rate for improving HCC outcome.

Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children

PubMed Central

Lowenthal, Elizabeth D.; Ellenberg, Jonas H.; Machine, Edwin; Sagdeo, Aditi; Boiditswe, Sefelani; Steenhoff, Andrew P.; Rutstein, Richard; Anabwani, Gabriel; Gross, Robert

2013-01-01

Importance Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. Objective To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Design, Setting, and Participants Retrospective cohort study of children (aged 3–16 years) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. Main Outcomes and Measures The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. Results With a median follow-up time of 69 months (range, 6–112 months; interquartile range, 23–87 months), 57 children (13.5%; 95% CI, 10.4%–17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%–31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%–4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%–7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4–2.7; log rank P<.001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses. Conclusions and Relevance Among children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients. PMID:23632724

Endoscopic ultrasonography in esophageal cancer leads to improved survival rates: results from a population-based study.

PubMed

Wani, Sachin; Das, Ananya; Rastogi, Amit; Drahos, Jennifer; Ricker, Winifred; Parsons, Ruth; Bansal, Ajay; Yen, Roy; Hosford, Lindsay; Jankowski, Meghan; Sharma, Prateek; Cook, Michael B

2015-01-15

The advantages of endoscopic ultrasound (EUS) and computed tomography (CT)-positron emission tomography (PET) with respect to survival for esophageal cancer patients are unclear. This study aimed to assess the effects of EUS, CT-PET, and their combination on overall survival with respect to cases not receiving these procedures. Patients who were ≥66 years old when diagnosed with esophageal cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare linked database. Cases were split into 4 analytic groups: EUS only (n = 318), CT-PET only (n = 853), EUS+CT-PET (n = 189), and no EUS or CT-PET (n = 2439). Survival times were estimated with the Kaplan-Meier method and were compared with the log-rank test for each group versus the no EUS or CT-PET group. Multivariate Cox proportional hazards models were used to compare 1-, 3-, and 5-year survival rates. Kaplan-Meier analyses showed that EUS, CT-PET, and EUS+CT-PET patients had improved survival for all stages (with the exception of stage 0 disease) in comparison with patients undergoing no EUS or CT-PET. Receipt of EUS increased the likelihood of receiving endoscopic therapies, esophagectomy, and chemoradiation. Multivariate Cox proportional hazards models showed that receipt of EUS was a significant predictor of improved 1- (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.39-0.59; P < .0001), 3- (HR, 0.57; 95% CI, 0.48-0.66; P < .0001), and 5-year survival (HR, 0.59; 95% CI, 0.50-0.68). Similar results were noted when the results were stratified on the basis of histology and for the CT-PET and EUS+CT-PET groups. Receipt of either EUS or CT-PET alone in esophageal cancer patients was associated with improved 1-, 3-, and 5-year survival. Future studies should identify barriers to the dissemination of these staging modalities. © 2014 American Cancer Society.

Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort.

PubMed

Durán-Barragán, S; McGwin, G; Vilá, L M; Reveille, J D; Alarcón, G S

2008-07-01

To examine if angiotensin-converting enzyme (ACE) inhibitor use delays the occurrence of renal involvement and decreases the risk of disease activity in SLE patients. SLE patients (Hispanics, African Americans and Caucasians) from the lupus in minorities: nature vs nurture (LUMINA) cohort were studied. Renal involvement was defined as ACR criterion and/or biopsy-proven lupus nephritis. Time-to-renal involvement was examined by univariable and multivariable Cox proportional hazards regression analyses. Disease activity was examined with a case-crossover design and a conditional logistic regression model; in the case intervals, a decrease in the SLAM-R score >or=4 points occurred but not in the control intervals. Eighty of 378 patients (21%) were ACE inhibitor users; 298 (79%) were not. The probability of renal involvement free-survival at 10 yrs was 88.1% for users and 75.4% for non-users (P = 0.0099, log rank test). Users developed persistent proteinuria and/or biopsy-proven lupus nephritis (7.1%) less frequently than non-users (22.9%), P = 0.016. By multivariable Cox proportional hazards regression analyses, ACE inhibitors use [hazard ratio (HR) 0.27; 95% CI 0.09, 0.78] was associated with a longer time-to-renal involvement occurrence whereas African American ethnicity (HR 3.31; 95% CI 1.44, 7.61) was with a shorter time. ACE inhibitor use (54/288 case and 254/1148 control intervals) was also associated with a decreased risk of disease activity (HR 0.56; 95% CI 0.34, 0.94). ACE inhibitor use delays the development of renal involvement and associates with a decreased risk of disease activity in SLE; corroboration of these findings in other lupus cohorts is desirable before practice recommendations are formulated.

An empirical comparison of statistical tests for assessing the proportional hazards assumption of Cox's model.

PubMed

Ng'andu, N H

1997-03-30

In the analysis of survival data using the Cox proportional hazard (PH) model, it is important to verify that the explanatory variables analysed satisfy the proportional hazard assumption of the model. This paper presents results of a simulation study that compares five test statistics to check the proportional hazard assumption of Cox's model. The test statistics were evaluated under proportional hazards and the following types of departures from the proportional hazard assumption: increasing relative hazards; decreasing relative hazards; crossing hazards; diverging hazards, and non-monotonic hazards. The test statistics compared include those based on partitioning of failure time and those that do not require partitioning of failure time. The simulation results demonstrate that the time-dependent covariate test, the weighted residuals score test and the linear correlation test have equally good power for detection of non-proportionality in the varieties of non-proportional hazards studied. Using illustrative data from the literature, these test statistics performed similarly.

Putaminal dopamine depletion in de novo Parkinson's disease predicts future development of wearing-off.

PubMed

Chung, Su Jin; Lee, Yoonju; Oh, Jungsu S; Kim, Jae Seung; Lee, Phil Hyu; Sohn, Young H

2018-05-10

The present study aimed to investigate whether the level of presynaptic dopamine neuronal loss predicts future development of wearing-off in de novo Parkinson's disease. This retrospective cohort study included a total of 342 non-demented patients with de novo Parkinson's disease who underwent dopamine transporter positron emission tomography scans at their initial evaluation and received dopaminergic medications for 24 months or longer. Onset of wearing-off was determined based on patients' medical records at their outpatient clinic visits every 3-6 months. Predictive power of dopamine transporter activity in striatal subregions and other clinical factors for the development of wearing-off was evaluated by Cox proportional hazard models. During a median follow-up period of 50.2 ± 18.9 months, 69 patients (20.2%) developed wearing-off. Patients with wearing-off exhibited less dopamine transporter activity in the putamen, particularly the anterior and posterior putamens, compared to those without wearing-off. Multivariate Cox proportional hazard models revealed that dopamine transporter activities of the anterior (hazard ratio 0.556; p = 0.008) and whole putamens (hazard ratio 0.504; p = 0.025) were significant predictors of development of wearing-off. In addition, younger age at onset of Parkinson's disease, lower body weight, and a motor phenotype of postural instability/gait disturbance were also significant predictors for development of wearing-off. The present results provide in vivo evidence to support the hypothesis that presynaptic dopamine neuronal loss, particularly in the anterior putamen, leads to development of wearing-off in Parkinson's disease. Copyright © 2018. Published by Elsevier Ltd.

Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

PubMed

Giannos, Aris; Filipits, Martin; Zagouri, Flora; Brandstetter, Anita; Tsigginou, Alexandra; Sotiropoulou, Maria; Papaspyrou, Irene; Sergentanis, Theodoros N; Psaltopoulou, Theodora; Rodolakis, Alexandros; Antsaklis, Aris; Dimopoulos, Meletios-Athanasios; Dimitrakakis, Constantine

2015-01-01

In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). AR expression does not seem to play a prognostic role in TNBC.

Pressure ulcer incidence and Braden subscales: Retrospective cohort analysis in general wards of a Portuguese hospital.

PubMed

Sardo, Pedro Miguel Garcez; Guedes, Jenifer Adriana Domingues; Alvarelhão, José Joaquim Marques; Machado, Paulo Alexandre Puga; Melo, Elsa Maria Oliveira Pinheiro

2018-05-01

To study the influence of Braden subscales scores (at the first pressure ulcer risk assessment) on pressure ulcer incidence using a univariate and a multivariate time to event analysis. Retrospective cohort analysis of electronic health record database from adult patients admitted without pressure ulcer(s) to medical and surgical wards of a Portuguese hospital during 2012. The hazard ratio of developing a pressure ulcer during the length of inpatient stay was calculated by univariate Cox regression for each variable of interest and by multivariate Cox regression for the Braden subscales that were statistically significant. This study included a sample of 6552 participants. During the length of stay, 153 participants developed (at least) one pressure ulcer, giving a pressure ulcer incidence of 2.3%. The univariate time to event analysis showed that all Braden subscales, except "nutrition", were associated with the development of pressure ulcer. By multivariate analysis the scores for "mobility" and "activity" were independently predictive of the development of pressure ulcer(s) for all participants. (Im)"mobility" (the lack of ability to change and control body position) and (in)"activity" (the limited degree of physical activity) were the major risk factors assessed by Braden Scale for pressure ulcer development during the length of inpatient stay. Thus, the greatest efforts in managing pressure ulcer risk should be on "mobility" and "activity", independently of the total Braden Scale score. Copyright © 2018 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy.

PubMed

Kriege, M; Hollestelle, A; Jager, A; Huijts, P E A; Berns, E M; Sieuwerts, A M; Meijer-van Gelder, M E; Collée, J M; Devilee, P; Hooning, M J; Martens, J W M; Seynaeve, C

2014-08-26

We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.

Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol lowering drugs

PubMed Central

Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G.; Shah, Arvind K.; Lin, Jianxin

2013-01-01

In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data (IPD) in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the Deviance Information Criterion (DIC) is used to select the best transformation model. Since the model is quite complex, a novel Monte Carlo Markov chain (MCMC) sampling scheme is developed to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol lowering drugs where the goal is to jointly model the three dimensional response consisting of Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) (LDL-C, HDL-C, TG). Since the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately: however, a multivariate approach would be more appropriate since these variables are correlated with each other. A detailed analysis of these data is carried out using the proposed methodology. PMID:23580436

Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol-lowering drugs.

PubMed

Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G; Shah, Arvind K; Lin, Jianxin

2013-10-15

In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the deviance information criterion is used to select the best transformation model. Because the model is quite complex, we develop a novel Monte Carlo Markov chain sampling scheme to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol-lowering drugs where the goal is to jointly model the three-dimensional response consisting of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) (LDL-C, HDL-C, TG). Because the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately; however, a multivariate approach would be more appropriate because these variables are correlated with each other. We carry out a detailed analysis of these data by using the proposed methodology. Copyright © 2013 John Wiley & Sons, Ltd.

Surgical ablation for atrial fibrillation for two decades: are the results of new techniques equivalent to the Cox maze III procedure?

PubMed

Stulak, John M; Suri, Rakesh M; Burkhart, Harold M; Daly, Richard C; Dearani, Joseph A; Greason, Kevin L; Joyce, Lyle D; Park, Soon J; Schaff, Hartzell V

2014-05-01

A significant evolution has occurred in surgical ablation for atrial fibrillation (AF) toward alternate energy sources, lesion sets, and approaches, with the intent of simplifying the Cox maze III operation and maintaining similar outcomes. Because no large comparative studies with long-term follow-up exist, we have reviewed our experience. From January 1993 to January 2011, 1540 patients underwent surgical ablation for AF. The operations were performed in conjunction with repair of congenital heart disease in 351 (30%) and adult-acquired disease in 1189 patients (70%). In the 1189 patients, preoperative AF was paroxysmal in 598 (50%) and persistent in 591 (50%). The energy sources included cut and sew in 521 (44%), cryothermy in 267 (22%), radiofrequency in 262 (22%), and a combination in 139 patients (12%). The lesion sets included biatrial in 810 (68%), isolated pulmonary vein isolation in 269 (23%), and isolated left atrial in 110 (9%). AF ablation was performed during isolated mitral valve surgery in 516 patients (43%). The median follow-up was 33 months (maximum, 20.3 years), and late rhythm follow-up was available for 80%. The cut and sew Cox maze III procedure was superior at each follow-up interval (P = .01, P = .03, and P < .001). On multivariate analysis, the cut and sew maze procedure was independently associated with less risk of recurrent AF at a follow-up period of 1 to 5 years (hazard ratio, 0.4; 95% confidence interval, 0.24-0.69; P < .001) and >5 years (hazard ratio, 0.23; 95% confidence interval, 0.12-0.42; P < .001) for all patients. When performed during isolated mitral valve surgery, the cut and sew Cox maze III was also independently associated with less risk of recurrent AF at >5 years (hazard ratio, 0.23; 95% confidence interval, 0.08-0.66; P = .007). The cut and sew Cox maze III procedure appears to offer significantly greater freedom from AF without antiarrhythmic medications compared with alternate energy sources and lesion sets. Although alternate energy sources offer the advantage of quicker application and the possibility of minimally invasive applications, the Cox maze III operation arguably remains the reference standard for the surgical treatment of AF and should still be considered, especially for patients for whom AF ablation is of critical importance. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

The Association Between Kidney Disease and Cardiovascular Risk in a Multiethnic Cohort

PubMed Central

Nickolas, Thomas L.; Khatri, Minesh; Boden-Albala, Bernadette; Kiryluk, Krzysztof; Luo, Xiaodong; Gervasi-Franklin, Palma; Paik, Myunghee; Sacco, Ralph L.

2011-01-01

Background and Purpose The objective of this study was to determine the relationship between chronic kidney disease (CKD), race–ethnicity, and vascular outcomes. Methods A prospective, multiracial cohort of 3298 stroke-free subjects with 6.5 years of mean follow-up time for vascular outcomes (stroke, myocardial infarction, vascular death) was used. Kidney function was estimated using serum creatinine and Cockcroft-Gault formula. Cox proportional hazards models were fitted to evaluate the relationship between kidney function and vascular outcomes. Results In multivariate analysis, Cockcroft-Gault formula between 15 and 59 mL/min was associated with a significant 43% increased stroke risk in the overall cohort. Blacks with Cockcroft-Gault formula between 15 and 59 mL/min had significantly increased risk of both stroke (hazard ratio, 2.65; 95% CI, 1.47 to 4.77) and combined vascular outcomes (hazard ratio, 1.59; 95% CI, 1.10–2.92). Conclusion Chronic kidney disease is a significant risk factor for stroke and combined vascular events, especially in blacks. PMID:18617655

Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

PubMed

Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

2016-11-01

There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

New simple radiological criteria proposed for multiple primary lung cancers.

PubMed

Matsunaga, Takeshi; Suzuki, Kenji; Takamochi, Kazuya; Oh, Shiaki

2017-11-01

Controversies remain as to the differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IM) in lung cancers. We have investigated the clinical criteria for MPLC and here propose a set of new and simple criteria from the stand point of prognosis. A retrospective study was conducted on 588 consecutive patients with resected lung cancer of clinical Stage IA between 2009 and 2012. Multiple lung cancers (MLCs) were observed in 103 (17.5%) of the 588 patients. All main and other tumors were divided into solid tumor (ST) and non-solid tumor (non-ST). We defined Group A as MLCs having at least one non-ST and Group B as all tumors being ST. Cox's proportional hazard model was used for the multivariate analyses to investigate the preoperative prognostic factors. We divided the MLCs into MPLC and IM based on the preoperative prognostic factors, and survival was estimated by the Kaplan-Meier method. A multivariate analysis with Cox's proportional hazards model revealed that Group A independently predicted good overall survival (HR = 0.165, 95% CI: 0.041-0.672).Differences in the 3- and 5-year overall survivals between Groups A and B were statistically significant (96.3%/92.2% vs. 70.0%/60.0%, Pvalue = 0.0002). We suggest that Group A, defined as the presence of at least one tumor with a ground glass opacity component and clinical N0, should be excluded from the conventional concept of multiple lung cancers based on the criteria of Martini and Melamed as it has a very good prognosis. This group would be considered to be radiological MPLC. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

PubMed

Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

2017-08-01

To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

DOE Office of Scientific and Technical Information (OSTI.GOV)

Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C., E-mail: adam.berger@jefferson.edu

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluatemore » associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.« less

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study.

PubMed

Shi, Xiao; Zhang, Ting-Ting; Hu, Wei-Ping; Ji, Qing-Hai

2017-04-25

The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role.

Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study

PubMed Central

Shi, Xiao; Zhang, Ting-ting; Hu, Wei-ping; Ji, Qing-hai

2017-01-01

Background The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Results Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187–1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266–1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). Materials and Methods 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Conclusions Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role. PMID:28415710

Revisiting the role of pathological analysis in transarterial chemoembolization-treated hepatocellular carcinoma after transplantation

PubMed Central

Vasuri, Francesco; Malvi, Deborah; Rosini, Francesca; Baldin, Pamela; Fiorentino, Michelangelo; Paccapelo, Alexandro; Ercolani, Giorgio; Pinna, Antonio Daniele; Golfieri, Rita; Morselli-Labate, Antonio Maria; Grigioni, Walter Franco; D’Errico-Grigioni, Antonia

2014-01-01

AIM: To define the histopathological features predictive of post-transplant hepatocellular carcinoma (HCC) recurrence after transarterial chemoembolization, applicable for recipient risk stratification. METHODS: We retrospectively reviewed the specimens of all suspicious nodules (total 275) from 101 consecutive liver transplant recipients which came to our Pathology Unit over a 6-year period. All nodules were sampled and analyzed, and follow-up data were collected. We finally considered 11 histological variables for each patient: total number of nodules, number of viable nodules, size of the major nodule, size of the major viable nodule, occurrence of microscopic vascular invasion, maximum Edmondson's grade, clear cell/sarcomatous changes, and the residual neoplastic volume. Survival data were computed by means of the Kaplan-Meier procedure and analyzed by means of the Cox proportional hazards model. The multivariate linear regression and a k-means cluster analysis were also used in order to compute the standardized histological score. RESULTS: The total number of nodules, the residual neoplastic volume (the total volume of all evaluated nodules minus the necrotic portion) and the microvascular invasion entered the Cox multivariate hazard model with HCC recurrence as dependent variable. The histological score was therefore computed and a cluster analysis sorted recipients into 3 risk groups, with 3.3%, 18.5% and 53.8% respectively of tumor recurrence rates and 1.6%, 11.1% and 38.5% of tumor-related mortality respectively at the end of follow-up. CONCLUSION: The histological score allows a reliable stratification of HCC recurrence risk, especially in those recipients found out to be beyond the Milan criteria after orthotopic liver transplantation (OLT). PMID:25309084

Coffee consumption and risk of cardiovascular events in hypertensive patients. Results from the HARVEST.

PubMed

Palatini, Paolo; Fania, Claudio; Mos, Lucio; Garavelli, Guido; Mazzer, Adriano; Cozzio, Susanna; Saladini, Francesca; Casiglia, Edoardo

2016-06-01

Controversy still exists about the long-term cardiovascular effects of coffee consumption in hypertension. The predictive capacity of coffee use for cardiovascular events (CVEs) was investigated in 1204 participants from the HARVEST, a prospective cohort study of non-diabetic subjects aged 18-45years, screened for stage 1 hypertension. Subjects were grouped into three categories of coffee drinking, non-drinkers (none), moderate drinkers (1 to 3cups/day) and heavy drinkers (4or more cups/day). Multivariate Cox proportional hazards models were developed adjusting for possible confounding variables and risk factors. During a median follow-up of 12.6years, CVEs were developed by 60 participants. CVEs were more common among coffee drinkers than abstainers (abstainers, 2.2%; moderate drinkers, 7.0%; heavy drinkers, 14.0%; p for trend=0.0003). In a multivariable Cox regression model, coffee use was a significant predictor of CVE in both coffee categories, with a hazard ratio of 2.8 (95% CI, 1.0-7.9) in moderate coffee drinkers and of 4.5 (1.4-14.2) in heavy drinkers compared to abstainers. After inclusion of change in body weight (p=ns), incident hypertension (p=0.027) and presence of diabetes/prediabetes (p=ns) at follow-up end, the association with CVE was attenuated but remained significant in heavy coffee drinkers (HR, 95% CI, 3.4, 1.04-11.3). These data show that coffee consumption increases the risk of CVE in a linear fashion in hypertension. This association may be explained in part by the association between coffee and development of hypertension. Hypertensive patients should be discouraged from drinking coffee. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer.

PubMed

Dong, Xiaoqun; Li, Yanan; Hess, Kenneth R; Abbruzzese, James L; Li, Donghui

2011-01-01

DNA mismatch repair (MMR) maintains genomic stability and mediates cellular response to DNA damage. We aim to demonstrate whether MMR genetic variants affect overall survival (OS) in pancreatic cancer. Using the Sequenom method in genomic DNA, we retrospectively genotyped 102 single-nucleotide polymorphisms (SNPs) of 13 MMR genes from 706 patients with pancreatic adenocarcinoma seen at The University of Texas MD Anderson Cancer Center. Association between genotype and OS was evaluated using multivariable Cox proportional hazard regression models. At a false discovery rate of 1% (p ≤ .0015), 15 SNPs of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, TP73, and TREX1 in patients with localized disease (n = 333) and 6 SNPs of MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease (n = 373) were significantly associated with OS. In multivariable Cox proportional hazard regression models, SNPs of EXO1, MSH2, MSH3, PMS2L3, and TP73 in patients with localized disease, MSH2, MSH3, MSH6, and TP73 in patients with locally advanced or metastatic disease, and EXO1, MGMT, MSH2, MSH3, MSH6, PMS2L3, and TP73 in all patients remained significant predictors for OS (p ≤ .0015) after adjusting for all clinical predictors and all SNPs with p ≤ .0015 in single-locus analysis. Sixteen haplotypes of EXO1, MLH1, MSH2, MSH3, MSH6, PMS2, PMS2L3, RECQL, TP73, and TREX1 significantly correlated with OS in all patients (p ≤ .001). MMR gene variants may have potential value as prognostic markers for OS in pancreatic cancer patients.

KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma.

PubMed

Nadal, Ernest; Chen, Guoan; Prensner, John R; Shiratsuchi, Hiroe; Sam, Christine; Zhao, Lili; Kalemkerian, Gregory P; Brenner, Dean; Lin, Jules; Reddy, Rishindra M; Chang, Andrew C; Capellà, Gabriel; Cardenal, Felipe; Beer, David G; Ramnath, Nithya

2014-10-01

The aim of this study was to examine the effects of KRAS mutant subtypes on the outcome of patients with resected lung adenocarcinoma (AC). Using clinical and sequencing data, we identified 179 patients with resected lung AC for whom KRAS mutational status was determined. A multivariate Cox model was used to identify factors associated with disease-free survival (DFS) and overall survival (OS). Publicly available mutation and gene-expression data from lung cancer cell lines and lung AC were used to assess whether distinct KRAS mutant variants have a different profile. Patients with KRAS mutation had a significantly shorter DFS compared with those with KRAS wild-type (p = 0.009). Patients with KRAS-G12C mutant tumors had significantly shorter DFS compared with other KRAS mutants and KRAS wild-type tumors (p < 0.001). In the multivariate Cox model, KRAS-G12C remained as an independent prognostic marker for DFS (Hazard ratio = 2.46, 95% confidence interval 1.51-4.00, p < 0.001) and for OS (Hazard ratio = 2.35, 95% confidence interval 1.35-4.10, p = 0.003). No genes were statistically significant when comparing the mutational or transcriptional profile of lung cancer cell lines and lung AC harboring KRAS-G12C with other KRAS mutant subtypes. Gene set enrichment analysis revealed that KRAS-G12C mutants overexpressed epithelial to mesenchymal transition genes and expressed lower levels of genes predicting KRAS dependency. KRAS-G12C mutation is associated with worse DFS and OS in resected lung AC. Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRAS-G12C mutants had an epithelial to mesenchymal transition and a KRAS-independent phenotype.

Spinal cord multi-parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis.

PubMed

Querin, G; El Mendili, M M; Lenglet, T; Delphine, S; Marchand-Pauvert, V; Benali, H; Pradat, P-F

2017-08-01

Assessing survival is a critical issue in patients with amyotrophic lateral sclerosis (ALS). Neuroimaging seems to be promising in the assessment of disease severity and several studies also suggest a strong relationship between spinal cord (SC) atrophy described by magnetic resonance imaging (MRI) and disease progression. The aim of the study was to determine the predictive added value of multimodal SC MRI on survival. Forty-nine ALS patients were recruited and clinical data were collected. Patients were scored on the Revised ALS Functional Rating Scale and manual muscle testing. They were followed longitudinally to assess survival. The cervical SC was imaged using the 3 T MRI system. Cord volume and cross-sectional area (CSA) at each vertebral level were computed. Diffusion tensor imaging metrics were measured. Imaging metrics and clinical variables were used as inputs for a multivariate Cox regression survival model. On building a multivariate Cox regression model with clinical and MRI parameters, fractional anisotropy, magnetization transfer ratio and CSA at C2-C3, C4-C5, C5-C6 and C6-C7 vertebral levels were significant. Moreover, the hazard ratio calculated for CSA at the C3-C4 and C5-C6 levels indicated an increased risk for patients with SC atrophy (respectively 0.66 and 0.68). In our cohort, MRI parameters seem to be more predictive than clinical variables, which had a hazard ratio very close to 1. It is suggested that multimodal SC MRI could be a useful tool in survival prediction especially if used at the beginning of the disease and when combined with clinical variables. To validate it as a biomarker, confirmation of the results in bigger independent cohorts of patients is warranted. © 2017 EAN.

Undernutrition as independent predictor of early mortality in elderly cancer patients.

PubMed

Martucci, Renata B; Barbosa, Mariana V; D'Almeida, Cristiane A; Rodrigues, Viviane D; Bergmann, Anke; de Pinho, Nivaldo B; Thuler, Luiz Claudio S

2017-02-01

The aim of this study was to evaluate the 1-y survival of elderly patients with cancer and the association between undernutrition and mortality. This was a cohort study with elderly patients ages ≥65 y admitted between September and October 2014. A nutritionist performed a Mini Nutritional Assessment-Short Form (MNA-SF) assessment during 48 h of hospital admission and collected data about potential confounding variables (comorbidities, stage of cancer, treatment in the previous 3 mo, and reason for hospitalization). Vital status was determined from the medical records or public records office. Overall survival was estimated using the Kaplan-Meier method. Cox regression was performed to estimate unadjusted hazard ratios. Variables with P < 0.20 by univariate analysis were selected for multivariate analysis. P < 0.05 was considered statistically significant. Of the 136 patients (mean age, 73.1 y; 52.2% men), 29.4%, 41.2%, and 29.4% were classified as normal, at risk for undernutrition, and undernutrition, respectively, according to the MNA-SF. The mortality rate was 31.6% after 12 mo. One-year mortality was higher among the undernourished patients, followed by patients at risk for undernutrition. After adjustment for confounding variables, the multivariate regression Cox model showed that being undernourished according to the MNA-SF increased the risk for death at 1 y (hazard ratio, 5.59; 95% confidence interval, 1.8-17.3; P < 0.001). The results showed that the MNA-SF can be a useful tool in identifying elderly patients at higher risk for 1-y mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum prognostic biomarkers in head and neck cancer patients.

PubMed

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

2014-08-01

A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Serum Prognostic Biomarkers in Head and Neck Cancer Patients

PubMed Central

Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S.; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H.; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J.; Tainsky, Michael A.

2014-01-01

Objectives/Hypothesis A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Study Design Prospective cohort study. Methods A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient’s serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Results Poor overall survival was associated with African Americans (hazard ratio [HR] for death =2.61; 95% confidence interval [CI]: 1.58–4.33; P =.000), advanced stage (HR =2.79; 95% CI: 1.40–5.57; P =.004), and recurrent disease (HR =6.66; 95% CI: 2.54–17.44; P =.000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. Conclusions The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. PMID:24347532

Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

PubMed

Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

2018-04-23

Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial

PubMed Central

2014-01-01

Introduction Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes. Methods We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models. Results Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling. Conclusions In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes. Trial registration ClinicalTrials.gov number, NCT00221013 PMID:24629036

Nomogram Prediction of Overall Survival After Curative Irradiation for Uterine Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, YoungSeok; Yoo, Seong Yul; Kim, Mi-Sook

Purpose: The purpose of this study was to develop a nomogram capable of predicting the probability of 5-year survival after radical radiotherapy (RT) without chemotherapy for uterine cervical cancer. Methods and Materials: We retrospectively analyzed 549 patients that underwent radical RT for uterine cervical cancer between March 1994 and April 2002 at our institution. Multivariate analysis using Cox proportional hazards regression was performed and this Cox model was used as the basis for the devised nomogram. The model was internally validated for discrimination and calibration by bootstrap resampling. Results: By multivariate regression analysis, the model showed that age, hemoglobin levelmore » before RT, Federation Internationale de Gynecologie Obstetrique (FIGO) stage, maximal tumor diameter, lymph node status, and RT dose at Point A significantly predicted overall survival. The survival prediction model demonstrated good calibration and discrimination. The bootstrap-corrected concordance index was 0.67. The predictive ability of the nomogram proved to be superior to FIGO stage (p = 0.01). Conclusions: The devised nomogram offers a significantly better level of discrimination than the FIGO staging system. In particular, it improves predictions of survival probability and could be useful for counseling patients, choosing treatment modalities and schedules, and designing clinical trials. However, before this nomogram is used clinically, it should be externally validated.« less

Does buccal cancer have worse prognosis than other oral cavity cancers?

PubMed

Camilon, P Ryan; Stokes, William A; Fuller, Colin W; Nguyen, Shaun A; Lentsch, Eric J

2014-06-01

To determine whether buccal squamous cell carcinoma has worse overall survival (OS) and disease-specific survival (DSS) than cancers in the rest of the oral cavity. Retrospective analysis of a large population database. We began with a Kaplan-Meier analysis of OS and DSS for buccal versus nonbuccal tumors with unmatched data, followed by an analysis of cases matched for race, age at diagnosis, stage at diagnosis, and treatment modality. This was supported by a univariate Cox regression comparing buccal cancer to nonbuccal cancer, followed by a multivariate Cox regression that included all significant variables studied. With unmatched data, buccal cancer had significantly lesser OS and DSS values than cancers in the rest of the oral cavity (P < .001). After case matching, the differences between OS and DSS for buccal cancer versus nonbuccal oral cancer were no longer significant. Univariate Cox regression models with respect to OS and DSS showed a significant difference between buccal cancer and nonbuccal cancer. However, with multivariate analysis, buccal hazard ratios for OS and DSS were not significant. With the largest series of buccal carcinoma to date, our study concludes that the OS and DSS of buccal cancer are similar to those of cancers in other oral cavity sites once age at diagnosis, tumor stage, treatment, and race are taken into consideration. The previously perceived poor prognosis of buccal carcinoma may be due to variations in tumor presentation, such as later stage and older patient age. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs and 30-day stroke mortality.

PubMed

Schmidt, Morten; Hováth-Puhó, Erzsébet; Christiansen, Christian Fynbo; Petersen, Karin L; Bøtker, Hans Erik; Sørensen, Henrik Toft

2014-11-25

To examine whether preadmission use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) influenced 30-day stroke mortality. We conducted a nationwide population-based cohort study. Using medical databases, we identified all first-time stroke hospitalizations in Denmark between 2004 and 2012 (n = 100,043) and subsequent mortality. We categorized NSAID use as current (prescription redemption within 60 days before hospital admission), former, and nonuse. Current use was further classified as new or long-term use. Cox regression was used to compute hazard ratios (HRs) of death within 30 days, controlling for potential confounding through multivariable adjustment and propensity score matching. The adjusted HR of death for ischemic stroke was 1.19 (95% confidence interval [CI]: 1.02-1.38) for current users of selective cyclooxygenase (COX)-2 inhibitors compared with nonusers, driven by the effect among new users (1.42, 95% CI: 1.14-1.77). Comparing the different COX-2 inhibitors, the HR was driven by new use of older traditional COX-2 inhibitors (1.42, 95% CI: 1.14-1.78) among which it was 1.53 (95% CI: 1.02-2.28) for etodolac and 1.28 (95% CI: 0.98-1.68) for diclofenac. The propensity score-matched analysis supported the association between older COX-2 inhibitors and ischemic stroke mortality. There was no association for former users. Mortality from intracerebral hemorrhage was not associated with use of nonselective NSAIDs or COX-2 inhibitors. Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke. Use of nonselective NSAIDs at time of admission was not associated with mortality from ischemic stroke or intracerebral hemorrhage. © 2014 American Academy of Neurology.

[Study on factors influencing survival in patients with advanced gastric carcinoma after resection by Cox's proportional hazard model].

PubMed

Wang, S; Sun, Z; Wang, S

1996-11-01

A prospective follow-up study of 539 advanced gastric carcinoma patients after resection was undertaken between 1 January 1980 and 31 December 1989, with a follow-up rate of 95.36%. A multivariate analysis of possible factors influencing survival of these patients was performed, and their predicting models of survival rates was established by Cox proportional hazard model. The results showed that the major significant prognostic factors influencing survival of these patients were rate and station of lymph node metastases, type of operation, hepatic metastases, size of tumor, age and location of tumor. The most important factor was the rate of lymph node metastases. According to their regression coefficients, the predicting value (PV) of each patient was calculated, then all patients were divided into five risk groups according to PV, their predicting models of survival rates after resection were established in groups. The goodness-fit of estimated predicting models of survival rates were checked by fitting curve and residual plot, and the estimated models tallied with the actual situation. The results suggest that the patients with advanced gastric cancer after resection without lymph node metastases and hepatic metastases had a better prognosis, and their survival probability may be predicted according to the predicting model of survival rates.

Diagnosis of pernicious anemia and the risk of pancreatic cancer.

PubMed

Shah, Pari; Rhim, Andrew D; Haynes, Kevin; Hwang, Wei-Ting; Yang, Yu-Xiao

2014-04-01

A number of studies have demonstrated a trophic effect of gastrin on pancreatic cancer cells in vitro. Pernicious anemia (PA) is a clinical condition characterized by chronic hypergastrinemia. The aim of this study was to determine if PA is a risk factor for pancreatic cancer. This study is a retrospective cohort study using The Health Improvement Network database, which contains comprehensive health information on 7.5 million patients in the United Kingdom from 1993 to 2009. All patients with PA in the study cohort were identified and composed of the exposed group. Each exposed patient was matched on practice site, sex, and age with up to 4 unexposed patients without PA. The outcome was incident pancreatic cancer. The hazard ratio and 95% confidence intervals were estimated using multivariable Cox regression analysis. We identified 15,324 patients with PA and 55,094 unexposed patients. Mean follow-up time was similar between groups (exposed 4.31 [SD, 3.38] years, unexposed 4.63 [SD, 3.44] years). The multivariable adjusted hazard ratio for pancreatic cancer associated with PA was 1.16 (95% confidence interval, 0.77-1.76; P = 0.47). There is no significant association between PA and the risk of pancreatic cancer.

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

PubMed Central

2010-01-01

Background The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer. Trial Registration Current Controlled Trials: NCT00004205 PMID:20144231

Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: a prospective study.

PubMed

Larsson, Susanna C; Håkanson, Niclas; Permert, Johan; Wolk, Alicja

2006-06-01

High meat consumption has been associated with increased risk of pancreatic cancer in several, although not all, case-control studies. However, prospective data on this relationship are sparse, and the results have been inconsistent. We prospectively evaluated meat, fish, poultry, and egg consumption in relation to pancreatic cancer incidence in a population-based cohort of 61,433 Swedish women. Diet was assessed with a food-frequency questionnaire at baseline (1987-1990) and again in 1997. Pancreatic cancers were ascertained through linkage to the Swedish Cancer Register. Cox proportional hazards models were used to estimate multivariate hazard ratios with 95% confidence intervals (CI). During the 941,218 person-years of follow-up, from 1987 through 2004, 172 incident cases of pancreatic cancer were diagnosed. Long-term red meat consumption (using data from both dietary questionnaires) was positively associated with risk of pancreatic cancer (p-trend = 0.01), whereas long-term poultry consumption was inversely (p-trend = 0.04) associated with risk. The multivariate hazard ratios for the highest versus the lowest category of consumption were 1.73 (95% CI = 0.99-2.98) for red meat and 0.44 (95% CI = 0.20-0.97) for poultry. There were no significant associations with processed meat, fish or egg consumption. Findings from this prospective study suggest that substituting poultry for red meat might reduce the risk of pancreatic cancer.

Similar survival of patients with multiple versus single primary melanomas based on Utah Surveillance, Epidemiology, and End Results data (1973-2011).

PubMed

Grossman, Douglas; Farnham, James M; Hyngstrom, John; Klapperich, Marki E; Secrest, Aaron M; Empey, Sarah; Bowen, Glen M; Wada, David; Andtbacka, Robert H I; Grossmann, Kenneth; Bowles, Tawnya L; Cannon-Albright, Lisa A

2018-03-01

Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). We compared MPM versus SPM patient survival using a matching method that avoids potential biases associated with other analytic approaches. Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End Results registry of all melanomas diagnosed or treated in Utah between 1973 and 2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. Survival curves (n = 887 for both MPM and SPM groups) without covariates showed a significant survival disadvantage for MPM patients (chi-squared 39.29, P < .001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio 1.07, P = .55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio 0.99, P = .96). Breslow depth, ulceration status, and specific cause of death were not available for all patients. Patients with MPM had similar survival times as patients with SPM. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Lung cancer incidence and survival among HIV-infected and uninfected women and men.

PubMed

Hessol, Nancy A; Martínez-Maza, Otoniel; Levine, Alexandra M; Morris, Alison; Margolick, Joseph B; Cohen, Mardge H; Jacobson, Lisa P; Seaberg, Eric C

2015-06-19

To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men. Two longitudinal studies of HIV infection in the United States. Data from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses. Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time. Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

Shear wave elastography predicts hepatocellular carcinoma risk in hepatitis C patients after sustained virological response.

PubMed

Hamada, Koichi; Saitoh, Satoshi; Nishino, Noriyuki; Fukushima, Daizo; Horikawa, Yoshinori; Nishida, Shinya; Honda, Michitaka

2018-01-01

To evaluate the relationship between fibrosis and HCC after sustained virological response (SVR) to treatment for chronic hepatitis C (HCV). This single-center study retrospectively evaluated 196 patients who achieved SVR after HCV infection. The associations of risk factors with HCC development after HCV eradication were evaluated using univariate and multivariate Cox proportional hazards regression models. Among the 196 patients, 8 patients (4.1%) developed HCC after SVR during a median follow-up of 26 months. Multivariate analyses revealed that HCC development was independently associated with age of ≥75 years (risk ratio [RR] = 35.16), α- fetoprotein levels of ≥6 ng/mL (RR = 40.30), and SWE results of ≥11 kPa (RR = 28.71). Our findings indicate that SWE may facilitate HCC surveillance after SVR and the identification of patients who have an increased risk of HCC after HCV clearance.

Cancer Survival Estimates Due to Non-Uniform Loss to Follow-Up and Non-Proportional Hazards

PubMed

K M, Jagathnath Krishna; Mathew, Aleyamma; Sara George, Preethi

2017-06-25

Background: Cancer survival depends on loss to follow-up (LFU) and non-proportional hazards (non-PH). If LFU is high, survival will be over-estimated. If hazard is non-PH, rank tests will provide biased inference and Cox-model will provide biased hazard-ratio. We assessed the bias due to LFU and non-PH factor in cancer survival and provided alternate methods for unbiased inference and hazard-ratio. Materials and Methods: Kaplan-Meier survival were plotted using a realistic breast cancer (BC) data-set, with >40%, 5-year LFU and compared it using another BC data-set with <15%, 5-year LFU to assess the bias in survival due to high LFU. Age at diagnosis of the latter data set was used to illustrate the bias due to a non-PH factor. Log-rank test was employed to assess the bias in p-value and Cox-model was used to assess the bias in hazard-ratio for the non-PH factor. Schoenfeld statistic was used to test the non-PH of age. For the non-PH factor, we employed Renyi statistic for inference and time dependent Cox-model for hazard-ratio. Results: Five-year BC survival was 69% (SE: 1.1%) vs. 90% (SE: 0.7%) for data with low vs. high LFU respectively. Age (<45, 46-54 & >54 years) was a non-PH factor (p-value: 0.036). However, survival by age was significant (log-rank p-value: 0.026), but not significant using Renyi statistic (p=0.067). Hazard ratio (HR) for age using Cox-model was 1.012 (95%CI: 1.004 -1.019) and the same using time-dependent Cox-model was in the other direction (HR: 0.997; 95% CI: 0.997- 0.998). Conclusion: Over-estimated survival was observed for cancer with high LFU. Log-rank statistic and Cox-model provided biased results for non-PH factor. For data with non-PH factors, Renyi statistic and time dependent Cox-model can be used as alternate methods to obtain unbiased inference and estimates. Creative Commons Attribution License

Skin autofluorescence and all-cause mortality in stage 3 CKD.

PubMed

Fraser, Simon D S; Roderick, Paul J; McIntyre, Natasha J; Harris, Scott; McIntyre, Christopher W; Fluck, Richard J; Taal, Maarten W

2014-08-07

Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied. A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling for biochemistry, and measurement of skin autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality. In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P<0.001) on Kaplan-Meier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P<0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin. Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD. Copyright © 2014 by the American Society of Nephrology.

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

PubMed

Ariyamuthu, Venkatesh K; Amin, Alpesh A; Drazner, Mark H; Araj, Faris; Mammen, Pradeep P A; Ayvaci, Mehmet; Mete, Mutlu; Ozay, Fatih; Ghanta, Mythili; Mohan, Sumit; Mohan, Prince; Tanriover, Bekir

2018-05-01

Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up. During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71). r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Factor VII and incidence of myocardial infarction in a Japanese population: The Jichi Medical School Cohort Study.

PubMed

Shiraishi, Takuya; Ishikawa, Shizukiyo; Kario, Kazuomi; Kayaba, Kazunori; Kajii, Eiji

2017-11-01

The role of factor VII (FVII) as a risk factor in myocardial infarction (MI) has been the subject of numerous studies. However, it remains uncertain whether the FVII levels are associated with development of MI. The subjects were 4142 men and women whose activated FVII (FVIIa) and FVII coagulant (FVIIc) levels were measured in the Jichi Medical School Cohort Study. Subjects were divided into tertiles by FVIIa and FVIIc levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for MI. The multivariate-adjusted HRs (95% confidential interval [CI]) for FVIIa in men were 0.67 (0.67-1.78) in tertile 2 (T2), and 0.52 (0.17-1.60) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.18 (0.02-1.60) in T2, and 0.39 (0.07-2.20) in T3. The multivariate-adjusted HRs (95% CI) for FVIIc in men were 0.54 (0.21-1.36) in T2, and 0.20 (0.04-0.91) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.44 (0.07-2.85) in T2, and 0.35 (0.06-2.22) in T3. We used T1 as a reference for all measures. Our findings revealed a significant association between low FVIIc level and incidence of MI in men. The FVIIa and FVIIc levels were inversely related to increased MI risk, but did not reach statistical significance. Future studies are needed to confirm this association. © 2017 Wiley Periodicals, Inc.

Differences in neurohormonal activity partially explain the obesity paradox in patients with heart failure: The role of sympathetic activation.

PubMed

Farré, Núria; Aranyó, Júlia; Enjuanes, Cristina; Verdú-Rotellar, José María; Ruiz, Sonia; Gonzalez-Robledo, Gina; Meroño, Oona; de Ramon, Marta; Moliner, Pedro; Bruguera, Jordi; Comin-Colet, Josep

2015-02-15

Obese patients with chronic Heart Failure (HF) have better outcome than their lean counterparts, although little is known about the pathophysiology of this obesity paradox. Our aim was to evaluate the hypothesis that patients with chronic HF and obesity (defined as body mass index (BMI)≥30kg/m(2)), may have an attenuated neurohormonal activation in comparison with non-obese patients. The present study is the post-hoc analysis of a cohort of 742 chronic HF patients from a single-center study evaluating sympathetic activation by measuring baseline levels of norepinephrine (NE). Obesity was present in 33% of patients. Higher BMI and obesity were significantly associated with lower NE levels in multivariable linear regression models adjusted for covariates (p<0.001). Addition to NE in multivariate Cox proportional hazard models attenuated the prognostic impact of BMI in terms of outcomes. Finally, when we explored the prognosis impact of raised NE levels (>70th percentile) carrying out a separate analysis in obese and non-obese patients we found that in both groups NE remained a significant independent predictor of poorer outcomes, despite the lower NE levels in patients with chronic HF and obesity: all-cause mortality hazard ratio=2.37 (95% confidence interval, 1.14-4.94) and hazard ratio=1.59 (95% confidence interval, 1.05-2.4) in obese and non-obese respectively; and cardiovascular mortality hazard ratio=3.08 (95% confidence interval, 1.05-9.01) in obese patients and hazard ratio=2.08 (95% confidence interval, 1.42-3.05) in non-obese patients. Patients with chronic HF and obesity have significantly lower sympathetic activation. This finding may partially explain the obesity paradox described in chronic HF patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis.

PubMed

Gunia, Sven; Kakies, Christoph; Erbersdobler, Andreas; Hakenberg, Oliver W; Koch, Stefan; May, Matthias

2012-03-01

To evaluate the role of p53, p21 and cyclin D1 expression in patients with penile cancer (PC). Paraffin-embedded tissues from PC specimens from six pathology departments were subjected to a central histopathological review performed by one pathologist. The tissue microarray technique was used for immunostaining which was evaluated by two independent pathologists and correlated with cancer-specific survival (CSS). κ-statistics were used to assess interobserver variability. Uni- and multivariable Cox proportional hazards analysis was applied to assess the independent effects of several prognostic factors on CSS over a median of 32 months (IQR 6-66 months). Specimens and clinical data from 110 men treated surgically for primary PC were collected. p53 staining was positive in 30 and negative in 62 specimens. κ-statistics showed substantial interobserver reproducibility of p53 staining evaluation (κ=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%. Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin D1 and p21 expression were not correlated with survival. However, incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting CSS. In patients with PC, the expression of p53 in the primary tumour specimen can be reproducibly assessed and is negatively associated with cancer specific survival.

Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy

PubMed Central

Kriege, M; Hollestelle, A; Jager, A; Huijts, P E A; Berns, E M; Sieuwerts, A M; Meijer-van Gelder, M E; Collée, J M; Devilee, P; Hooning, M J; Martens, J W M; Seynaeve, C

2014-01-01

Background: We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. Methods: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. Results: The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59–6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79–3.93) and 2.05 (1.41–2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. Conclusions: The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients. PMID:24918820

Non-Steroidal Anti-Inflammatory Drugs and Cardiovascular Outcomes in Women: Results from the Women’s Health Initiative

PubMed Central

Bavry, Anthony A.; Thomas, Fridtjof; Allison, Matthew; Johnson, Karen C.; Howard, Barbara V.; Hlatky, Mark; Manson, JoAnn E.; Limacher, Marian C.

2014-01-01

Background Conclusive data regarding cardiovascular (CV) toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for CV events in post-menopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 compared with cox-1 inhibition. Methods and Results Post-menopausal women enrolled in the Women’s Health Initiative (WHI) were classified as regular users or non-users of non-aspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total CV disease defined as CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (e.g., celecoxib), non-selective agents with cox-2>cox-1 inhibition (e.g., naproxen), and non-selective agents with cox-1>cox-2 inhibition (e.g., ibuprofen) with the primary outcome. Overall, 160,801 participants were available for analysis (mean follow-up 11.2 years). Regular NSAID use at some point in time was reported by 53,142 participants. Regular NSAID use was associated with an increased hazard for CV events versus no NSAID use (HR=1.10[95% CI 1.06–1.15], Pitalic>0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for CV events (HR=1.13[1.04–1.23], P=0.004; celecoxib only HR=1.13[1.01–1.27], P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for CV events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR=1.17[1.10–1.24], Pbold>0.001; naproxen only HR=1.22[1.12–1.34], P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR=1.01[0.95–1.07], P=0.884; ibuprofen only HR=1.00[0.93–1.07], P=0.996). Conclusions Regular use of selective cox-2 inhibitors and non-selective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for CV events. Non-selective agents with cox-1>cox-2 inhibition were not associated with increased CV risk. Clinical Trial Registration www.clinicaltrials.gov NCT00000611 PMID:25006185

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

Koh, Kyoung Hwan; Cho, Eun Yoon; Kim, Dong Wook; Seo, Sung Wook

2009-11-01

Many studies have described the diversity of synovial sarcoma in terms of its biological characteristics and clinical features. Moreover, much effort has been expended on the identification of prognostic factors because of unpredictable behaviors of synovial sarcomas. However, with the exception of tumor size, published results have been inconsistent. We attempted to identify independent risk factors using survival analysis. Forty-one consecutive patients with synovial sarcoma were prospectively followed from January 1997 to March 2008. Overall and progression-free survival for age, sex, tumor size, tumor location, metastasis at presentation, histologic subtype, chemotherapy, radiation therapy, and resection margin were analyzed, and standard multivariate Cox proportional hazard regression analysis was used to evaluate potential prognostic factors. Tumor size (>5 cm), nonlimb-based tumors, metastasis at presentation, and a monophasic subtype were associated with poorer overall survival. Multivariate analysis showed metastasis at presentation and monophasic tumor subtype affected overall survival. For the progression-free survival, monophasic subtype was found to be only 1 prognostic factor. The study confirmed that histologic subtype is the single most important independent prognostic factors of synovial sarcoma regardless of tumor stage.

Timing of Adjuvant Surgical Oophorectomy in the Menstrual Cycle and Disease-Free and Overall Survival in Premenopausal Women With Operable Breast Cancer

PubMed Central

Laudico, Adriano V.; Van Dinh, Nguyen; Allred, D. Craig; Uy, Gemma B.; Quang, Le Hong; Salvador, Jonathan Disraeli S.; Siguan, Stephen Sixto S.; Mirasol-Lumague, Maria Rica; Tung, Nguyen Dinh; Benjaafar, Noureddine; Navarro, Narciso S.; Quy, Tran Tu; De La Peña, Arturo S.; Dofitas, Rodney B.; Bisquera, Orlino C.; Linh, Nguyen Dieu; To, Ta Van; Young, Gregory S.; Hade, Erinn M.; Jarjoura, David

2015-01-01

Background: For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. Methods: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. Results: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. Conclusions: The hypothesized benefit of adjuvant luteal phase oophorectomy was not shown in this large trial. PMID:25794890

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study.

PubMed

Matsumoto, Kazumasa; Novara, Giacomo; Gupta, Amit; Margulis, Vitaly; Walton, Thomas J; Roscigno, Marco; Ng, Casey; Kikuchi, Eiji; Zigeuner, Richard; Kassouf, Wassim; Fritsche, Hans-Martin; Ficarra, Vincenzo; Martignoni, Guido; Tritschler, Stefan; Rodriguez, Joaquin Carballido; Seitz, Christian; Weizer, Alon; Remzi, Mesut; Raman, Jay D; Bolenz, Christian; Bensalah, Karim; Koppie, Theresa M; Karakiewicz, Pierre I; Wood, Christopher G; Montorsi, Francesco; Iwamura, Masatsugu; Shariat, Shahrokh F

2011-10-01

•To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU). •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908). •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Prognostic Value of Pretherapeutic Tumor-to-Blood Standardized Uptake Ratio in Patients with Esophageal Carcinoma.

PubMed

Bütof, Rebecca; Hofheinz, Frank; Zöphel, Klaus; Stadelmann, Tobias; Schmollack, Julia; Jentsch, Christina; Löck, Steffen; Kotzerke, Jörg; Baumann, Michael; van den Hoff, Jörg

2015-08-01

Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Risk factors for keratinocyte skin cancer in patients diagnosed with melanoma, a large retrospective study.

PubMed

Espinosa, Pablo; Pfeiffer, Ruth M; García-Casado, Zaida; Requena, Celia; Landi, Maria Teresa; Kumar, Rajiv; Nagore, Eduardo

2016-01-01

Melanoma survivors are at an increased risk of developing other malignancies, including keratinocyte skin cancer (KSC). While it is known that many risk factors for melanoma also impact risk of KSC in the general population, no previous study has investigated risk factors for KSC development in melanoma patients. We assessed associations of personal and clinical characteristics, including skin phenotype and variations in the melanocortin 1 receptor (MC1R) gene, with KSC risk in melanoma patients. We used prospective follow-up information on 1200 patients treated for melanoma at the Instituto Valenciano de Oncología, Spain, between 2000 and 2011. We computed hazard ratios and 95% confidence intervals (CIs) for the association of clinical, personal and genetic characteristics with risk of KSC, squamous cell carcinoma (SCC), or basal cell carcinoma (BCC) from Cox proportional hazard models. Five-year cumulative incidence based on competing risk models of SCC, BCC or KSC overall was computed using multivariate subdistribution hazard models. To assess predictive performance of the models, we computed areas under the receiver-operating characteristic curves (AUCs, discriminatory power) using cross-validation. Median follow-up was 57.2 months; a KSC was detected in 163 patients (13.6%). In multivariable Cox models, age, sex, sunburns, chronic sun exposure, past personal history of non-melanoma skin cancer or other non-cutaneous neoplasia, and the MC1R variants p.D294H and p.R163Q were significantly associated with KSC risk. A cumulative incidence model including age, sex, personal history of KSC, and of other non-cutaneous neoplasia had an AUC of 0.76 (95% CI: 0.71-0.80). When p.D294H and p.R163Q variants were added to the model, the AUC increased to 0.81 (95% CI: 0.77-0.84) (p-value for difference <0.0001). In addition to age, sex, skin characteristics, and sun exposure, p.R163Q and p.D294H MC1R variants significantly increased KSC risk among melanoma patients. Our findings may help identify patients who could benefit most from preventive measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Jiayi; Vicini, Frank A.; Williams, Scott G.

2012-07-15

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleasonmore » score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.« less

Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease.

PubMed

Zhou, Bing-Yang; Guo, Yuan-Lin; Wu, Na-Qiong; Zhu, Cheng-Gang; Gao, Ying; Qing, Ping; Li, Xiao-Lin; Wang, Yao; Dong, Qian; Liu, Geng; Xu, Rui Xia; Cui, Chuan-Jue; Sun, Jing; Li, Jian-Jun

2017-03-01

Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear. A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016). The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Usefulness of admission gamma-glutamyltransferase level for predicting new-onset heart failure in patients with acute coronary syndrome with left ventricular systolic dysfunction.

PubMed

Sarıkaya, Savaş; Aydın, Gülay; Yücel, Hasan; Kaya, Hakkı; Yıldırımlı, Kutay; Başaran, Ahmet; Zorlu, Ali; Sahin, Safak; Akyol, Lütfü; Bulut, Musa

2014-04-01

Our aim was to determine whether there is a relationship between admission gamma-glutamyltransferase (GGT) and subsequent heart failure hospitalizations in patients with acute coronary syndrome. We selected 123 patients with newly diagnosed acute coronary syndrome of ejection fraction (EF) <45%. Patients were followed 15±10 months, and the relationship between admission GGT level and hospitalization because of heart failure during the follow-up was examined. Twenty-three (18.7%) patients were hospitalized during the follow-up of 15±10 months. Receiver operating characteristic (ROC) curve analysis showed that the cut-off point of admission GGT related to predict hospitalization was 49 IU/L, with a sensitivity of 81.7% and specificity of 65.2%. Increased GGT >49 IU/L on admission, presence of hypertension and hyperlipidemia, left ventricular ejection fraction (LVEF), right ventricular dysfunction, moderate-to-severe mitral regurgitation, alanine aminotransferase level, and antiplatelet agent usage were found to have prognostic significance in univariate Cox proportional hazards analysis. In multivariate Cox proportional-hazards model, increased GGT >49 IU/L on admission (hazard ratio [HR] 2.663, p=0.047), presence of hypertension (HR 4.107, p=0.007), and LVEF (HR 0.911, p=0.002) were found to be independent factors to predict new-onset heart failure requiring hospitalization. Hospitalization in heart failure was associated with increased admission GGT levels. Increased admission GGT level in acute coronary syndrome with heart failure should be monitored closely and treated aggressively.

C-reactive protein as an adverse prognostic marker for men with castration-resistant prostate cancer (CRPC): confirmatory results

PubMed Central

Prins, Renee C.; Rademacher, Brooks L.; Mongoue-Tchokote, Solange; Alumkal, Joshi J.; Graff, Julie N.; Eilers, Kristine M.; Beer, Tomasz M.

2010-01-01

We previously reported that higher serum concentrations of C-reactive protein (CRP) are associated with shorter survival in men with castration-resistant prostate cancer (CRPC). To confirm this finding in an independent data set, we used 119 CRPC patients enrolled in 6 phase II clinical trials and examined the relationship of CRP, alkaline phosphatase, hemoglobin, age, ECOG PS, and prostate specific antigen (PSA) with survival. Median follow-up was 19.7 months (0.9–98.5 months) and 89% have died. After analyzing the form of the risk function using the generalized additive model method, univariate and multivariate Cox proportional hazard models were used to assess associations between baseline individual categorical and continuous variables. Quartiles of CRP were: 1: 0–1.0, 1.1–4.9, 5.0–17.0, and 17.1 to 311 mg/L. In a Cox multivariate model, log2(CRP) (HR 1.106 p=0.013) as well as hemoglobin and alkaline phosphatase were independently associated with survival, confirming that higher CRP is associated with shorter survival in CRPC. Since CRP is a marker of inflammation, this finding suggests that inflammation may play an important role in the natural history of advanced prostate cancer. CRP is a readily measurable biomarker that has the potential to improve prognostic models and should be validated in a prospective clinical trial. PMID:20207556

Analysis of risk factors for central venous port failure in cancer patients

PubMed Central

Hsieh, Ching-Chuan; Weng, Hsu-Huei; Huang, Wen-Shih; Wang, Wen-Ke; Kao, Chiung-Lun; Lu, Ming-Shian; Wang, Chia-Siu

2009-01-01

AIM: To analyze the risk factors for central port failure in cancer patients administered chemotherapy, using univariate and multivariate analyses. METHODS: A total of 1348 totally implantable venous access devices (TIVADs) were implanted into 1280 cancer patients in this cohort study. A Cox proportional hazard model was applied to analyze risk factors for failure of TIVADs. Log-rank test was used to compare actuarial survival rates. Infection, thrombosis, and surgical complication rates (χ2 test or Fisher’s exact test) were compared in relation to the risk factors. RESULTS: Increasing age, male gender and open-ended catheter use were significant risk factors reducing survival of TIVADs as determined by univariate and multivariate analyses. Hematogenous malignancy decreased the survival time of TIVADs; this reduction was not statistically significant by univariate analysis [hazard ratio (HR) = 1.336, 95% CI: 0.966-1.849, P = 0.080)]. However, it became a significant risk factor by multivariate analysis (HR = 1.499, 95% CI: 1.079-2.083, P = 0.016) when correlated with variables of age, sex and catheter type. Close-ended (Groshong) catheters had a lower thrombosis rate than open-ended catheters (2.5% vs 5%, P = 0.015). Hematogenous malignancy had higher infection rates than solid malignancy (10.5% vs 2.5%, P < 0.001). CONCLUSION: Increasing age, male gender, open-ended catheters and hematogenous malignancy were risk factors for TIVAD failure. Close-ended catheters had lower thrombosis rates and hematogenous malignancy had higher infection rates. PMID:19787834

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

PubMed

Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

PubMed Central

Ma, Wen-Juan; Wang, Xing; Yan, Wen-Ting; Zhou, Zhong-Guo; Pan, Zhi-Zhong; Chen, Gong; Zhang, Rong-Xin

2018-01-01

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 (IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer (CRC) patients. METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival (OS) outcomes. RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index (P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1 (P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio (HR) = 2.044, 95% confidence interval (CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2 (HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2 (HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1 (P = 0.041), nuclear/cytoplasmic IDO1 (HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2 (HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC (HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients (HR = 3.210, 95%CI: 1.074-9.590, P = 0.037). CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC. PMID:29853736

Risk Factors for Upper Gastrointestinal Bleeding in Patients Taking Selective COX-2 Inhibitors: A Nationwide Population-Based Cohort Study.

PubMed

Lin, Xi-Hsuan; Young, Shih-Hao; Luo, Jiing-Chyuan; Peng, Yen-Ling; Chen, Ping-Hsien; Lin, Chung-Chi; Chen, Wei-Ming; Hou, Ming-Chih; Lee, Fa-Yauh

2018-02-01

Cyclooxygenase-2 inhibitors (coxibs) are associated with less upper gastrointestinal bleeding (UGIB) than traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, they also increase the risk of UGIB in high-risk patients. We aimed to identify the risk factors of UGIB in coxibs users. Retrospective cohort study. 2000-2010 National Health Insurance Research Database of Taiwan. Patients taking coxibs as the study group and patients not taking any coxibs as controls. After age, gender, and comorbidity matching by propensity score, 12,145 coxibs users and 12,145 matched controls were extracted for analysis. The primary end point was the occurrence of UGIB. Cox multivariate proportional hazard regression models were used to determine the risk factors for UGIB among all the enrollees and coxibs users. During a mean follow-up of three years, coxibs users had significantly higher incidence of UGIB than matched controls (P < 0.001, log-rank test). Cox regression analysis showed that coxibs increased risk of UGIB in all participants (hazard ratio = 1.37, 95% confidence interval = 1.19-1.55, P < 0.001). Independent risk factors for UGIB among coxibs users were age, male gender, diabetes, chronic renal disease, cirrhosis, history of peptic ulcer disease, PU bleeding (PUB), Helicobacter pylori (H. pylori) infection, and concomitant use of tNSAIDs, acetylsalicylic acid, or thienopyridines. Among coxibs users, H. pylori infection and history of PUB were especially important risk factors for UGIB. Further studies are needed to determine whether proton pump inhibitors might play a protective role in these at-risk patients. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort.

PubMed

López-Cortés, L E; Almirante, B; Cuenca-Estrella, M; Garnacho-Montero, J; Padilla, B; Puig-Asensio, M; Ruiz-Camps, I; Rodríguez-Baño, J

2016-08-01

We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The impact of non-fatal workplace injuries and illnesses on mortality.

PubMed

Boden, Leslie I; O'Leary, Paul K; Applebaum, Katie M; Tripodis, Yorghos

2016-12-01

Little research has examined the relationship between non-fatal workplace injuries and illnesses, and long-term mortality. We linked non-fatal injury cases reported to the New Mexico workers' compensation system for 1994-2000 with Social Security Administration data on individual earnings and mortality through 2014. We then derived sex-specific Kaplan-Meier curves to show time to death for workers with lost-time injuries (n = 36,377) and comparison workers (n = 70,951). We fit multivariable Cox survival models to estimate the hazard ratio separately for male and female workers with lost-time injuries. The estimated hazard ratio for lost-time injuries is 1.24 for women and 1.21 for men. Ninety-five percent confidence intervals were 1.15, 1.35 and 1.15, 1.27, respectively. Lost-time occupational injuries are associated with a substantially elevated mortality hazard. This implies an important formerly unmeasured cost of these injuries and a further reason to focus on preventing them. Am. J. Ind. Med. 59:1061-1069, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Utility and direct costs: ankylosing spondylitis compared with rheumatoid arthritis.

PubMed

Verstappen, S M M; Jacobs, J W G; van der Heijde, D M; van der Linden, Sj; Verhoef, C M; Bijlsma, J W J; Boonen, A

2007-06-01

To compare utility and disease-specific direct costs between patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) in the Netherlands. Patients with AS and those with RA completed questions on disease characteristics, the EuroQol-5D (EQ-5D) to assess utility, and questionnaire resource utilisation. Resource utilisation was assessed prospectively in AS, but retrospectively in RA. True cost estimates (2003) were used to calculate the costs. Differences in disease characteristics between AS and RA were described, and determinants of EQ-5D utility and costs were explored by Cox proportional hazard regressions. 576 patients with RA and 132 with AS completed the questionnaires. EQ-5D utility (0.63 vs 0.7) was lower, and annual direct costs higher in RA (euro5167 vs euro2574). In multivariate Cox proportional hazard regressions, there was no difference in utility between the diagnostic groups, but patients with RA incurred higher direct costs after controlling for age, gender and disease duration. In patients with RA and patients with AS, who are under the care of a rheumatologist, utility is equally reduced, but healthcare costs are higher in RA after controlling for age, gender and disease duration. These data can be helpful to provide insights into the differences and similarities between the healthcare needs of both patient groups and to identify issues for further research and for policy in healthcare organisations.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

Biologic and social determinants of sequelae and long-term survival of pediatric HIV in Romania.

PubMed

Kozinetz, Claudia A; Matusa, Rodica; Hacker, Carl S

2006-08-01

The aim of the study is to investigate the effect of social context and clinical factors on survival in a cohort of 333 children to identify issues useful in the treatment and care of human immunodeficiency virus (HIV)-infected youth in developing countries. A prospective cohort study design was used, and data were gathered at baseline and 1-year follow-up. The study cohort consisted of children given a diagnosis of HIV between 1995 and 1999 and receiving medical care in Constanta, Romania. Data were examined by means of multivariate Cox regression analysis models. The majority of the cohort were in the moderate (41%) or severe (40%) stages of HIV at baseline. Multivariate analysis indicated that social-context factors were the most significant determinants of HIV survival. The hazard for death for those with mothers or fathers with a higher level of education was approximately one quarter (relative hazard, 0.3-0.4; confidence interval, 0.1-1.0) that for a parent with a lower level of education. Subjects with employed mothers were four times more likely to survive than subjects with unemployed mothers. Results suggest that recognition of social-context risk factors for HIV disease progression and survival is important in developing countries, as it is in developed countries.

Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia.

PubMed

De Stefano, Valerio; Za, Tommaso; Rossi, Elena; Vannucchi, Alessandro M; Ruggeri, Marco; Elli, Elena; Micò, Caterina; Tieghi, Alessia; Cacciola, Rossella R; Santoro, Cristina; Gerli, Giancarla; Guglielmelli, Paola; Pieri, Lisa; Scognamiglio, Francesca; Rodeghiero, Francesco; Pogliani, Enrico M; Finazzi, Guido; Gugliotta, Luigi; Leone, Giuseppe; Barbui, Tiziano

2010-02-01

There is evidence that leukocytosis is associated with an increased risk of first thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrent thrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of a first arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who were not receiving cytoreduction at the time of thrombosis. The probability of recurrent thrombosis associated with the leukocyte count recorded at the time of the first thrombosis was estimated by a receiver operating characteristic analysis and a multivariable Cox proportional hazards regression model. Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12-4.18) in patients with a leukocyte count that was >12.4 x 10(9)/L at the time of the first thrombotic episode. The prognostic role for leukocytosis was age-related, as it was only significant in patients that were aged <60 years (HR for arterial recurrence 3.35, 95% CI 1.22-9.19).

Disparities in breast cancer surgery delay: the lingering effect of race.

PubMed

Sheppard, Vanessa B; Oppong, Bridget A; Hampton, Regina; Snead, Felicia; Horton, Sara; Hirpa, Fikru; Brathwaite, Echo J; Makambi, Kepher; Onyewu, S; Boisvert, Marc; Willey, Shawna

2015-09-01

Delays to surgical breast cancer treatment of 90 days or more may be associated with greater stage migration. We investigated racial disparities in time to receiving first surgical treatment in breast cancer patients. Insured black (56 %) and white (44 %) women with primary breast cancer completed telephone interviews regarding psychosocial (e.g., self-efficacy) and health care factors (e.g., communication). Clinical data were extracted from medical charts. Time to surgery was measured as the days between diagnosis and definitive surgical treatment. We also examined delays of more than 90 days. Unadjusted hazard ratios (HRs) examined univariate relationships between delay outcomes and covariates. Cox proportional hazard models were used for multivariate analyses. Mean time to surgery was higher in blacks (mean 47 days) than whites (mean 33 days; p = .001). Black women were less likely to receive therapy before 90 days compared to white women after adjustment for covariates (HR .58; 95 % confidence interval .44, .78). Health care process factors were nonsignificant in multivariate models. Women with shorter delay reported Internet use (vs. not) and underwent breast-conserving surgery (vs. mastectomy) (p < .01). Prolonged delays to definitive breast cancer surgery persist among black women. Because the 90-day interval has been associated with poorer outcomes, interventions to address delay are needed.

Angiotensin-converting Enzyme Inhibitor and Statin Medication Use and Incident Mobility Limitation in Community Older Adults. The Health, Aging and Body Composition Study

PubMed Central

Gray, Shelly L.; Boudreau, Robert M.; Newman, Anne B.; Studenski, Stephanie A.; Shorr, Ronald I; Bauer, Douglas C.; Simonsick, Eleanor M.; Hanlon, Joseph T

2012-01-01

Objective Angiotensin-converting enzyme (ACE) inhibitors and statin medications have been proposed as potential agents to prevent or delay physical disability; yet limited research has evaluated whether such use in older community dwelling adults is associated with a lower risk of incident mobility limitation. Design Longitudinal cohort study Setting Health, Aging and Body Composition (Health ABC) Participants 3055 participants who were well functioning at baseline (e.g., no mobility limitations). Measurements Summated standardized daily doses (low, medium and high) and duration of ACE inhibitor and statin use was computed. Mobility limitation (two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health status, and health behaviors. Results At baseline, ACE inhibitors and statins were used by 15.2% and 12.9%, respectively and both increased to over 25% by year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.82–1.09) nor statin use (multivariate HR 1.02; 95% CI 0.87–1.17) was associated with a lower risk for mobility limitation. Similar findings were seen in analyses examining dose- and duration-response relationships and sensitivity analyses restricted to those with hypertension. Conclusions These findings indicate that ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively do not lower risk of mobility limitation, an important life quality indicator. PMID:22092102

Alcohol Intake and Risk of Incident Melanoma: A Pooled Analysis of Three Prospective Studies in the U.S

PubMed Central

Rivera, Andrew; Nan, Hongmei; Li, Tricia; Qureshi, Abrar; Cho, Eunyoung

2016-01-01

Background Alcohol consumption is associated with increased risk of numerous cancers, but existing evidence for an association with melanoma is equivocal. No study has evaluated the association with different anatomic locations of melanoma. Methods We used data from three large prospective cohort studies to investigate whether alcohol intake was associated with risk of melanoma. Alcohol intake was assessed repeatedly by food-frequency questionnaires. A Cox proportional hazards model was used to calculate multivariate-adjusted hazard ratios (HRs). Results A total of 1,374 cases of invasive melanoma were documented during 3,855,706 person-years of follow-up. There was an association between higher alcohol intake and incidence of invasive melanoma (pooled multivariate HR 1.14; 95% confidence interval [CI]: 1.00–1.29] per drink/d, p trend = 0.04). Among alcoholic beverages, white wine consumption was associated with an increased risk of melanoma (pooled multivariate HR 1.13 [95% CI: 1.04–1.24] per drink/d, p trend <0.01) after adjusting for other alcoholic beverages. The association between alcohol consumption and melanoma risk was stronger for melanoma in relatively UV-spared sites (trunk) versus more UV-exposed sites (head, neck, or extremities). Compared to non-drinkers, the pooled multivariate-adjusted HRs for ≥20g/d of alcohol were 1.02 (95% CI: 0.64–1.62; P trend =0.25) for melanomas of the head, neck, and extremities and 1.73 (95% CI: 1.25–2.38; P trend =0.02) for melanomas of the trunk. Conclusions Alcohol intake was associated with a modest increase in the risk of melanoma, particularly in UV-protected sites. Impact These findings further support American Cancer Society Guidelines for Cancer Prevention to limit alcohol intake. PMID:27909090

THE AFRICAN DESCENT AND GLAUCOMA EVALUATION STUDY (ADAGES): PREDICTORS OF VISUAL FIELD DAMAGE IN GLAUCOMA SUSPECTS

PubMed Central

Khachatryan, Naira; Medeiros, Felipe A.; Sharpsten, Lucie; Bowd, Christopher; Sample, Pamela A.; Liebmann, Jeffrey M.; Girkin, Christopher A.; Weinreb, Robert N.; Miki, Atsuya; Hammel, Na’ama; Zangwill, Linda M.

2015-01-01

Purpose To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects. Design Prospective, observational cohort study. Methods Six hundred thirty six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox Proportional Hazard models. Results Thirty one (25.4%) of 122 African descent participants and 47 (20.0%) of 235 European descent participants developed VF damage (p=0.078). In multivariable analysis, worse baseline VF mean deviation, higher mean arterial pressure during follow up, and a race *mean intraocular pressure (IOP) interaction term were significantly associated with the development of VF damage suggesting that racial differences in the risk of VF damage varied by IOP. At higher mean IOP levels, race was predictive of the development of VF damage even after adjusting for potentially confounding factors. At mean IOPs during follow-up of 22, 24 and 26 mmHg, multivariable hazard ratios (95%CI) for the development of VF damage in African descent compared to European descent subjects were 2.03 (1.15–3.57), 2.71 (1.39–5.29), and 3.61 (1.61–8.08), respectively. However, at lower mean IOP levels (below 22 mmHg) during follow-up, African descent was not predictive of the development of VF damage. Conclusion In this cohort of glaucoma suspects with similar access to treatment, multivariate analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop VF damage than individuals of European descent. PMID:25597839

Angiotensin-converting enzyme inhibitor and statin use and incident mobility limitation in community-dwelling older adults: the Health, Aging and Body Composition study.

PubMed

Gray, Shelly L; Boudreau, Robert M; Newman, Anne B; Studenski, Stephanie A; Shorr, Ronald I; Bauer, Douglas C; Simonsick, Eleanor M; Hanlon, Joseph T

2011-12-01

To evaluate whether the use of angiotensin-converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. Longitudinal cohort study. Health, Aging and Body Composition (Health ABC) study. Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

[Value of the albumin to globulin ratio in predicting severity and prognosis in myasthenia gravis patients].

PubMed

Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X

2016-03-08

To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR <1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR>1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P<0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P<0.001) and MGFA clinical classification (P<0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P<0.001) and MGFA clinical classification were related to myasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.

Cardiovascular mortality prediction in veterans with arm exercise vs pharmacologic myocardial perfusion imaging.

PubMed

Martin, Wade H; Xian, Hong; Chandiramani, Pooja; Bainter, Emily; Klein, Andrew J P

2015-08-01

No data exist comparing outcome prediction from arm exercise vs pharmacologic myocardial perfusion imaging (MPI) stress test variables in patients unable to perform treadmill exercise. In this retrospective study, 2,173 consecutive lower extremity disabled veterans aged 65.4 ± 11.0years (mean ± SD) underwent either pharmacologic MPI (1730 patients) or arm exercise stress tests (443 patients) with MPI (n = 253) or electrocardiography alone (n = 190) between 1997 and 2002. Cox multivariate regression models and reclassification analysis by integrated discrimination improvement (IDI) were used to characterize stress test and MPI predictors of cardiovascular mortality at ≥10-year follow-up after inclusion of significant demographic, clinical, and other variables. Cardiovascular death occurred in 561 pharmacologic MPI and 102 arm exercise participants. Multivariate-adjusted cardiovascular mortality was predicted by arm exercise resting metabolic equivalents (hazard ratio [HR] 0.52, 95% CI 0.39-0.69, P < .001), 1-minute heart rate recovery (HR 0.61, 95% CI 0.44-0.86, P < .001), and pharmacologic and arm exercise delta (peak-rest) heart rate (both P < .001). Only an abnormal arm exercise MPI prognosticated cardiovascular death by multivariate Cox analysis (HR 1.98, 95% CI 1.04-3.77, P < .05). Arm exercise MPI defect number, type, and size provided IDI over covariates for prediction of cardiovascular mortality (IDI = 0.074-0.097). Only pharmacologic defect size prognosticated cardiovascular mortality (IDI = 0.022). Arm exercise capacity, heart rate recovery, and pharmacologic and arm exercise heart rate responses are robust predictors of cardiovascular mortality. Arm exercise MPI results are equivalent and possibly superior to pharmacologic MPI for cardiovascular mortality prediction in patients unable to perform treadmill exercise. Published by Elsevier Inc.

Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on Long-Term Survival.

PubMed

Scrutinio, Domenico; Monitillo, Vincenzo; Guida, Pietro; Nardulli, Roberto; Multari, Vincenzo; Monitillo, Francesco; Calabrese, Gianluigi; Fiore, Pietro

2015-10-01

Prediction of functional outcome after stroke rehabilitation (SR) is a growing field of interest. The association between SR and survival still remains elusive. We sought to investigate the factors associated with functional outcome after SR and whether the magnitude of functional improvement achieved with rehabilitation is associated with long-term mortality risk. The study population consisted of 722 patients admitted for SR within 90 days of stroke onset, with an admission functional independence measure (FIM) score of <80 points. We used univariable and multivariable linear regression analyses to assess the association between baseline variables and FIM gain and univariable and multivariable Cox analyses to assess the association of FIM gain with long-term mortality. Age (P<0.001), marital status (P=0.003), time from stroke onset to rehabilitation admission (P<0.001), National Institutes of Health Stroke Scale score at rehabilitation admission (P<0.001), and aphasia (P=0.021) were independently associated with FIM gain. The R2 of the model was 0.275. During a median follow-up of 6.17 years, 36.9% of the patients died. At multivariable Cox analysis, age (P<0.0001), coronary heart disease (P=0.018), atrial fibrillation (P=0.042), total cholesterol (P=0.015), and total FIM gain (P<0.0001) were independently associated with mortality. The adjusted hazard ratio for death significantly decreased across tertiles of increasing FIM gain. Several factors are independently associated with functional gain after SR. Our findings strongly suggest that the magnitude of functional improvement is a powerful predictor of long-term mortality in patients admitted for SR. © 2015 American Heart Association, Inc.

Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma.

PubMed

Yeh, Hsin-Chih; Jan, Hau-Chern; Wu, Wen-Jeng; Li, Ching-Chia; Li, Wei-Ming; Ke, Hung-Lung; Huang, Shu-Pin; Liu, Chia-Chu; Lee, Yung-Chin; Yang, Sheau-Fang; Liang, Peir-In; Huang, Chun-Nung

2015-01-01

To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma. In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated. Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P < 0.001 and P = 0.001, respectively) than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis. Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract urothelial carcinoma.

A simple prognostic model for overall survival in metastatic renal cell carcinoma.

PubMed

Assi, Hazem I; Patenaude, Francois; Toumishey, Ethan; Ross, Laura; Abdelsalam, Mahmoud; Reiman, Tony

2016-01-01

The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis.

A simple prognostic model for overall survival in metastatic renal cell carcinoma

PubMed Central

Assi, Hazem I.; Patenaude, Francois; Toumishey, Ethan; Ross, Laura; Abdelsalam, Mahmoud; Reiman, Tony

2016-01-01

Introduction: The primary purpose of this study was to develop a simpler prognostic model to predict overall survival for patients treated for metastatic renal cell carcinoma (mRCC) by examining variables shown in the literature to be associated with survival. Methods: We conducted a retrospective analysis of patients treated for mRCC at two Canadian centres. All patients who started first-line treatment were included in the analysis. A multivariate Cox proportional hazards regression model was constructed using a stepwise procedure. Patients were assigned to risk groups depending on how many of the three risk factors from the final multivariate model they had. Results: There were three risk factors in the final multivariate model: hemoglobin, prior nephrectomy, and time from diagnosis to treatment. Patients in the high-risk group (two or three risk factors) had a median survival of 5.9 months, while those in the intermediate-risk group (one risk factor) had a median survival of 16.2 months, and those in the low-risk group (no risk factors) had a median survival of 50.6 months. Conclusions: In multivariate analysis, shorter survival times were associated with hemoglobin below the lower limit of normal, absence of prior nephrectomy, and initiation of treatment within one year of diagnosis. PMID:27217858

Reporting and methodological quality of survival analysis in articles published in Chinese oncology journals

PubMed Central

Zhu, Xiaoyan; Zhou, Xiaobin; Zhang, Yuan; Sun, Xiao; Liu, Haihua; Zhang, Yingying

2017-01-01

Abstract Survival analysis methods have gained widespread use in the filed of oncology. For achievement of reliable results, the methodological process and report quality is crucial. This review provides the first examination of methodological characteristics and reporting quality of survival analysis in articles published in leading Chinese oncology journals. To examine methodological and reporting quality of survival analysis, to identify some common deficiencies, to desirable precautions in the analysis, and relate advice for authors, readers, and editors. A total of 242 survival analysis articles were included to be evaluated from 1492 articles published in 4 leading Chinese oncology journals in 2013. Articles were evaluated according to 16 established items for proper use and reporting of survival analysis. The application rates of Kaplan–Meier, life table, log-rank test, Breslow test, and Cox proportional hazards model (Cox model) were 91.74%, 3.72%, 78.51%, 0.41%, and 46.28%, respectively, no article used the parametric method for survival analysis. Multivariate Cox model was conducted in 112 articles (46.28%). Follow-up rates were mentioned in 155 articles (64.05%), of which 4 articles were under 80% and the lowest was 75.25%, 55 articles were100%. The report rates of all types of survival endpoint were lower than 10%. Eleven of 100 articles which reported a loss to follow-up had stated how to treat it in the analysis. One hundred thirty articles (53.72%) did not perform multivariate analysis. One hundred thirty-nine articles (57.44%) did not define the survival time. Violations and omissions of methodological guidelines included no mention of pertinent checks for proportional hazard assumption; no report of testing for interactions and collinearity between independent variables; no report of calculation method of sample size. Thirty-six articles (32.74%) reported the methods of independent variable selection. The above defects could make potentially inaccurate, misleading of the reported results, or difficult to interpret. There are gaps in the conduct and reporting of survival analysis in studies published in Chinese oncology journals, severe deficiencies were noted. More endorsement by journals of the report guideline for survival analysis may improve articles quality, and the dissemination of reliable evidence to oncology clinicians. We recommend authors, readers, reviewers, and editors to consider survival analysis more carefully and cooperate more closely with statisticians and epidemiologists. PMID:29390340

Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.

PubMed

Zhao, Lu; Wang, Ruihao; Song, Bo; Tan, Song; Gao, Yuan; Fang, Hui; Lu, Jie; Xu, Yuming

2015-07-01

The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship. © 2015 World Stroke Organization.

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy.

PubMed

Langsenlehner, Tanja; Pichler, Martin; Thurner, Eva-Maria; Krenn-Pilko, Sabine; Stojakovic, Tatjana; Gerger, Armin; Langsenlehner, Uwe

2015-05-01

Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study. Data from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease-free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates. Using receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease-free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06-4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19-13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02-3.42, P = 0.044). Our findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them. Copyright © 2015 Elsevier Inc. All rights reserved.

Bio-psychosocial determinants of time lost from work following non life threatening acute orthopaedic trauma

PubMed Central

2010-01-01

Background To determine factors predicting the duration of time away from work following acute orthopaedic non life threatening trauma Methods Prospective cohort study conducted at four hospitals in Victoria, Australia. The cohort comprised 168 patients aged 18-64 years who were working prior to the injury and sustained a range of acute unintentional orthopaedic injuries resulting in hospitalization. Baseline data was obtained by survey and medical record review. Multivariate Cox proportional hazards regression analysis was used to examine the association between potential predictors and the duration of time away from work during the six month study. The study achieved 89% follow-up. Results Of the 168 participants recruited to the study, 68% returned to work during the six month study. Multivariate Cox proportional hazards regression analysis identified that blue collar work, negative pain attitudes with respect to work, high initial pain intensity, injury severity, older age, initial need for surgery, the presence of co-morbid health conditions at study entry and an orthopaedic injury to more than one region were associated with extended duration away from work following the injury. Participants in receipt of compensation who reported high social functioning at two weeks were 2.58 times more likely to have returned to work than similar participants reporting low social functioning. When only those who had returned to work were considered, the participant reported reason for return to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41 (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to" did not achieve significance. Conclusions Many injury-related and psycho social factors affect the duration of time away from work following orthopaedic injury. Some of these are potentially modifiable and may be amenable to intervention. Further consideration of the reasons provided by participants for returning to work may provide important opportunities for social marketing approaches designed to alleviate the financial and social burden associated with work disability. PMID:20051124

Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.

PubMed

Takahashi, Jun; Nihei, Taro; Takagi, Yusuke; Miyata, Satoshi; Odaka, Yuji; Tsunoda, Ryusuke; Seki, Atsushi; Sumiyoshi, Tetsuya; Matsui, Motoyuki; Goto, Toshikazu; Tanabe, Yasuhiko; Sueda, Shozo; Momomura, Shin-ichi; Yasuda, Satoshi; Ogawa, Hisao; Shimokawa, Hiroaki

2015-01-21

Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered. Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?

PubMed

Ibrahim, Fowzia; Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-11-01

RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients.

PubMed

Cai, Kedan; Luo, Qun; Dai, Zhiwei; Zhu, Beixia; Fei, Jinping; Xue, Congping; Wu, Dan

2016-01-01

Hypomagnesemia has been associated with an increase in mortality among the general population as well as patients with chronic kidney disease or those on hemodialysis. However, this association has not been thoroughly studied in patients undergoing peritoneal dialysis. The aim of this study was to evaluate the association between serum magnesium concentrations and all-cause and cardiovascular mortalities in peritoneal dialysis patients. This single-center retrospective study included 253 incident peritoneal dialysis patients enrolled between July 1, 2005 and December 31, 2014 and followed to June 30, 2015. Patient's demographic characteristics as well as clinical and laboratory measurements were collected. Of 253 patients evaluated, 36 patients (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months (range: 4-120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths were attributed to cardiovascular causes. Low serum magnesium was positively associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160, p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a lower survival rate than those in the normal magnesium groups (p < 0.001). In a multivariate Cox proportional hazards regression analysis, serum magnesium was an independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075, p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in female patients. However, in univariate and multivariate Cox analysis, △Mg(difference between 1-year magnesium and baseline magnesium) was not an independent predictor of all-cause mortality and cardiovascular mortality. Hypomagnesemia was common among peritoneal dialysis patients and was independently associated with all-cause mortality and cardiovascular mortality.

Squamous cell carcinoma of the breast in the United States: incidence, demographics, tumor characteristics, and survival.

PubMed

Yadav, Siddhartha; Yadav, Dhiraj; Zakalik, Dana

2017-07-01

Squamous cell carcinoma of breast accounts for less than 0.1% of all breast cancers. The purpose of this study is to describe the epidemiology and survival of this rare malignancy. Data were extracted from the National Cancer Institute's Surveillance, Epidemiology and End Results Registry to identify women diagnosed with squamous cell carcinoma of breast between 1998 and 2013. SEER*Stat 8.3.1 was used to calculate age-adjusted incidence, age-wise distribution, and annual percentage change in incidence. Kaplan-Meier curves were plotted for survival analysis. Univariate and multivariate Cox proportional hazard regression model was used to determine predictors of survival. A total of 445 cases of squamous cell carcinoma of breast were diagnosed during the study period. The median age of diagnosis was 67 years. The overall age-adjusted incidence between 1998 and 2013 was 0.62 per 1,000,000 per year, and the incidence has been on a decline. Approximately half of the tumors were poorly differentiated. Stage II was the most common stage at presentation. Majority of the cases were negative for expression of estrogen and progesterone receptor. One-third of the cases underwent breast conservation surgery while more than half of the cases underwent mastectomy (unilateral or bilateral). Approximately one-third of cases received radiation treatment. The 1-year and 5-year cause-specific survival was 81.6 and 63.5%, respectively. Excluding patient with metastasis or unknown stage at presentation, in multivariate Cox proportional hazard model, older age at diagnosis and higher tumor stage (T3 or T4) or nodal stage at presentation were significant predictors of poor survival. Our study describes the unique characteristics of squamous cell carcinoma of breast and demonstrates that it is an aggressive tumor with a poor survival. Older age and higher tumor or nodal stages at presentation were independent predictors of poor survival for loco-regional stages.

Bio-psychosocial determinants of time lost from work following non life threatening acute orthopaedic trauma.

PubMed

Clay, Fiona J; Newstead, Stuart V; Watson, Wendy L; Ozanne-Smith, Joan; McClure, Roderick J

2010-01-05

To determine factors predicting the duration of time away from work following acute orthopaedic non life threatening trauma Prospective cohort study conducted at four hospitals in Victoria, Australia. The cohort comprised 168 patients aged 18-64 years who were working prior to the injury and sustained a range of acute unintentional orthopaedic injuries resulting in hospitalization. Baseline data was obtained by survey and medical record review. Multivariate Cox proportional hazards regression analysis was used to examine the association between potential predictors and the duration of time away from work during the six month study. The study achieved 89% follow-up. Of the 168 participants recruited to the study, 68% returned to work during the six month study. Multivariate Cox proportional hazards regression analysis identified that blue collar work, negative pain attitudes with respect to work, high initial pain intensity, injury severity, older age, initial need for surgery, the presence of co-morbid health conditions at study entry and an orthopaedic injury to more than one region were associated with extended duration away from work following the injury. Participants in receipt of compensation who reported high social functioning at two weeks were 2.58 times more likely to have returned to work than similar participants reporting low social functioning. When only those who had returned to work were considered, the participant reported reason for return to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41 (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to" did not achieve significance. Many injury-related and psycho social factors affect the duration of time away from work following orthopaedic injury. Some of these are potentially modifiable and may be amenable to intervention. Further consideration of the reasons provided by participants for returning to work may provide important opportunities for social marketing approaches designed to alleviate the financial and social burden associated with work disability.

Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Showalter, Timothy N., E-mail: tns3b@virginia.edu; Hegarty, Sarah E.; Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania

Purpose: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. Methods: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapymore » were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. Results: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). Conclusion: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events. However, the timing of radiation therapy did not influence the risk of radiation therapy–associated adverse events in this cohort, which contradicts the commonly held clinical tenet that delaying radiation therapy reduces the risk of adverse events.« less

Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tucker, Susan L., E-mail: sltucker@mdanderson.org; Dong, Lei; Michalski, Jeff M.

2012-10-01

Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportionmore » of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.« less

Job stress and mortality in older age.

PubMed

Tobiasz-Adamczyk, Beata; Brzyski, Piotr; Florek, Marzena; Brzyska, Monika

2013-06-01

This paper aims to assess the relationship between the determinants of the psychosocial work environment, as expressed in terms of JDC or ERI models, and all-cause mortality in older individuals. The baseline study was conducted on a cohort comprising a random sample of 65-year-old community-dwelling citizens of Kraków, Poland. All of the 727 participants (410 women, 317 men) were interviewed in their households in the period between 2001 and 2003; a structured questionnaire was used regarding their occupational activity history, which included indexes measuring particular dimensions of their psychosocial work environment based on Karasek's Job Demand-Control model and Siegrist's Effort-Reward Imbalance model, as well as health-related quality of life and demographic data. Mortality was ascertained by monitoring City Vital Records for 7 years. Analyses were conducted separately for men and women, with the multivariate Cox proportional hazard model. During a 7-year follow-up period, 59 participants (8.1%) died, including 21 women (5.1% of total women) and 38 men (12%) (p < 0.05). Significant differences in the number of deaths occurred regarding disproportion between physical demands and control in men: those with low physical demands and low control died three times more often than those with high control, regardless of the level of demands. The multivariate Cox proportional hazard model showed that significantly higher risk of death was observed only in men with low physical demands and low control, compared to those with low physical demands and high control (Exp(B) = 4.65, 95% CI: 1.64-13.2). Observed differences in mortality patterns are similar to the patterns of relationships observed in health-related quality of life (HRQoL) level at the beginning of old age; however, the relationship between efforts and rewards or demands and control and mortality was not fully confirmed.

Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, T. Jonathan; Oh, Jung Hun; Folkert, Michael R.

2014-11-01

Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system wasmore » used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.« less

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients: A retrospective study.

PubMed

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-12-01

Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients' technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients.This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes.During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality.We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality.These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes.

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients

PubMed Central

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-01-01

Abstract Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients’ technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients. This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes. During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality. We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality. These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes. PMID:27930566

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma.

PubMed

Jia, Shou-Wei; Fu, Sha; Wang, Fang; Shao, Qiong; Huang, Hong-Bing; Shao, Jian-Yong

2014-01-07

To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients. A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ(2) test or Fisher's exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model. ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046). ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor.

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma

PubMed Central

Jia, Shou-Wei; Fu, Sha; Wang, Fang; Shao, Qiong; Huang, Hong-Bing; Shao, Jian-Yong

2014-01-01

AIM: To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients. METHODS: A total of 213 cases of HCC were examined by fluorescent in situ hybridization using dual color break-apart ALK probes for the detection of chromosomal translocation and gene copy number gain. HCC tissue microarrays were constructed, and the correlation between the ALK status and clinicopathological variables was assessed by χ2 test or Fisher’s exact test. Survival analysis was estimated using the Kaplan-Meier approach with a Log-rank test. Univariate and multivariate analyses of clinical variables were performed using the Cox proportional hazards regression model. RESULTS: ALK gene translocation was not observed in any of the HCC cases included in the present study. ALK gene copy number gain (ALK/CNG) (≥ 4 copies/cell) was detected in 28 (13.15%) of the 213 HCC patients. The 3-year progression-free-survival (PFS) rate for ALK/CNG-positive HCC patients was significantly poorer than ALK/CNG-negative patients (27.3% vs 42.5%, P = 0.048), especially for patients with advanced stage III/IV (0% vs 33.5%, P = 0.007), and patients with grade III disease (24.8% vs 49.9%, P = 0.023). ALK/CNG-positive HCC patients had a significantly poorer prognosis than ALK/CNG-negative patients in the subgroup that was negative for serum hepatitis B virus DNA, with significantly different 3-year overall survival rates (18.2% vs 63.6%, P = 0.021) and PFS rates (18.2% vs 46.9%, P = 0.019). Multivariate Cox proportional hazards regression analysis suggested that ALK/CNG prevalence can predict death in HCC (HR = 1.596; 95%CI: 1.008-2.526, P = 0.046). CONCLUSION: ALK/CNG, but not translocation of ALK, is present in HCC and may be an unfavorable prognostic predictor. PMID:24415871

Forkhead-box series expression network is associated with outcome of clear-cell renal cell carcinoma.

PubMed

Jia, Zhongwei; Wan, Fangning; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Dai, Bo; Ye, Dingwei

2018-06-01

Previous studies have demonstrated that several members of the Forkhead-box (FOX) family of genes are associated with tumor progression and metastasis. The objective of the current study was to screen candidate FOX family genes identified from analysis of molecular networks in clear cell renal cell carcinoma (ccRCC). The expression of FOX family genes as well as FOX family-associated genes was examined, and Kaplan-Meier survival analysis was performed in The Cancer Genome Atlas (TCGA) cohort (n=525). Patient characteristics, including sex, age, tumor diameter, laterality, tumor-node-metastasis, tumor grade, stage, white blood cell count, platelet count, the levels of hemoglobin, overall survival (OS) and disease-free survival (DFS), were collected for univariate and multivariate Cox proportional hazards ratio analyses. A total of seven candidate FOX family genes were selected from the TCGA database subsequent to univariate and multivariate Cox proportional hazards ratio analyses. FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 were associated with poor OS time, while FOXA1, FOXA2, FOXD1 and FOXK2 were associated with poor DFS time (P<0.05). FOXN2 was associated with favorable outcomes for overall and disease-free survival (P<0.05). In the gene cluster network analysis, the expression of FOX family-associated genes, including nuclear receptor coactivator ( NCOA ) 1 , NADH-ubiquinone oxidoreductase flavoprotein 3 ( NDUFV3 ), phosphatidylserine decarboxylase ( PISD ) and pyruvate kinase liver and red blood cell ( PKLR ), were independent prognostic factors for OS in patients with ccRCC. Results of the present study revealed that the expression of FOX family genes, including FOXA1, FOXA2, FOXD1, FOXD4L2, FOXK2 and FOXL1 , and FOX family-associated genes, including NCOA1, NDUFV3, PISD and PKLR , are independent prognostic factors for patients with ccRCC.

Utilization of Body Contouring Procedures Following Weight Loss Surgery: A Study of 37,806 Patients.

PubMed

Altieri, Maria S; Yang, Jie; Park, Jihye; Novikov, David; Kang, Lijuan; Spaniolas, Konstantinos; Bates, Andrew; Talamini, Mark; Pryor, Aurora

2017-11-01

Bariatric surgery has substantial health benefits; however, some patients desire body contouring (BC) procedures following rapid weight loss. There is a paucity of data regarding the true rate of BC following bariatric procedures. The purpose of our study is to examine the utilization of two common procedures, abdominoplasty, and panniculectomy, following bariatric surgery in New York State. The SPARCS longitudinal administrative database was used to identify bariatric procedures by using ICD-9 and CPT codes between 2004 and 2010. Procedures included sleeve gastrectomy, Roux-en-Y gastric bypass, and laparoscopic adjustable gastric banding. Using a unique patient identifier, we tracked those patients who subsequently underwent either abdominoplasty or panniculectomy with at least a 4-year follow-up (until 2014). Multivariable Cox proportional hazard model was used to evaluate predictors of follow-up BC surgery. 37,806 patients underwent bariatric surgery between 2004 and 2010. Only 5.58% (n = 2112) of these patients subsequently had a BC procedure, with 143 of them (6.8%) having ≥1 plastic surgery. The average time to plastic surgery after band, bypass, or sleeve was 1134.83 ± 671.09, 984.70 ± 570.53, and 903.02 ± 497.31 days, respectively (P < 0.0001). Following the multivariable Cox proportional hazard model, a female, SG patients, patients with Medicare or Medicaid, and patients in either <20 or >80%ile in yearly income were more likely to have plastic surgery after adjusting for age, race/ethnicity, comorbidities and complications (P values < 0.0001). This study shows that plastic surgery is completed by only 6% of patients following bariatric procedures. As insurance and income are associated with pursuing surgery, improved access may increase the number of patients who are able to undergo these reconstructive procedures.

Effect of hyperlipidemia on the incidence of cardio-cerebrovascular events in patients with type 2 diabetes.

PubMed

Fan, Dabei; Li, Li; Li, Zhizhen; Zhang, Ying; Ma, Xiaojun; Wu, Lina; Qin, Guijun

2018-05-08

This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox's proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). At the end of the follow-up period, all-cause mortality, cardio-cerebrovascular diseases mortality, and the incidence of myocardial infarction, cerebral infarction, cerebral hemorrhage and total cardiovascular events were significantly higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). The analysis results of multivariable Cox's proportional hazards regression model showed that the risks of myocardial infarction and total cardiovascular events in diabetes combined with hyperlipidemia group were respectively 1.54 times (95%CI 1.13-2.07) and 1.68 times (95%CI 1.23-2.24) higher than those in diabetes group. Population attributable risk percent of all-cause mortality and total cardiovascular events in patients with type 2 diabetes combined with hyperlipidemia was 9.6% and 26.8%, respectively. Hyperlipidemia may promote vascular endothelial injury, increasing the risk of cardio-cerebrovascular diseases in patients with type 2 diabetes. Medical staffs should pay attention to the control of blood lipids in patients with type 2 diabetes to delay the occurrence of cardio-cerebrovascular diseases.

Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients

PubMed Central

Dai, Zhiwei; Zhu, Beixia; Fei, Jinping; Xue, Congping; Wu, Dan

2016-01-01

Objective Hypomagnesemia has been associated with an increase in mortality among the general population as well as patients with chronic kidney disease or those on hemodialysis. However, this association has not been thoroughly studied in patients undergoing peritoneal dialysis. The aim of this study was to evaluate the association between serum magnesium concentrations and all-cause and cardiovascular mortalities in peritoneal dialysis patients. Methods This single-center retrospective study included 253 incident peritoneal dialysis patients enrolled between July 1, 2005 and December 31, 2014 and followed to June 30, 2015. Patient’s demographic characteristics as well as clinical and laboratory measurements were collected. Results Of 253 patients evaluated, 36 patients (14.2%) suffered from hypomagnesemia. During a median follow-up of 29 months (range: 4–120 months), 60 patients (23.7%) died, and 35 (58.3%) of these deaths were attributed to cardiovascular causes. Low serum magnesium was positively associated with peritoneal dialysis duration (r = 0.303, p < 0.001) as well as serum concentrations of albumin (r = 0.220, p < 0.001), triglycerides (r = 0.160, p = 0.011), potassium (r = 0.156, p = 0.013), calcium(r = 0.299, p < 0.001)and phosphate (r = 0.191, p = 0.002). Patients in the hypomagnesemia group had a lower survival rate than those in the normal magnesium groups (p < 0.001). In a multivariate Cox proportional hazards regression analysis, serum magnesium was an independent negative predictor of all-cause mortality (hazard ratio [HR] = 0.075, p = 0.011) and cardiovascular mortality (HR = 0.003, p < 0.001), especially in female patients. However, in univariate and multivariate Cox analysis, △Mg(difference between 1-year magnesium and baseline magnesium) was not an independent predictor of all-cause mortality and cardiovascular mortality. Conclusion Hypomagnesemia was common among peritoneal dialysis patients and was independently associated with all-cause mortality and cardiovascular mortality. PMID:27023783

Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

PubMed Central

Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

2017-01-01

Abstract Objectives RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. Methods We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0–6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6–12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Results Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0–6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6–12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Conclusion Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. Trail registration EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701 PMID:28968858

Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

PubMed

Bang, Casper N; Greve, Anders M; La Cour, Morten; Boman, Kurt; Gohlke-Bärwolf, Christa; Ray, Simon; Pedersen, Terje; Rossebø, Anne; Okin, Peter M; Devereux, Richard B; Wachtell, Kristian

2015-12-15

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Predictors of in-hospital mortality amongst octogenarians undergoing emergency general surgery: a retrospective cohort study.

PubMed

Wilson, Iain; Paul Barrett, Michael; Sinha, Ashish; Chan, Shirley

2014-11-01

Elderly patients are often judged to be fit for emergency surgery based on age alone. This study identified risk factors predictive of in-hospital mortality amongst octogenarians undergoing emergency general surgery. A retrospective review of octogenarians undergoing emergency general surgery over 3 years was performed. Parametric survival analysis using Cox multivariate regression model was used to identify risk factors predictive of in-hospital mortality. Hazard ratios (HR) and corresponding 95% confidence interval were calculated. Seventy-three patients with a median age of 84 years were identified. Twenty-eight (38%) patients died post-operatively. Multivariate analysis identified ASA grade (ASA 5 HR 23.4 95% CI 2.38-230, p = 0.007) and chronic obstructive pulmonary disease (COPD) (HR 3.35 95% CI 1.15-9.69, p = 0.026) to be the only significant predictors of in-hospital mortality. Identification of high risk surgical patients should be based on physiological fitness for surgery rather than chronological age. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Myocardial Injury in Patients With Sepsis and Its Association With Long-Term Outcome.

PubMed

Frencken, Jos F; Donker, Dirk W; Spitoni, Cristian; Koster-Brouwer, Marlies E; Soliman, Ivo W; Ong, David S Y; Horn, Janneke; van der Poll, Tom; van Klei, Wilton A; Bonten, Marc J M; Cremer, Olaf L

2018-02-01

Sepsis is frequently complicated by the release of cardiac troponin, but the clinical significance of this myocardial injury remains unclear. We studied the associations between troponin release during sepsis and 1-year outcomes. We enrolled consecutive patients with sepsis in 2 Dutch intensive care units between 2011 and 2013. Subjects with a clinically apparent cause of troponin release were excluded. High-sensitivity cardiac troponin I (hs-cTnI) concentration in plasma was measured daily during the first 4 intensive care unit days, and multivariable Cox regression analysis was used to model its association with 1-year mortality while adjusting for confounding. In addition, we studied cardiovascular morbidity occurring during the first year after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%) were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673 (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4 days. Cox regression analysis revealed that high hs-cTnI concentrations were associated with increased death rates during the first 14 days (adjusted hazard ratio, 1.72; 95% confidence interval, 1.14-2.59 and hazard ratio, 1.70; 95% confidence interval, 1.10-2.62 for hs-cTnI concentrations of 100-500 and >500 ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were associated with the development of cardiovascular disease among 200 hospital survivors who were analyzed for this end point (adjusted subdistribution hazard ratio, 1.25; 95% confidence interval, 1.04-1.50). Myocardial injury occurs in the majority of patients with sepsis and is independently associated with early-but not late-mortality, as well as postdischarge cardiovascular morbidity. © 2018 American Heart Association, Inc.

Cardiac sympathetic denervation and dementia in de novo Parkinson's disease: A 7-year follow-up study.

PubMed

Choi, Mun Hee; Yoon, Jung Han; Yong, Suk Woo

2017-10-15

Postganglionic cardiac sympathetic denervation is evident in patients with early-stage Parkinson's disease (PD). Cardiac iodine-123-meta-iodobenzylguanidine (MIBG) uptake is correlated with the non-motor symptoms of PD, suggesting that low cardiac MIBG uptake may reflect wider alpha-synuclein pathology. In addition, low cardiac MIBG could be related to orthostatic hypotension in PD, which may affect cognition. However, the prognostic validity of baseline MIBG scintigraphy in terms of the risk of subsequent dementia remains unclear. We investigated whether cardiac MIBG uptake was associated with a later risk of dementia. We retrospectively enrolled 93 drug-naive patients with de novo PD who underwent MIBG scanning on initial evaluation. The patients visited our outpatient clinic every 3-6months and were followed-up for a minimum of 4years from the time they were begun on dopaminergic medication. The predictive powers of baseline MIBG cardiac scintigraphic data in terms of dementia development were evaluated using Cox's proportional hazard models. During a mean follow-up period of 6.7years, 27 patients with PD (29.0%) developed dementia. These patients had less baseline MIBG uptake than did others (delayed H/M ratios: 1.19 vs. 1.31). Multivariate Cox's proportional hazard modeling revealed that both MIBG uptake (hazard ratio [HR] 3.40; p=0.004) and age (HR 1.08, p=0.01) significantly predicted dementia development. A reduction in cardiac MIBG uptake by PD patients may be associated with a subsequent risk of dementia; reduced uptake may reflect wider extension of alpha-synuclein pathology in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

PubMed

Afarideh, Mohsen; Aryan, Zahra; Ghajar, Alireza; Noshad, Sina; Nakhjavani, Manouchehr; Baber, Usman; Mechanick, Jeffrey I; Esteghamati, Alireza

2016-11-01

We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], p for trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Age at introduction of ultra-processed food among preschool children attending day-care centers.

PubMed

Longo-Silva, Giovana; Silveira, Jonas Augusto C; Menezes, Rísia Cristina Egito de; Toloni, Maysa Helena de Aguiar

To identify the age of introduction of ultra-processed food and its associated factors among preschool children. Cross-sectional study carried out from March to June 2014 with 359 preschool children aged 17 to 63 months attending day-care centers. Time until ultra-processed food introduction (outcome variable) was described by the Kaplan-Meier analysis, and the log-rank test was used to compare the survival functions of independent variables. Factors associated with ultra-processed food introduction were investigated using the multivariate Cox proportional hazards model. The results were shown as hazard ratios with their respective 95% confidence intervals. The median time until ultra-processed food introduction was six months. Between the 3rd and 6th months, there is a significant increase in the probability of introducing ultra-processed food in the children's diet; and while the probability in the 3rd month varies from 0.15 to 0.25, at six months the variation ranges from 0.6 to 1.0. The final Cox proportional hazards model showed that unplanned pregnancy (1.32 [1.05-1.65]), absence of prenatal care (2.50 [1.02-6.16]), and income >2 minimum wages (1, 50 [1.09-2.06]) were independent risk factors for the introduction of ultra-processed food. Up to the 6th month of life, approximately 75% of preschool children had received one or more ultra-processed food in their diet. In addition, it was observed that the poorest families, as well as unfavorable prenatal factors, were associated with early introduction of ultra-processed food. Copyright © 2017. Published by Elsevier Editora Ltda.

Increased pulse wave velocity in patients with acute lacunar infarction doubled the risk of future ischemic stroke.

PubMed

Saji, Naoki; Murotani, Kenta; Shimizu, Hirotaka; Uehara, Toshiyuki; Kita, Yasushi; Toba, Kenji; Sakurai, Takashi

2017-04-01

The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

Glyburide increases risk in patients with diabetes mellitus after emergent percutaneous intervention for myocardial infarction--a nationwide study.

PubMed

Jørgensen, C H; Gislason, G H; Bretler, D; Sørensen, R; Norgaard, M L; Hansen, M L; Schramm, T K; Abildstrom, S Z; Torp-Pedersen, C; Hansen, P R

2011-11-03

Sulfonylureas have been linked to an increased cardiovascular risk by inhibition of myocardial preconditioning. Whether individual sulfonylureas affect outcomes in diabetic patients after emergent percutaneous coronary intervention for myocardial infarction is unknown. All Danish patients receiving glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006 who underwent emergent percutaneous coronary intervention were identified from national registers. Multivariable Cox proportional hazards models were used to analyze the risk of cardiovascular mortality and morbidity associated with sulfonylureas. A total of 926 patients were included and 163 (17.6%) patients died during the first year of which 155 (16.7%) were cardiovascular deaths. The most common treatment was sulfonylureas which were received by 271 (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard regression analyses adjusted for age, sex, calendar year, comorbidity and concomitant pharmacotherapy showed an increased risk of cardiovascular mortality (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p=0.012), cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI 1.21-6.00; p=0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47; p=0.027), respectively, with glyburide compared to metformin. Glyburide is associated with increased cardiovascular mortality and morbidity in patients with diabetes mellitus undergoing emergent percutaneous coronary intervention after myocardial infarction. Early reperfusion therapy is the mainstay in modern treatment of myocardial infarction and the time may have come to discard glyburide in favour of sulfonylureas that do not appear to confer increased cardiovascular risk. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Untangling the Relationship Between Antiretroviral Therapy Use and Incident Pregnancy: A Marginal Structural Model Analysis Using Data From 47,313 HIV-Positive Women in East Africa.

PubMed

Elul, Batya; Wools-Kaloustian, Kara K; Wu, Yingfeng; Musick, Beverly S; Nuwagaba-Biribonwoha, Harriet; Nash, Denis; Ayaya, Samuel; Bukusi, Elizabeth; Okong, Pius; Otieno, Juliana; Wabwire, Deo; Kambugu, Andrew; Yiannoutsos, Constantin T

2016-07-01

Scale-up of triple-drug antiretroviral therapy (ART) in Africa has transformed the context of childbearing for HIV-positive women and may impact pregnancy incidence in HIV programs. Using observational data from 47,313 HIV-positive women enrolled at 26 HIV clinics in Kenya and Uganda between 2001 and 2009, we calculated the crude cumulative incidence of pregnancy for the pre-ART and on-ART periods. The causal effect of ART use on incident pregnancy was assessed using inverse probability weighted marginal structural models, and the relationship was further explored in multivariable Cox models. Crude cumulative pregnancy incidence at 1 year after enrollment/ART initiation was 4.0% and 3.9% during the pre-ART and on-ART periods, respectively. In marginal structural models, ART use was not significantly associated with incident pregnancy [hazard ratio = 1.06; 95% confidence interval (CI): 0.99 to 1.12]. Similarly, in Cox models, there was no significant relationship between ART use and incident pregnancy (cause-specific hazard ratio: 0.98; 95% CI: 0.91 to 1.05), but effect modification was observed. Specifically, women who were pregnant at enrollment and on ART had an increased risk of incident pregnancy compared to those not pregnant at enrollment and not on ART (cause-specific hazard ratio: 1.11; 95% CI: 1.01 to 1.23). In this large cohort, ART initiation was not associated with incident pregnancy in the general population of women enrolling in HIV care but rather only among those pregnant at enrollment. This finding further highlights the importance of scaling up access to lifelong treatment for pregnant women.

Untangling the Relationship Between Antiretroviral Therapy Use and Incident Pregnancy: A Marginal Structural Model Analysis Using Data From 47,313 HIV-Positive Women in East Africa

PubMed Central

Wools-Kaloustian, Kara K.; Wu, Yingfeng; Musick, Beverly S.; Nuwagaba-Biribonwoha, Harriet; Nash, Denis; Ayaya, Samuel; Bukusi, Elizabeth; Okong, Pius; Otieno, Juliana; Wabwire, Deo; Kambugu, Andrew; Yiannoutsos, Constantin T.

2016-01-01

Background: Scale-up of triple-drug antiretroviral therapy (ART) in Africa has transformed the context of childbearing for HIV-positive women and may impact pregnancy incidence in HIV programs. Methods: Using observational data from 47,313 HIV-positive women enrolled at 26 HIV clinics in Kenya and Uganda between 2001 and 2009, we calculated the crude cumulative incidence of pregnancy for the pre-ART and on-ART periods. The causal effect of ART use on incident pregnancy was assessed using inverse probability weighted marginal structural models, and the relationship was further explored in multivariable Cox models. Results: Crude cumulative pregnancy incidence at 1 year after enrollment/ART initiation was 4.0% and 3.9% during the pre-ART and on-ART periods, respectively. In marginal structural models, ART use was not significantly associated with incident pregnancy [hazard ratio = 1.06; 95% confidence interval (CI): 0.99 to 1.12]. Similarly, in Cox models, there was no significant relationship between ART use and incident pregnancy (cause-specific hazard ratio: 0.98; 95% CI: 0.91 to 1.05), but effect modification was observed. Specifically, women who were pregnant at enrollment and on ART had an increased risk of incident pregnancy compared to those not pregnant at enrollment and not on ART (cause-specific hazard ratio: 1.11; 95% CI: 1.01 to 1.23). Conclusions: In this large cohort, ART initiation was not associated with incident pregnancy in the general population of women enrolling in HIV care but rather only among those pregnant at enrollment. This finding further highlights the importance of scaling up access to lifelong treatment for pregnant women. PMID:26910499

Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy.

PubMed

Xiao, Yan; Yang, Kun-Qi; Yang, Yan-Kun; Liu, Ya-Xin; Tian, Tao; Song, Lei; Jiang, Xiong-Jing; Zhou, Xian-Liang

2015-06-05

End-stage hypertrophic cardiomyopathy (HCM) is complicated by substantial adverse events. However, few studies have focused on electrocardiographic features and their prognostic values in HCM. This study aimed to evaluate the clinical manifestations and prognostic value of electrocardiography in patients with end-stage HCM. End-stage HCM patients were enrolled from a total of 1844 consecutive HCM patients from April 2002 to November 2013 at Fuwai Hospital. Clinical data, including medical history, electrocardiography, and echocardiography, were analyzed. Cox hazards regression analysis was used to assess the risk factors for cardiovascular mortality. End-stage HCM was identified in 99 (5.4%) patients, averaged at 52 ± 16 years old at entry. Atrial fibrillation was observed in 53 patients and mural thrombus in 19 patients. During 3.9 ± 3.0 years of follow-up, embolic stroke, refractory heart failure, and death or transplantation were observed in 20, 39, and 51 patients, respectively. The incidence of annual mortality was 13.2%. Multivariate Cox hazards regression analysis identified New York Heart Association Class (NYHA) III/IV at entry (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.05-3.80; P = 0.036), left bundle branch block (LBBB) (HR: 2.80; 95% CI: 1.47-5.31; P = 0.002), and an abnormal Q wave (HR: 2.21; 95% CI: 1.16-4.23; P = 0.016) as independent predictors of cardiovascular death, in accordance with all-cause death and heart failure-related death. LBBB and an abnormal Q wave are risk factors of cardiovascular mortality in end-stage HCM and provide new evidence for early intervention. Susceptibility of end-stage HCM patients to mural thrombus and embolic events warrants further attention.

Incidence of silicosis among ceramic workers in central Italy.

PubMed

Cavariani, F; Di Pietro, A; Miceli, M; Forastiere, F; Biggeri, A; Scavalli, P; Petti, A; Borgia, P

1995-01-01

The incidence of radiological silicosis was studied among 2480 male workers employed in the ceramics industry. The subjects entered the surveillance program during 1974-1987 and were followed through 1991 with annual chest radiographs. The cumulative risk of silicosis (1/1 or greater; p,q,r) reached 48% (95% confidence interval 41.5-54.9) after 30 years of employment. In a multivariate Cox's proportional hazards model, the effect of duration of exposure increased linearly up to the category of 25-29 years; an extremely high hazard risk of 14.6 was found among those with 30 years or more of exposure in comparison with those employed 10 years or less. Smoking habit also significantly contributed to the model, although its role in the biological process is unclear. In conclusion, exposure to silica dust has been associated with a high incidence of silicosis among ceramics workers. The risk estimates are consistent with the recent findings of silicosis incidence among South African gold miners.

Lifestyle and the risk of diabetes mellitus in a Japanese population.

PubMed

Tatsumi, Yukako; Ohno, Yuko; Morimoto, Akiko; Nishigaki, Yoshio; Mizuno, Shoichi; Watanabe, Shaw

2013-06-01

The objective was to examine the association between lifestyle and risk for diabetes. For an average of 9.9 years, this study prospectively followed a cohort of 7,211 (2,524 men and 4,687 women) community residents aged 30-69 years without diabetes at a health check-up conducted between April 1990 and March 1992 until diabetes was confirmed or until the end of 2006. The subjects were divided into 6 groups according to their total scores of Breslow's lifestyle index (1-2, 3, 4, 5, 6 and 7 points). The association between lifestyle and diabetes incidence was investigated using Cox proportional hazards regression models. The results showed that the multivariate-adjusted hazard ratios were 0.45 in subjects who scored 5 points, 0.39 in subjects who scored 6 points, and 0.31 in subjects who scored 7 points, compared with subjects who scored 1-2 points. These data indicate that the healthy behaviors prevent the incidence of diabetes.

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

PubMed

Tam, Samantha; Sandulache, Vlad C; Metwalli, Kareem A; Rock, Crosby D; Eraj, Salman A; Sheu, Tommy; El-Naggar, Adel K; Fuller, Clifton D; Weber, Randal S; Lai, Stephen Y

2018-05-07

Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HR adjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HR adjusted 9.53; 95% CI 3.04-27.06). Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival. © 2018 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

VanderWalde, Noam A.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Meyer, Anne Marie

Purpose: The purpose of this study was to compare chemoradiation therapy (CRT) with radiation therapy (RT) only in an older patient population with head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007), we identified a retrospective cohort of nonmetastatic HNSCC patients and divided them into treatment groups. Comparisons were made between CRT and RT cohorts. Propensity scores for CRT were estimated from covariates associated with receipt of treatment using multivariable logistic regression. Standardized mortality ratio weights (SMRW) were created from the propensity scores and used to balance groupsmore » on measured confounders. Multivariable and SMR-weighted Cox proportional hazard models were used to estimate the hazard ratio (HR) of death for receipt of CRT versus RT among the whole group and for separate patient and tumor categories. Results: The final cohort of 10,599 patients was 68% male and 89% white. Median age was 74 years. Seventy-four percent were treated with RT, 26% were treated with CRT. Median follow-up points for CRT and RT survivors were 4.6 and 6.3 years, respectively. On multivariable analysis, HR for death with CRT was 1.13 (95% confidence interval [CI]: 1.07-1.20; P<.01). Using the SMRW model, the HR for death with CRT was 1.08 (95% CI: 1.02-1.15; P=.01). Conclusions: Although the addition of chemotherapy to radiation has proven efficacious in many randomized controlled trials, it may be less effective in an older patient population treated outside of a controlled trial setting.« less

Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia.

PubMed

Hansson, Lotta; Asklid, Anna; Diels, Joris; Eketorp-Sylvan, Sandra; Repits, Johanna; Søltoft, Frans; Jäger, Ulrich; Österborg, Anders

2017-10-01

This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial. A multivariate Cox proportional hazards regression model was used which estimated the hazard ratio (HR) of ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus the previous standard-of-care cohort was 0.15 (p < 0.0001) for progression-free survival (PFS) and 0.36 (p < 0.0001) for overall survival (OS). A similar difference was observed also when patients treated late in the period (2012-) were compared separately. Multivariate analysis showed that later line of therapy, male gender, older age and poor performance status were significant independent risk factors for worse PFS and OS. Our results suggest that PFS and OS with ibrutinib in the RESONATE study were significantly longer than with previous standard-of-care regimens used in second or later lines in routine healthcare. The approach used, which must be interpreted with caution, compares patient-level data from a clinical trial with outcomes observed in a daily clinical practice and may complement results from randomised trials or provide preliminary wider comparative information until phase 3 data exist.

Association of educational attainment with chronic disease and mortality: the Kidney Early Evaluation Program (KEEP).

PubMed

Choi, Andy I; Weekley, Cristin C; Chen, Shu-Cheng; Li, Suying; Tamura, Manjula Kurella; Norris, Keith C; Shlipak, Michael G

2011-08-01

Recent reports have suggested a close relationship between education and health, including mortality, in the United States. Observational cohort. We studied 61,457 participants enrolled in a national health screening initiative, the National Kidney Foundation's Kidney Early Evaluation Program (KEEP). Self-reported educational attainment. Chronic diseases (hypertension, diabetes, cardiovascular disease, reduced kidney function, and albuminuria) and mortality. We evaluated cross-sectional associations between self-reported educational attainment with the chronic diseases listed using logistic regression models adjusted for demographics, access to care, behaviors, and comorbid conditions. The association of educational attainment with survival was determined using multivariable Cox proportional hazards regression. Higher educational attainment was associated with a lower prevalence of each of the chronic conditions listed. In multivariable models, compared with persons not completing high school, college graduates had a lower risk of each chronic condition, ranging from 11% lower odds of decreased kidney function to 37% lower odds of cardiovascular disease. During a mean follow-up of 3.9 (median, 3.7) years, 2,384 (4%) deaths occurred. In the fully adjusted Cox model, those who had completed college had 24% lower mortality compared with participants who had completed at least some high school. Lack of income data does not allow us to disentangle the independent effects of education from income. In this diverse contemporary cohort, higher educational attainment was associated independently with a lower prevalence of chronic diseases and short-term mortality in all age and race/ethnicity groups. Published by Elsevier Inc.

Survival in Alzheimer disease

PubMed Central

Helzner, E P.; Scarmeas, N; Cosentino, S; Tang, M X.; Schupf, N; Stern, Y

2008-01-01

Objective: To describe factors associated with survival in Alzheimer disease (AD) in a multiethnic, population-based longitudinal study. Methods: AD cases were identified in the Washington Heights Inwood Columbia Aging Project, a longitudinal, community-based study of cognitive aging in Northern Manhattan. The sample comprised 323 participants who were initially dementia-free but developed AD during study follow-up (incident cases). Participants were followed for an average of 4.1 (up to 12.6) years. Possible factors associated with shorter lifespan were assessed using Cox proportional hazards models with attained age as the time to event (time from birth to death or last follow-up). In subanalyses, median postdiagnosis survival durations were estimated using postdiagnosis study follow-up as the timescale. Results: The mortality rate was 10.7 per 100 person-years. Mortality rates were higher among those diagnosed at older ages, and among Hispanics compared to non-Hispanic whites. The median lifespan of the entire sample was 92.2 years (95% CI: 90.3, 94.1). In a multivariable-adjusted Cox model, history of diabetes and history of hypertension were independently associated with a shorter lifespan. No differences in lifespan were seen by race/ethnicity after multivariable adjustment. The median postdiagnosis survival duration was 3.7 years among non-Hispanic whites, 4.8 years among African Americans, and 7.6 years among Hispanics. Conclusion: Factors influencing survival in Alzheimer disease include race/ethnicity and comorbid diabetes and hypertension. GLOSSARY AD = Alzheimer disease; NDI = National Death Index; WHICAP = Washington Heights Inwood Columbia Aging Project. PMID:18981370

Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

PubMed

Palmer, M; Belch, A; Hanson, J; Brox, L

1989-01-01

The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose.

Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.

PubMed Central

Palmer, M.; Belch, A.; Hanson, J.; Brox, L.

1989-01-01

The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose. PMID:2757916

Differential effects of smoking on lung cancer mortality before and after household stove improvement in Xuanwei, China.

PubMed

Lee, K-M; Chapman, R S; Shen, M; Lubin, J H; Silverman, D T; He, X; Hosgood, H D; Chen, B E; Rajaraman, P; Caporaso, N E; Fraumeni, J F; Blair, A; Lan, Q

2010-08-24

In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China. We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement. We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.

PubMed

Lobato, Robert L; White, William D; Mathew, Joseph P; Newman, Mark F; Smith, Peter K; McCants, Charles B; Alexander, John H; Podgoreanu, Mihai V

2011-09-13

We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality after coronary artery bypass graft (CABG) surgery. Two separate cohorts of patients undergoing CABG surgery at a single institution were examined, and all-cause mortality between 30 days and 5 years after the index CABG was ascertained from the National Death Index. In a discovery cohort of 1018 patients, a panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes was tested with Cox proportional hazard models to identify clinical and genomic multivariate predictors of incident death. After adjustment for multiple comparisons and clinical predictors of mortality, the homozygote minor allele of a common variant in the thrombomodulin (THBD) gene (rs1042579) was independently associated with significantly increased risk of all-cause mortality (hazard ratio, 2.26; 95% CI, 1.31 to 3.92; P=0.003). Six tag SNPs in the THBD gene, 1 of which (rs3176123) in complete linkage disequilibrium with rs1042579, were then assessed in an independent validation cohort of 930 patients. After multivariate adjustment for the clinical predictors identified in the discovery cohort and multiple testing, the homozygote minor allele of rs3176123 independently predicted all-cause mortality (hazard ratio, 3.6; 95% CI, 1.67 to 7.78; P=0.001). In 2 independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk after CABG and significantly improve the classification ability of traditional postoperative mortality prediction models.

A prospective study of caffeine intake and risk of incident tinnitus.

PubMed

Glicksman, Jordan T; Curhan, Sharon G; Curhan, Gary C

2014-08-01

Caffeine is a commonly consumed substance that has been thought to play a role in the development of tinnitus, but prospective data are lacking. We prospectively evaluated the association between caffeine intake and self-reported tinnitus in a female cohort. Participants were 65,085 women in the Nurses' Health Study II, aged 30 to 44 years and without tinnitus at baseline in 1991, who completed questionnaires about lifestyle and medical history every 2 years and food frequency questionnaires every 4 years. Information on self-reported tinnitus and date of onset was obtained from the 2009 questionnaire, with cases defined as those reporting experiencing symptoms "a few days/week" or "daily." Multivariable adjusted hazard ratios were calculated using Cox proportional hazards regression models. At baseline, the mean age of the cohort was 36.3 years and the mean caffeine intake was 242.3 mg/d. After 18 years of follow-up, 5289 incident cases of tinnitus were reported. There was a significant inverse association between caffeine intake and the incidence of tinnitus. Compared with women with caffeine intake less than 150 mg/d (150 mg corresponds to ∼ one 8-ounce cup of coffee), the multivariable adjusted hazard ratios were 0.85 (95% confidence interval, 0.76-0.95) for those who consumed 450 to 599 mg/d and 0.79 (0.68-0.91) for those who consumed 600 mg/d or more. In this prospective study, higher caffeine intake was associated with a lower risk of incident tinnitus in women. Copyright © 2014 Elsevier Inc. All rights reserved.

 Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

PubMed

Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

2016-01-01

 Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

Appendectomy correlates with increased risk of pyogenic liver abscess

PubMed Central

Liao, Kuan-Fu; Lai, Shih-Wei; Lin, Cheng-Li; Chien, Sou-Hsin

2016-01-01

Abstract Little is known on the association between appendectomy and pyogenic liver abscess. The objective of this study was to investigate the association between appendectomy and the risk of pyogenic liver abscess in Taiwan. This population-based retrospective cohort study was conducted using the hospitalization dataset of the Taiwan National Health Insurance Program. There were 212,530 subjects age 20 to 84 years with newly diagnosed appendectomy as the appendectomy group since 1998 to 2010, and 850,099 randomly selected subjects without appendectomy as the nonappendectomy group. Both appendectomy and nonappendectomy groups were matched with sex, age, comorbidities, and index year of diagnosing appendectomy. The incidence of pyogenic liver abscess at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was applied to investigate the hazard ratio (HR) and 95% confidence interval (CI) for risk of pyogenic liver abscess associated with appendectomy and other comorbidities including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus. The overall incidence of pyogenic liver abscess was 1.73-fold greater in the appendectomy group than that in the nonappendectomy group (3.85 vs 2.22 per 10,000 person-years, 95% CI 1.71, 1.76). The multivariable regression analysis disclosed that the adjusted HR of pyogenic liver abscess was 1.77 for the appendectomy group (95% CI 1.59, 1.97), when compared with the nonappendectomy group. Appendectomy is associated with increased hazard of pyogenic liver abscess. Further studies remain necessary to confirm our findings. PMID:27368018

LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

PubMed

Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

2016-06-01

This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort

PubMed Central

Budhathoki, Sanjeev; Hidaka, Akihisa; Sawada, Norie; Tanaka-Mizuno, Sachiko; Kuchiba, Aya; Charvat, Hadrien; Goto, Atsushi; Kojima, Satoshi; Sudo, Natsuki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro; Iwasaki, Motoki

2018-01-01

Abstract Objective To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. Design Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. Setting Nine public health centre areas across Japan. Participants 3301 incident cases of cancer and 4044 randomly selected subcohort participants. Exposure Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. Main outcome measure Incidence of overall or site specific cancer. Results Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. Conclusions In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites. PMID:29514781

The Application of Extended Cox Proportional Hazard Method for Estimating Survival Time of Breast Cancer

NASA Astrophysics Data System (ADS)

Husain, Hartina; Astuti Thamrin, Sri; Tahir, Sulaiha; Mukhlisin, Ahmad; Mirna Apriani, M.

2018-03-01

Breast cancer is one type of cancer that is the leading cause of death worldwide. This study aims to model the factors that affect the survival time and rate of cure of breast cancer patients. The extended cox model, which is a modification of the proportional hazard cox model in which the proportional hazard assumptions are not met, is used in this study. The maximum likelihood estimation approach is used to estimate the parameters of the model. This method is then applied to medical record data of breast cancer patient in 2011-2016, which is taken from Hasanuddin University Education Hospital. The results obtained indicate that the factors that affect the survival time of breast cancer patients are malignancy and leukocyte levels.

Body mass index and mortality in patients with type 2 diabetes mellitus: A prospective cohort study of 11,449 participants.

PubMed

Liu, Hui; Wu, Shouling; Li, Yun; Sun, Lixia; Huang, Zhe; Lin, Liming; Liu, Yan; Ji, Chunpeng; Zhao, Hualing; Li, Chunhui; Song, Lu; Cong, Hongliang

2017-02-01

To investigate the association between body-mass index and mortality in Chinese adults T2DM. 11,449 participants of Kailuan Study with T2DM were included in this prospective cohort study. All-cause mortality was calculated using Kaplan-Meier analysis. Cox proportional hazards analysis was used to estimate the association between BMI and mortality. During a mean follow-up period of 7.25±1.42years, 1254 deaths occurred. The number of deaths of the underweight, normal weight, overweight, and obese group was 23, 389, 557, and 285; the corresponding mortality was 25.0%, 13.4%, 10.3%, and 9.4%, respectively. The obese group had the lowest all-cause mortality rate (log-rank chi-square=48.430, P<0.001). After adjusting for age, sex, fasting blood glucose, smoking status, systolic blood pressure, history of hypertension, stroke, cancer and myocardial infarction, compared with the normal weight group, Multivariate Cox proportional hazard regression analysis showed that HR (95% CI) of all-cause mortality in the underweight, overweight, and obese group was 1.497 (0.962, 2.330), 0.833 (0.728, 0.952), and 0.809 (0.690, 0.949). After stratifying for age tertiles, this trend remained. In T2DM patients in north China, the risk for all-cause mortality was lower in the overweight and the obese groups than those in the normal weight and the underweight groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Impact of Emphysema Evaluated by High-Resolution Computed Tomography on Idiopathic Pulmonary Fibrosis Diagnosed by Surgical Lung Biopsy.

PubMed

Kohashi, Yasuo; Arai, Toru; Sugimoto, Chikatoshi; Tachibana, Kazunobu; Akira, Masanori; Kitaichi, Masanori; Hayashi, Seiji; Inoue, Yoshikazu

2016-01-01

The prognosis of combined cases of pulmonary fibrosis and emphysema is unresolved partially because radiological differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia is difficult in coexisting emphysema cases. The purpose of this study was to clarify the clinical impact of emphysema on the survival of patients with idiopathic pulmonary fibrosis (IPF). One hundred and seven patients with interstitial lung diseases were diagnosed by surgical lung biopsies between 2006 and 2012, and 47 patients were diagnosed with IPF through multidisciplinary discussion. Emphysema on high-resolution computed tomography scans was evaluated semiquantitatively by visual scoring. Eight out of the 47 IPF patients showed a higher emphysema score (>3) and were diagnosed to have IPF-emphysema. The median survival time of patients with IPF-emphysema (1,734 days) from the initial diagnosis was significantly shorter than that of patients with IPF alone (2,229 days) by Kaplan-Meier analysis (p = 0.007, log-rank test). Univariate Cox proportional hazard regression analyses revealed that a higher total emphysema score (>3.0) was a significantly poor prognostic factor in addition to Krebs von den Lungen-6, surfactant protein-D, arterial oxygen tension, percent forced vital capacity, and percent diffusing capacity of carbon monoxide (%DLCO). Multivariate Cox proportional hazard regression analyses with the stepwise method showed that higher total emphysema score (>3) and %DLCO were significantly poor prognostic factors. The prognosis of IPF-emphysema was significantly worse than that of IPF alone. © 2016 S. Karger AG, Basel.

Risk Stratification of Patients With Current Generation Continuous-Flow Left Ventricular Assist Devices Being Bridged to Heart Transplantation.

PubMed

Guha, Ashrith; Nguyen, Duc; Cruz-Solbes, Ana S; Amione-Guerra, Javier; Schutt, Robert C; Bhimaraj, Arvind; Trachtenberg, Barry H; Park, Myung H; Graviss, Edward A; Gaber, Osama; Suarez, Erik; Montane, Eva; Torre-Amione, Guillermo; Estep, Jerry D

Patients bridged to transplant (BTT) with continuous-flow left ventricular assist devices (CF-LVADs) have increased in the past decade. Decision support tools for these patients are limited. We developed a risk score to estimate prognosis and guide decision-making. We included heart transplant recipients bridged with CF-LVADs from the United Network for Organ Sharing (UNOS) database and divided them into development (2,522 patients) and validation cohorts (1,681 patients). Univariate and multivariate Cox proportional hazards models were performed. Variables that independently predicted outcomes (age, African American race, recipient body mass index [BMI], intravenous [IV] antibiotic use, pretransplant dialysis, and total bilirubin) were assigned weight using linear transformation, and risk scores were derived. Patients were grouped by predicted posttransplant mortality: low risk (≤ 38 points), medium risk (38-41 points), and high risk (≥ 42 points). We performed Cox proportional hazards analysis on wait-listed CF-LVAD patients who were not transplanted. Score significantly discriminated survival among the groups in the development cohort (6.7, 12.9, 20.7; p = 0.001), validation cohort (6.4, 10.1, 13.6; p < 0.001), and ambulatory cohort (6.4, 11.5, 17.2; p < 0.001). We derived a left ventricular assist device (LVAD) BTT risk score that effectively identifies CF-LVAD patients who are at higher risk for worse outcomes after heart transplant. This score may help physicians weigh the risks of transplantation in patients with CF-LVAD.

Cumulative HIV viremia during highly active antiretroviral therapy is a strong predictor of AIDS-related lymphoma.

PubMed

Zoufaly, Alexander; Stellbrink, Hans-Jürgen; Heiden, Matthias An der; Kollan, Christian; Hoffmann, Christian; van Lunzen, Jan; Hamouda, Osamah

2009-07-01

AIDS-related lymphoma contributes to significant morbidity and mortality among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). We assessed the predictive role of cumulative HIV viremia and other risk factors in the development of AIDS-related non-Hodgkin lymphoma. Data from the Clinical Surveillance of HIV Disease (ClinSurv) study, an ongoing, observational, open cohort study of HIV-infected patients from different urban areas in Germany, were analyzed using a Cox proportional hazards model. In the Cox model, which comprised 6022 patients and 27,812 patient-years of follow-up while patients were receiving HAART from 1999 through 2006, cumulative HIV viremia was found to be independently associated with the risk of lymphoma (hazard ratio, [HR], 1.67 [95% confidence interval {CI}, 1.27-2.20]) (P < .001]). This association differed markedly between lymphoma subtypes. Although the association was more pronounced for Burkitt-type lymphoma (HR, 3.45 [95% CI, 1.52-7.85]) (P = .003), there was no association between cumulative HIV viremia and the incidence of primary central nervous system lymphoma (HR, 1.00 [95% CI, 0.39-2.57]) (P = .997). Other risk factors associated with an increased risk in a multivariable analysis included the latest CD4 T cell count as well as age per 10-year increment. Cumulative HIV viremia is an independent and strong predictor of AIDS-related lymphoma among patients receiving HAART. The influence of cumulative HIV viremia may differ between lymphoma subtypes.

Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.

PubMed

Braadland, Peder R; Giskeødegård, Guro; Sandsmark, Elise; Bertilsson, Helena; Euceda, Leslie R; Hansen, Ailin F; Guldvik, Ingrid J; Selnæs, Kirsten M; Grytli, Helene H; Katz, Betina; Svindland, Aud; Bathen, Tone F; Eri, Lars M; Nygård, Ståle; Berge, Viktor; Taskén, Kristin A; Tessem, May-Britt

2017-11-21

Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan-Meier survival analyses and concordance index (C-index). High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P=0.016 and C-index: 0.765; HR: 1.43; P=0.014, respectively). Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.

Prediction of Mortality with A Body Shape Index in Young Asians: Comparison with Body Mass Index and Waist Circumference.

PubMed

Lee, Da-Young; Lee, Mi-Yeon; Sung, Ki-Chul

2018-06-01

This paper investigated the impact of A Body Shape Index (ABSI) on the risk of all-cause mortality compared with the impact of waist circumference (WC) and body mass index (BMI). This paper reviewed data of 213,569 Korean adults who participated in health checkups between 2002 and 2012 at Kangbuk Samsung Hospital in Seoul, Korea. A multivariate Cox proportional hazard analysis was performed on the BMI, WC, and ABSI z score continuous variables as well as quintiles. During 1,168,668.7 person-years, 1,107 deaths occurred. As continuous variables, a significant positive relationship with the risk of all-cause death was found only in ABSI z scores after adjustment for age, sex, current smoking, alcohol consumption, regular exercise, presence of diabetes or hypertension, and history of cardiovascular diseases. In Cox analysis of quintiles, quintile 5 of the ABSI z score showed significantly increased hazard ratios (HRs) for mortality risk (HR [95% CI] was 1.32 [1.05-1.66]), whereas the risk for all-cause mortality, on the other hand, decreased in quintiles 3 through 5 of BMI and WC compared with their first quintiles after adjusting for several confounders. This study showed that the predictive value of ABSI for mortality risk was strong for a sample of young Asian participants and that its usefulness was better than BMI or WC. © 2018 The Obesity Society.

Vitamin D and the risk of dementia and Alzheimer disease.

PubMed

Littlejohns, Thomas J; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Fried, Linda; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Kos, Katarina; Soni, Maya; Llewellyn, David J

2014-09-02

To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. © 2014 American Academy of Neurology.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, James X.; Rose, Steven; White, Sarah B.

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Coxmore » proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.« less

Serum and Dietary Potassium and Risk of Incident Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Chatterjee, Ranee; Yeh, Hsin-Chieh; Shafi, Tariq; Selvin, Elizabeth; Anderson, Cheryl; Pankow, James S.; Miller, Edgar; Brancati, Frederick

2012-01-01

Background Serum potassium levels affect insulin secretion by pancreatic beta-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes, independent of diuretic use. Methods We analyzed data from 12,209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an on-going prospective cohort study beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the relative hazard (RH) of incident diabetes associated with baseline serum potassium levels. Results During 9 years of in-person follow-up, 1475 participants developed incident diabetes. In multivariate analyses, we found an inverse association between serum potassium and risk of incident diabetes. Compared to those with a high-normal serum potassium (5.0-5.5 mEq/l), adults with serum potassium levels of < 4.0, 4.0-<4.5, and 4.5-<5.0, (mEq/L) had adjusted relative hazards (RH) (95% CI) of incident diabetes of 1.64 (1.29-2.08), 1.64 (1.34-2.01), and 1.39 (1.14-1.71) respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with RHs of 1.2-1.3 for those with a serum potassium less than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident diabetes in unadjusted models but not in multivariate models. Conclusions Serum potassium is an independent predictor of incident diabetes in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of diabetes. PMID:20975023

Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated metastatic melanoma patients.

PubMed

Failing, Jarrett J; Yan, Yiyi; Porrata, Luis F; Markovic, Svetomir N

2017-12-01

The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with prognosis in many malignancies including metastatic melanoma. However, it has not been studied in patients treated with immune checkpoint inhibitors. In this study, we analyzed the baseline LMR with progression-free survival (PFS) and overall survival (OS) in metastatic melanoma patients treated with pembrolizumab. A total of 133 patients with metastatic melanoma treated with pembrolizumab were included in this retrospective study. LMR was calculated from pretherapy peripheral blood counts and the optimal cutoff value was determined by a receiver operator characteristic curve. PFS and OS were evaluated using the Kaplan-Meier method and multivariate Cox proportional hazard modeling. Patients with an LMR of at least 1.7 showed improved PFS (hazard ratio=0.55; 95% confidence interval: 0.34-0.92; P=0.024) and OS (hazard ratio=0.29; 95% confidence interval: 0.15-0.59; P=0.0007). The baseline LMR is associated with PFS and OS in metastatic melanoma patients treated with pembrolizumab, and could represent a convenient and cost-effective prognostic biomarker. Validation of these findings in an independent cohort is needed.

Validation of methods to control for immortal time bias in a pharmacoepidemiologic analysis of renin-angiotensin system inhibitors in type 2 diabetes.

PubMed

Yang, Xilin; Kong, Alice Ps; Luk, Andrea Oy; Ozaki, Risa; Ko, Gary Tc; Ma, Ronald Cw; Chan, Juliana Cn; So, Wing Yee

2014-01-01

Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin-angiotensin system (RAS) inhibitors as the reference cardioprotective drug. We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68-1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes.

Refusal of postoperative radiotherapy and its association with survival in head and neck cancer.

PubMed

Schwam, Zachary G; Husain, Zain; Judson, Benjamin L

2015-11-01

Administering postoperative radiotherapy (PORT) is associated with improved survival and slower disease progression in select head and neck cancer patients. Predictive factors for PORT refusal have not been described in this population. Retrospective analysis of 6127 head and neck cancer patients who received or refused PORT in the National Cancer Database (2003-2006) was performed. Statistical analysis included Chi-square, multivariable logistic regression, Kaplan-Meier, and Cox proportional hazards analysis. In total, 247 patients (4.0%) refused PORT. Three-year overall survival was 62.8% versus 53.4% for those who received and refused PORT, respectively. PORT refusers were more likely to have negative nodes than those who underwent PORT (37.4% versus 20.1%, p<.001). In multivariate analysis, predictive factors for refusing PORT included living far from the treatment facility (OR 1.92), having negative nodes (OR 2.14), and Charlson score of ⩾ 2 (OR 2.14) (all p ⩽.001). PORT refusal was associated with increased mortality (hazard ratio 1.20, p=.044). A significant proportion of head and neck cancer patients refused PORT; this was associated with compromised overall survival. Predictive factors for PORT refusal included socioeconomic, demographic, and pathologic variables. Elucidating root causes of refusal may lead to interventions that improve long-term outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Smoking is a risk factor for pulmonary metastasis in colorectal cancer.

PubMed

Yahagi, M; Tsuruta, M; Hasegawa, H; Okabayashi, K; Toyoda, N; Iwama, N; Morita, S; Kitagawa, Y

2017-09-01

The hepatic microenvironment, which may include chronic inflammation and fibrosis, is considered to contribute to the pathogenesis of liver metastases of colorectal cancer. A similar mechanism is anticipated for pulmonary metastases, although no reports are available. Smoking causes pulmonary inflammation and fibrosis. Thus, we hypothesized that smokers would be especially affected by pulmonary metastases of colorectal cancer. In this study, we attempted to clarify the impact of smoking on pulmonary metastasis of colorectal cancer. Between September 2005 and December 2010 we reviewed 567 patients with pathological Stage I, II or III colorectal cancer, whose clinicopathological background included a preoperative smoking history, pack-year history from medical records. Univariate and multivariate analyses using the Cox proportional hazard model were performed to determine the independent prognostic factors for pulmonary metastasis-free survival. Pulmonary metastases occurred in 39 (6.9%) patients. The smoking histories revealed 355 never smokers, 119 former smokers and 93 current smokers among the subjects. Multivariate analysis revealed that being a current smoker (hazard ratio = 2.72, 95% CI 1.18-6.25; P = 0.02) was an independent risk factor for pulmonary metastases. Smoking may be a risk factor for pulmonary metastasis of colorectal cancer. Cessation of smoking should be recommended to prevent pulmonary metastasis, although further basic and clinical studies are required. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Relationship between specific adverse events and efficacy of exemestane therapy in early postmenopausal breast cancer patients.

PubMed

Fontein, D B Y; Houtsma, D; Hille, E T M; Seynaeve, C; Putter, H; Meershoek-Klein Kranenbarg, E; Guchelaar, H J; Gelderblom, H; Dirix, L Y; Paridaens, R; Bartlett, J M S; Nortier, J W R; van de Velde, C J H

2012-12-01

Many adverse events (AEs) associated with aromatase inhibitors (AIs) involve symptoms related to the depletion of circulating estrogens, and may be related to efficacy. We assessed the relationship between specific AEs [hot flashes (HF) and musculoskeletal AEs (MSAE)] and survival outcomes in Dutch and Belgian patients treated with exemestane (EXE) in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Additionally, the relationship between hormone receptor expression and AEs was assessed. Efficacy end points were relapse-free survival (RFS), overall survival (OS) and breast cancer-specific mortality (BCSM), starting at 6 months after starting EXE treatment. AEs reported in the first 6 months of treatment were included. Specific AEs comprised HF and/or MSAE. Landmark analyses and Cox proportional hazards models assessed survival differences up to 5 years. A total of 1485 EXE patients were included. Patients with HF had a better RFS than patients without HF [multivariate hazard ratio (HR) 0.393, 95% confidence interval (CI) 0.19-0.813; P = 0.012]. The occurrence of MSAE versus no MSAE did not relate to better RFS (multivariate HR 0.677, 95% CI 0.392-1.169; P = 0.162). Trends were maintained for OS and BCSM. Quantitative hormone receptor expression was not associated with specific AEs. Some AEs associated with estrogen depletion are related to better outcomes and may be valuable biomarkers in AI treatment.

Risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors.

PubMed

Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2014-09-01

The aim of this study was to identify risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors (BOTs). We performed a retrospective review of all patients treated and followed for BOTs between 1996 and 2011. Multivariate Cox proportional hazards model analysis was performed to identify independent risk factors for progression to invasive carcinoma. A total of 364 patients were identified. During the median follow-up of 53.8 months, 31 patients (8.5%) developed recurrent disease: 12 (3.3%) had recurrent disease with progression to invasive carcinoma, and 19 (5.2%) had recurrent disease with borderline histology. Disease-related deaths (7/364; 1.7%) were observed only in patients with progression to invasive carcinoma. The multivariate analysis showed that independent risk factors for progression to invasive carcinoma were advanced disease stage (hazard ratio [HR], 5.59; P = 0.005), age 65 years or older (HR, 5.13; P = 0.037), and the presence of microinvasion (HR, 3.71; P = 0.047). These 3 factors were also independently related to overall survival. Although patients with BOTs have an excellent prognosis, the risk of progression to invasive carcinoma and thereby death remains. Therefore, physicians should pay closer attention to BOT patients with these risk factors (ie, advanced disease stage, old age, and microinvasion), and more careful surveillance for progression to invasive carcinoma is needed.

Augmenting the logrank test in the design of clinical trials in which non-proportional hazards of the treatment effect may be anticipated.

PubMed

Royston, Patrick; Parmar, Mahesh K B

2016-02-11

Most randomized controlled trials with a time-to-event outcome are designed assuming proportional hazards (PH) of the treatment effect. The sample size calculation is based on a logrank test. However, non-proportional hazards are increasingly common. At analysis, the estimated hazards ratio with a confidence interval is usually presented. The estimate is often obtained from a Cox PH model with treatment as a covariate. If non-proportional hazards are present, the logrank and equivalent Cox tests may lose power. To safeguard power, we previously suggested a 'joint test' combining the Cox test with a test of non-proportional hazards. Unfortunately, a larger sample size is needed to preserve power under PH. Here, we describe a novel test that unites the Cox test with a permutation test based on restricted mean survival time. We propose a combined hypothesis test based on a permutation test of the difference in restricted mean survival time across time. The test involves the minimum of the Cox and permutation test P-values. We approximate its null distribution and correct it for correlation between the two P-values. Using extensive simulations, we assess the type 1 error and power of the combined test under several scenarios and compare with other tests. We investigate powering a trial using the combined test. The type 1 error of the combined test is close to nominal. Power under proportional hazards is slightly lower than for the Cox test. Enhanced power is available when the treatment difference shows an 'early effect', an initial separation of survival curves which diminishes over time. The power is reduced under a 'late effect', when little or no difference in survival curves is seen for an initial period and then a late separation occurs. We propose a method of powering a trial using the combined test. The 'insurance premium' offered by the combined test to safeguard power under non-PH represents about a single-digit percentage increase in sample size. The combined test increases trial power under an early treatment effect and protects power under other scenarios. Use of restricted mean survival time facilitates testing and displaying a generalized treatment effect.

The Effect of the Multivariate Box-Cox Transformation on the Power of MANOVA.

ERIC Educational Resources Information Center

Kirisci, Levent; Hsu, Tse-Chi

Most of the multivariate statistical techniques rely on the assumption of multivariate normality. The effects of non-normality on multivariate tests are assumed to be negligible when variance-covariance matrices and sample sizes are equal. Therefore, in practice, investigators do not usually attempt to remove non-normality. In this simulation…

Multivariate analysis of risk factors for long-term urethroplasty outcome.

PubMed

Breyer, Benjamin N; McAninch, Jack W; Whitson, Jared M; Eisenberg, Michael L; Mehdizadeh, Jennifer F; Myers, Jeremy B; Voelzke, Bryan B

2010-02-01

We studied the patient risk factors that promote urethroplasty failure. Records of patients who underwent urethroplasty at the University of California, San Francisco Medical Center between 1995 and 2004 were reviewed. Cox proportional hazards regression analysis was used to identify multivariate predictors of urethroplasty outcome. Between 1995 and 2004, 443 patients of 495 who underwent urethroplasty had complete comorbidity data and were included in analysis. Median patient age was 41 years (range 18 to 90). Median followup was 5.8 years (range 1 month to 10 years). Stricture recurred in 93 patients (21%). Primary estimated stricture-free survival at 1, 3 and 5 years was 88%, 82% and 79%. After multivariate analysis smoking (HR 1.8, 95% CI 1.0-3.1, p = 0.05), prior direct vision internal urethrotomy (HR 1.7, 95% CI 1.0-3.0, p = 0.04) and prior urethroplasty (HR 1.8, 95% CI 1.1-3.1, p = 0.03) were predictive of treatment failure. On multivariate analysis diabetes mellitus showed a trend toward prediction of urethroplasty failure (HR 2.0, 95% CI 0.8-4.9, p = 0.14). Length of urethral stricture (greater than 4 cm), prior urethroplasty and failed endoscopic therapy are predictive of failure after urethroplasty. Smoking and diabetes mellitus also may predict failure potentially secondary to microvascular damage. Copyright 2010 American Urological Association. Published by Elsevier Inc. All rights reserved.

Regularization Paths for Cox's Proportional Hazards Model via Coordinate Descent.

PubMed

Simon, Noah; Friedman, Jerome; Hastie, Trevor; Tibshirani, Rob

2011-03-01

We introduce a pathwise algorithm for the Cox proportional hazards model, regularized by convex combinations of ℓ 1 and ℓ 2 penalties (elastic net). Our algorithm fits via cyclical coordinate descent, and employs warm starts to find a solution along a regularization path. We demonstrate the efficacy of our algorithm on real and simulated data sets, and find considerable speedup between our algorithm and competing methods.

Extended cox regression model: The choice of timefunction

NASA Astrophysics Data System (ADS)

Isik, Hatice; Tutkun, Nihal Ata; Karasoy, Durdu

2017-07-01

Cox regression model (CRM), which takes into account the effect of censored observations, is one the most applicative and usedmodels in survival analysis to evaluate the effects of covariates. Proportional hazard (PH), requires a constant hazard ratio over time, is the assumptionofCRM. Using extended CRM provides the test of including a time dependent covariate to assess the PH assumption or an alternative model in case of nonproportional hazards. In this study, the different types of real data sets are used to choose the time function and the differences between time functions are analyzed and discussed.

Development of a multivariate model to predict the likelihood of carcinoma in patients with indeterminate peripheral lung nodules after a nondiagnostic bronchoscopic evaluation.

PubMed

Voss, Jesse S; Iqbal, Seher; Jenkins, Sarah M; Henry, Michael R; Clayton, Amy C; Jett, James R; Kipp, Benjamin R; Halling, Kevin C; Maldonado, Fabien

2014-01-01

Studies have shown that fluorescence in situ hybridization (FISH) testing increases lung cancer detection on cytology specimens in peripheral nodules. The goal of this study was to determine whether a predictive model using clinical features and routine cytology with FISH results could predict lung malignancy after a nondiagnostic bronchoscopic evaluation. Patients with an indeterminate peripheral lung nodule that had a nondiagnostic bronchoscopic evaluation were included in this study (N = 220). FISH was performed on residual bronchial brushing cytology specimens diagnosed as negative (n = 195), atypical (n = 16), or suspicious (n = 9). FISH results included hypertetrasomy (n = 30) and negative (n = 190). Primary study end points included lung cancer status along with time to diagnosis of lung cancer or date of last clinical follow-up. Hazard ratios (HRs) were calculated using Cox proportional hazards regression model analyses, and P values < .05 were considered statistically significant. The mean age of the 220 patients was 66.7 years (range, 35-91), and most (58%) were men. Most patients (79%) were current or former smokers with a mean pack year history of 43.2 years (median, 40; range, 1-200). After multivariate analysis, hypertetrasomy FISH (HR = 2.96, P < .001), pack years (HR = 1.03 per pack year up to 50, P = .001), age (HR = 1.04 per year, P = .02), atypical or suspicious cytology (HR = 2.02, P = .04), and nodule spiculation (HR = 2.36, P = .003) were independent predictors of malignancy over time and were used to create a prediction model (C-statistic = 0.78). These results suggest that this multivariate model including test results and clinical features may be useful following a nondiagnostic bronchoscopic examination. © 2013.

The Risk of Achilles or Biceps Tendon Rupture in New Statin Users: A Propensity Score-Matched Sequential Cohort Study.

PubMed

Spoendlin, Julia; Layton, J Bradley; Mundkur, Mallika; Meier, Christian; Jick, Susan S; Meier, Christoph R

2016-12-01

Case reports and pharmacovigilance data reported cases of tendon ruptures in statin users, but evidence from observational studies is scarce and inconclusive. We aimed to assess the association between new statin use and tendon rupture. We performed a propensity score (PS)-matched sequential cohort study, using data from the Clinical Practice Research Datalink. Patients aged ≥45 years with at least one new statin prescription between 1995 and 2014 were PS-matched within 2-year entry blocks to patients without a statin prescription during the block. We followed patients until they had a recorded Achilles or biceps tendon rupture, completed 5 years of follow-up, or were censored for change in exposure status or another censoring criterion. We calculated hazard ratios (HRs) with 95 % confidence intervals (CIs), applying Cox proportional hazard analyses in the overall cohort (crude and multivariable) and in the PS-matched cohort. We performed subgroup analyses by sex, age, treatment duration, and statin dose. We observed a crude HR of 1.32 (95 % CI 1.21-1.44) in the overall cohort, which attenuated after multivariable adjustment (HR 1.02, 95 % CI 0.92-1.12) and after PS-matching (HR 0.95, 95 % CI 0.84-1.08). Crude HRs were higher in women than in men, but remained around null in both sexes after multivariable adjustment and PS-matching. Subgroup analyses by age, treatment duration, and statin dose revealed null results across all subgroups. The results of this cohort study suggest that statin use does not increase the risk of tendon rupture, irrespective of gender, age, statin dose, or treatment duration.

Relation of Pericardial Fat, Intrathoracic Fat, and Abdominal Visceral Fat with Incident Atrial Fibrillation (From the Framingham Heart Study)

PubMed Central

Lee, Jane J.; Yin, Xiaoyan; Hoffmann, Udo; Fox, Caroline S.; Benjamin, Emelia J.

2016-01-01

Obesity is associated with increased risk of developing atrial fibrillation (AF). Different fat depots may have differential associations with cardiac pathology. We examined the longitudinal associations between pericardial, intrathoracic, and visceral fat with incident AF. We studied Framingham Heart Study Offspring and Third Generation Cohorts who participated in the multi-detector computed tomography sub-study examination 1. We constructed multivariable-adjusted Cox proportional hazard models for risk of incident AF. Body mass index (BMI) was included in the multivariable-adjusted model as a secondary adjustment. We included 2,135 participants (53.3% women; mean age 58.8 years). During a median follow-up of 9.7 years, we identified 162 cases of incident AF. Across the increasing tertiles of pericardial fat volume, age- and sex-adjusted incident AF rate per 1000 person-years of follow-up were 8.4, 7.5, and 10.2. Based on an age- and sex-adjusted model, greater pericardial fat [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.03-1.34] and intrathoracic fat (HR 1.24, 95% CI 1.06-1.45) were associated with increased risk of incident AF. The HRs (95% CI) for incident AF were 1.13 (0.99-1.30) for pericardial fat, 1.19 (1.01-1.40) for intrathoracic fat, and 1.09 (0.93-1.28) for abdominal visceral fat after multivariable adjustment. After additional adjustment of BMI, none of the associations remained significant (all p>0.05). Our findings suggest that cardiac ectopic fat depots may share common risk factors with AF, which may have led to a lack of independence in the association between pericardial fat with incident AF. PMID:27666172

Demographic and lifestyle factors and survival among patients with esophageal and gastric cancer: The Biobank Japan Project.

PubMed

Okada, Emiko; Ukawa, Shigekazu; Nakamura, Koshi; Hirata, Makoto; Nagai, Akiko; Matsuda, Koichi; Ninomiya, Toshiharu; Kiyohara, Yutaka; Muto, Kaori; Kamatani, Yoichiro; Yamagata, Zentaro; Kubo, Michiaki; Nakamura, Yusuke; Tamakoshi, Akiko

2017-03-01

Several studies have evaluated associations between the characteristics of patients with esophageal and gastric cancer and survival, but these associations remain unclear. We described the distribution of demographic and lifestyle factors among patients with esophageal and gastric cancer in Japan, and investigated their potential effects on survival. Between 2003 and 2007, 24- to 95-year-old Japanese patients with esophageal and gastric cancer were enrolled in the BioBank Japan Project. The analysis included 365 patients with esophageal squamous cell carcinoma (ESCC) and 1574 patients with gastric cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using medical institution-stratified Cox proportional hazards models. During follow-up, 213 patients with ESCC (median follow-up, 4.4 years) and 603 patients with gastric cancer (median follow-up, 6.1 years) died. Among patients with ESCC, the mortality risk was higher in ever drinkers versus never drinkers (multivariable HR = 2.37, 95% CI: 1.24, 4.53). Among patients with gastric cancer, the mortality risk was higher in underweight patients versus patients of normal weight (multivariable HR = 1.66, 95% CI: 1.34, 2.05). Compared to patients with gastric cancer with no physical exercise habit, those who exercised ≥3 times/week had a lower mortality risk (multivariate HR = 0.75, 95% CI = 0.61, 0.93). However, lack of stage in many cases was a limitation. Among patients with ESCC, alcohol drinkers have a poor prognosis. Patients with gastric cancer who are underweight also have a poor prognosis, whereas patients with physical exercise habits have a good prognosis. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Comparisons of sleep apnoea rate and outcomes among patients with resistant and non-resistant hypertension.

PubMed

Bhandari, Simran K; Shi, Jiaxiao; Molnar, Miklos Z; Rasgon, Scott A; Derose, Stephen F; Kovesdy, Csaba P; Calhoun, David A; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J; Sim, John J

2016-11-01

We directly compared sleep apnoea (SA) rates and risk of cardiovascular and mortality outcomes among SA patients with resistant hypertension (RH) and non-RH within a large diverse hypertension population. A retrospective cohort study between 1 January 2006 and 31 December 2010 among hypertensive adults (age ≥ 18 years) was performed within an integrated health system. Rates of SA in RH and non-RH were determined. Multivariable logistic regression analyses were used to calculate OR for SA. Cox proportional hazard modelling was used to estimate hazard ratios (HRs) for cardiovascular and mortality outcomes between SA in RH versus SA in non-RH adjusting for age, gender, race, BMI, chronic kidney disease and other comorbidities. SA was identified in 33 682 (7.2%) from 470 386 hypertensive individuals. SA in RH accounted for 5806 (9.6%) compared to SA in non-RH 27 876 individuals (6.8%). Multivariable OR (95% CI) for SA was 1.16 (1.12, 1.19), 3.57 (3.47, 3.66) and 2.20 (2.15, 2.25) for RH versus non-RH, BMI ≥ 30, and males, respectively. Compared to SA in non-RH individuals, SA in RH had a multivariable adjusted HR (95% CI) of 1.24 (1.13, 1.36), 1.43 (1.28, 1.61), 0.98 (0.85, 1.12) and 1.04 (0.95, 1.14) for ischaemic heart event (IHE), congestive heart failure (CHF), stroke and mortality, respectively. We observed a modest increase in likelihood for SA among RH compared to non-RH patients. Risks for IHE and CHF were higher for SA in RH compared to SA in non-RH patients; however, there were no differences in risk for stroke and mortality. © 2016 Asian Pacific Society of Respirology.

Aspirin and the Risk of Colorectal Cancer in Relation to the Expression of 15-Hydroxyprostaglandin Dehydrogenase (15-PGDH, HPGD)

PubMed Central

Fink, Stephen P.; Yamauchi, Mai; Nishihara, Reiko; Jung, Seungyoun; Kuchiba, Aya; Wu, Kana; Cho, Eunyoung; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji; Markowitz, Sanford D.; Chan, Andrew T.

2014-01-01

Aspirin use reduces the risk of colorectal neoplasia, at least in part, through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2)-related pathways. Hydroxyprostaglandin dehydrogenase 15-(NAD) (15-PGDH, HPGD) is downregulated in colorectal cancers and functions as a metabolic antagonist of PTGS2. We hypothesized that the effect of aspirin may be antagonized by low 15-PGDH expression in the normal colon. In the Nurses’ Health Study and the Health Professionals Follow-up Study, we collected data on aspirin use and other risk factors every two years and followed up participants for diagnoses of colorectal cancer. Duplication-method Cox proportional, multivariable-adjusted, cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for incident colorectal cancer according to 15-PGDH mRNA expression level measured in normal mucosa from colorectal cancer resections. Among 127,865 participants, we documented 270 colorectal cancer cases that developed during 3,166,880 person-years of follow-up and from which we could assess 15-PGDH expression. Compared with nonuse, regular aspirin use was associated with lower risk of colorectal cancer that developed within a background of colonic mucosa with high 15-PGDH expression (multivariable HR=0.49; 95% CI, 0.34–0.71), but not with low 15-PGDH expression (multivariable HR=0.90; 95% CI, 0.63–1.27) (P for heterogeneity=0.018). Regular aspirin use was associated with lower incidence of colorectal cancers arising in association with high 15-PGDH expression, but not with low 15-PGDH expression in normal colon mucosa. This suggests that 15-PGDH expression level in normal colon mucosa may serve as a biomarker which may predict stronger benefit from aspirin chemoprevention. PMID:24760190

Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients.

PubMed

Taubert, H; Würl, P; Greither, T; Kappler, M; Bache, M; Bartel, F; Kehlen, A; Lautenschläger, C; Harris, L C; Kaushal, D; Füssel, S; Meye, A; Böhnke, A; Schmidt, H; Holzhausen, H-J; Hauptmann, S

2007-11-01

Cancer stem cells can play an important role in tumorigenesis and tumor progression. However, it is still difficult to detect and isolate cancer stem cells. An alternative approach is to analyse stem cell-associated gene expression. We investigated the coexpression of three stem cell-associated genes, Hiwi, hTERT and survivin, by quantitative real-time-PCR in 104 primary soft-tissue sarcomas (STS). Multivariate Cox's proportional hazards regression analyses allowed correlating gene expression with overall survival for STS patients. Coexpression of all three stem cell-associated genes resulted in a significantly increased risk of tumor-related death. Importantly, tumors of patients with the poorest prognosis were of all four tumor stages, suggesting that their risk is based upon coexpression of stem cell-associated genes rather than on tumor stage.

Comparative effectiveness from a single-arm trial and real-world data: alectinib versus ceritinib.

PubMed

Davies, Jessica; Martinec, Michael; Delmar, Paul; Coudert, Mathieu; Bordogna, Walter; Golding, Sophie; Martina, Reynaldo; Crane, Gracy

2018-06-26

To compare the overall survival of anaplastic lymphoma kinase-positive non-small-cell lung cancer patients who received alectinib with those who received ceritinib. Two treatment arms (alectinib [n = 183] and ceritinib [n = 67]) were extracted from clinical trials and an electronic health record database, respectively. Propensity scores were applied to balance baseline characteristics. Kaplan-Meier and multivariate Cox regression were conducted. After propensity score adjustment, baseline characteristics were balanced. Alectinib had a prolonged median overall survival (alectinib = 24.3 months and ceritinib = 15.6 months) and lower risk of death (hazard ratio: 0.65; 95% CI: 0.48-0.88). Alectinib was associated with prolonged overall survival versus ceritinib, which is consistent with efficacy evidence from clinical trials.

ELASTIC NET FOR COX'S PROPORTIONAL HAZARDS MODEL WITH A SOLUTION PATH ALGORITHM.

PubMed

Wu, Yichao

2012-01-01

For least squares regression, Efron et al. (2004) proposed an efficient solution path algorithm, the least angle regression (LAR). They showed that a slight modification of the LAR leads to the whole LASSO solution path. Both the LAR and LASSO solution paths are piecewise linear. Recently Wu (2011) extended the LAR to generalized linear models and the quasi-likelihood method. In this work we extend the LAR further to handle Cox's proportional hazards model. The goal is to develop a solution path algorithm for the elastic net penalty (Zou and Hastie (2005)) in Cox's proportional hazards model. This goal is achieved in two steps. First we extend the LAR to optimizing the log partial likelihood plus a fixed small ridge term. Then we define a path modification, which leads to the solution path of the elastic net regularized log partial likelihood. Our solution path is exact and piecewise determined by ordinary differential equation systems.

Derivation of the linear-logistic model and Cox's proportional hazard model from a canonical system description.

PubMed

Voit, E O; Knapp, R G

1997-08-15

The linear-logistic regression model and Cox's proportional hazard model are widely used in epidemiology. Their successful application leaves no doubt that they are accurate reflections of observed disease processes and their associated risks or incidence rates. In spite of their prominence, it is not a priori evident why these models work. This article presents a derivation of the two models from the framework of canonical modeling. It begins with a general description of the dynamics between risk sources and disease development, formulates this description in the canonical representation of an S-system, and shows how the linear-logistic model and Cox's proportional hazard model follow naturally from this representation. The article interprets the model parameters in terms of epidemiological concepts as well as in terms of general systems theory and explains the assumptions and limitations generally accepted in the application of these epidemiological models.

Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

PubMed

Ishizuka, Mitsuru; Oyama, Yusuke; Abe, Akihito; Tago, Kazuma; Tanaka, Genki; Kubota, Keiichi

2014-08-01

To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma.

PubMed

Re, Massimo; Çeka, Artan; Rubini, Corrado; Ferrante, Luigi; Zizzi, Antonio; Gioacchini, Federico M; Tulli, Michele; Spazzafumo, Liana; Sellari-Franceschini, Stefano; Procopio, Antonio D; Olivieri, Fabiola

2015-09-01

Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival. Retrospective cohort study. Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Prognostic impact of intestinal wall thickening in hospitalized patients with heart failure.

PubMed

Ikeda, Yuki; Ishii, Shunsuke; Fujita, Teppei; Iida, Yuichiro; Kaida, Toyoji; Nabeta, Takeru; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Inomata, Takayuki; Ako, Junya

2017-03-01

Intestine-cardiovascular relationship has been increasingly recognized as a key factor in patients with heart disease. We aimed to identify the relationships among intestinal wall edema, cardiac function, and adverse clinical events in hospitalized heart failure (HF) patients. Abdominal computed tomographic images of 168 hospitalized HF patients were retrospectively investigated for identification of average colon wall thickness (CWT) from the ascending to sigmoid colon. Relationships between average CWT and echocardiographic parameters, blood sampling data, and primary outcomes including readmission for deteriorated HF and all-cause mortality were evaluated. Among the echocardiographic parameters, lower left ventricular diastolic function was correlated with higher average CWT. In multivariate analysis, higher logarithmic C-reactive protein level, lower estimated glomerular filtration rate, lower peripheral blood lymphocyte count, higher E/E' ratio, and extremely higher/lower defecation frequency were independently correlated with higher average CWT. Multivariate Cox-hazard analysis demonstrated that higher average CWT was independently related to higher incidence of primary outcomes. In hospitalized HF patients, increased CWT was associated with lower cardiac performance, and predicted poorer long-term clinical outcomes. Copyright © 2016. Published by Elsevier B.V.

Prospective analysis of body mass index, physical activity and colorectal cancer risk associated with β-catenin (CTNNB1) status

PubMed Central

Morikawa, Teppei; Kuchiba, Aya; Lochhead, Paul; Nishihara, Reiko; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Qian, Zhi Rong; Ng, Kimmie; Chan, Andrew T.; Meyerhardt, Jeffrey A.; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji

2013-01-01

Dysregulation of the WNT/β-catenin (CTNNB1) signaling pathway is implicated in colorectal carcinoma and metabolic diseases. Considering these roles and cancer prevention, we hypothesized that tumor CTNNB1 status might influence cellular sensitivity to obesity and physical activity. In clinical follow-up of 109,046 women in the Nurses' Health Study and 47,684 men in the Health Professionals Follow-up Study, there were 861 incident rectal and colon cancers with tissue immunohistochemistry data on nuclear CTNNB1 expression. Using this molecular pathological epidemiology database, we performed Cox proportional hazards regression analysis using data duplication method to assess differential associations of body mass index (BMI) or exercise activity with colorectal cancer risk according to tumor CTNNB1 status. Greater BMI was associated with a significantly higher risk of CTNNB1-negative cancer [multivariate hazard ratio (HR) =1.34; 95% confidence interval (CI), 1.18–1.53 for 5.0 kg/m2 increment; Ptrend=0.0001], but not with CTNNB1-positive cancer risk (multivariate HR =1.07; 95% CI, 0.92–1.25 for 5.0 kg/m2 increment; Ptrend=0.36; Pheterogeneity=0.027, between CTNNB1-negative and CTNNB1-positive cancer risks). Physical activity level was associated with a lower risk of CTNNB1-negative cancer (multivariate HR =0.93; 95% CI, 0.87–1.00 for 10 MET-hours/week increment; Ptrend=0.044), but not with CTNNB1-positive cancer risk (multivariate HR =0.98; 95% CI, 0.91–1.05 for 10 MET-hours/week increment; Ptrend=0.60). Our findings argue that obesity and physical inactivity are associated with a higher risk of CTNNB1-negative colorectal cancer, but not with CTNNB1-positive cancer risk. Further, they suggest that energy balance and metabolism status exerts its effect in a specific carcinogenesis pathway that is less likely dependent on WNT/CTNNB1 activation. PMID:23442321

The effects of building design on hazard of first service in Norwegian dairy cows.

PubMed

Martin, A D; Kielland, C; Nelson, S T; Østerås, O

2015-12-01

Reproductive inefficiency is one of the major production and economic constraints on modern dairy farms. The environment affects onset of ovarian activity in a cow postcalving and influences estrus behavior, which in turn affects a stockperson's ability to inseminate her at the correct time. This study used survival analysis to investigate effects of building design and animal factors on the postpartum hazard of first service (HFS) in freestall-housed Norwegian Red cows. The study was performed on 232 Norwegian dairy farms between 2004 and 2007. Data were obtained through on farm measurements and by accessing the Norwegian Dairy Herd Recording System. The final data set contained data on 38,436 calvings and 27,127 services. Univariate Cox proportional hazard analyses showed that herd size and milk yield were positively associated with HFS. Total free accessible area and free accessible area available per cow year were positively associated with the HFS, as was the number of freestalls available per cow. Cows housed on slatted floors had a lower HFS than those housed on solid floors. Conversely, cows housed on rubber floors had a higher HFS than cows on concrete floors. Dead-ending alleyways reduced the hazard of AI after calving. A multivariable Cox proportional hazards model, accounting for herd management by including a frailty term for herd, showed relationships between hazard of postpartum service and explanatory variables. Animals in herds with more than 50 cows had a higher HFS [hazard ratio (HR)=3.0] compared with those in smaller herds. The HFS was also higher (HR=4.3) if more than 8.8 m(2) of space was available per cow year compared with herds in which animals had less space. The HFS after calving increased with parity (parity 2 HR=0.5, parity ≥3 HR=1.7), and was reduced if a lactation began with dystocia (HR=0.82) or was a breed other than Norwegian Red (HR=0.2). The frailty term, herd, was large and highly significant indicating a significant proportion of the variation resides at herd level. The hazard of first insemination decreased with time for all predictive variables, except dystocia. This study shows that providing adequate environmental conditions for estrus behavior is imperative for reproductive efficiency and after herd management factors and time from calving have been accounted for. Thus, optimizing building design for reproductive efficiency is of significant importance when constructing new cattle housing. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease.

PubMed

Martinez-Aguilar, Esther; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, Sebastián; Rodríguez, Jose A; Fernández-Alonso, Leopoldo; Páramo, Jose A; Roncal, Carmen

2017-11-01

The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with higher risk of cardiovascular (CV) complications and death in different atherosclerotic diseases, recent epidemiologic studies have challenged its prognostic utility. The aim of this study was to test the predictive value of HDL-C as a risk factor for ischemic events or death in symptomatic PAD patients. Clinical and demographic parameters of 254 symptomatic PAD patients were recorded. Amputation, ischemic coronary disease, cerebrovascular disease, and all-cause mortality were recorded during a mean follow-up of 2.7 years. Multivariate analyses showed that disease severity (critical limb ischemia) was significantly reduced in patients with normal HDL-C levels compared with the group with low HDL-C levels (multivariate analysis odds ratio, 0.09; 95% confidence interval [CI], 0.03-0.24). A decreased risk for mortality (hazard ratio, 0.46; 95% CI, 0.21-0.99) and major adverse CV events (hazard ratio, 0.38; 95% CI, 0.16-0.86) was also found in patients with normal vs reduced levels of HDL-C in both Cox proportional hazards models and Kaplan-Meier estimates, after adjustment for confounding factors. Reduced HDL-C levels were significantly associated with higher risk for development of CV complications as well as with mortality in PAD patients. These findings highlight the usefulness of this simple test for early identification of PAD patients at high risk for development of major CV events. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence.

PubMed

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S; Price, Karen N; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

2016-07-20

To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. © 2016 by American Society of Clinical Oncology.

Fertility preservation in women with borderline ovarian tumors - how does it impact disease outcome? A cohort study.

PubMed

Helpman, Limor; Yaniv, Assaf; Beiner, Mario E; Aviel-Ronen, Sarit; Perri, Tamar; Ben-Baruch, Gilad; Hogen Ben-David, Liat; Jakobson-Setton, Ariella; Korach, Jacob

2017-11-01

Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility-sparing approach. A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981-2011). Data on surgical approach (fertility-sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow-up data were collected. Recurrence and survival were assessed using the Kaplan-Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model. 213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility-sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1-6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3-7.6; p < 0.001) were independently associated with recurrence on multivariate analysis. Eleven (5%) patients died of their disease. Fertility preservation was not associated with compromised survival. Borderline ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Predictors of liver-related death among people who inject drugs in Vancouver, Canada: a 15-year prospective cohort study

PubMed Central

Hayashi, Kanna; Milloy, Michael-John; Wood, Evan; Dong, Huiru; Montaner, Julio SG; Kerr, Thomas

2014-01-01

Introduction While HIV/AIDS remains an important cause of death among people who inject drugs (PWID), the potential mortality burden attributable to hepatitis C virus (HCV) infection among this population is of increasing concern. Therefore, we sought to identify trends in and predictors of liver-related mortality among PWID. Methods Data were derived from prospective cohorts of PWID in Vancouver, Canada, between 1996 and 2011. Cohort data were linked to the provincial vital statistics database to ascertain mortality rates and causes of death. Multivariate Cox proportional hazards regression was used to examine the relationship between HCV infection and time to liver-related death. A sub-analysis examined the effect of HIV/HCV co-infection. Results and discussion In total, 2,279 PWID participated in this study, with 1,921 (84.3%) having seroconverted to anti-HCV prior to baseline assessments and 124 (5.4%) during follow-up. The liver-related mortality rate was 2.1 (95% confidence interval [CI]: 1.5–3.0) deaths per 1,000 person-years and was stable over time. In multivariate analyses, HCV seropositivity was not significantly associated with liver-related mortality (adjusted relative hazard [ARH]: 0.45; 95% CI: 0.15–1.37), but HIV seropositivity was (ARH: 2.67; 95% CI: 1.27–5.63). In sub-analysis, HIV/HCV co-infection had a 2.53 (95% CI: 1.18–5.46) times hazard of liver-related death compared with HCV mono-infection. Conclusions In this study, HCV seropositivity did not predict liver-related mortality while HIV seropositivity did. The findings highlight the critical role of HIV mono- and co-infection rather than HCV infection in contributing to liver-related mortality among PWID in this setting. PMID:25391765

A 10-Year Retrospective Review of a Nonrandomized Cohort of 458 Patients Undergoing Radical Radiotherapy or Cystectomy in Yorkshire, UK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munro, Nicholas P., E-mail: nic@munron.plus.co; Sundaram, Subramnian K.; Weston, Philip

2010-05-01

Purpose: We have previously reported on the mortality, morbidity, and 5-year survival of 458 patients who underwent radical radiotherapy or surgery for invasive bladder cancer in Yorkshire from 1993 to 1996. We aim to present the 10-year outcomes of these patients and to reassess factors predicting survival. Methods and Materials: The Northern and Yorkshire Cancer Registry identified 458 patients whose cases were subjected to Kaplan-Meier all-cause survival analyses, and a retrospective casenote analysis was undertaken on 398 (87%) for univariate and multivariate Cox proportional hazards modeling. Additional proportional hazards regression modeling was used to assess the statistical significance of variablesmore » on overall survival. Results: The ratio of radiotherapy to cystectomy was 3:1. There was no significant difference in overall 10-year survival between those who underwent radiotherapy (22%) and radical cystectomy (24%). Univariate analyses suggested that female sex, performance status, hydronephrosis and clinical T stage, were associated with an inferior outcome at 10 years. Patient age, tumor grade, treatment delay, and caseload factors were not significant. Multivariate analysis models were created for 0-2 and 2-10 years after treatment. There were no significant differences in treatment for 0-2 years; however, after 2 years follow-up there was some evidence of increased survival for patients receiving surgery compared with radiotherapy (hazard ratio 0.66, 95% confidence interval: 0.44-1.01, p = 0.06). Conclusions: a 10-year minimum follow-up has rarely been reported after radical treatment for invasive bladder cancer. At 10 years, there was no statistical difference in all-cause survival between surgery and radiotherapy treatment modalities.« less

Is There a Dose-Response Relationship between Tea Consumption and All-Cause, CVD, and Cancer Mortality?

PubMed

Yan, Yi; Sui, Xuemei; Yao, Bin; Lavie, Carl J; Blair, Steven N

2017-01-01

A small change in tea consumption at population level could have large impact on public health. However, the health benefits of tea intake among Americans are inconclusive. To evaluate the association between tea consumption and all-causes, cardiovascular disease (CVD) and cancer mortality in the Aerobics Center Longitudinal study (ACLS). 11808 participants (20-82 years) initially free of CVD and cancers enrolled in the ACLS and were followed for mortality. Participants provided baseline self-report of tea consumption (cups/day). During a median follow-up of 16 years, 842 participants died. Of others, 250 died from CVD, and 345 died from cancer, respectively. A Cox proportional hazard model was used to produce hazard ratio (HR) and 95% confidence interval (CI). Compared with participants consuming no tea, tea drinkers had a survival advantage ( Log-2 = 10.2, df = 3, P = 0.017); however, the multivariate hazard ratios (HRs) of all-cause mortality for those drinking 1-7, 8-14, and >14 cups/week were 0.95 (95% CI, 0.81-1.12), 1.00 (95% CI, 0.82-1.22), and 0.98 (95% CI, 0.76-1.25), respectively (P for linear trend = 0.83). The multivariate HR were 1.16 (95% CI, 0.86-1.56), 1.22 (95% CI, 0.85-1.76), and 0.94 (95% CI, 0.56-1.54) for CVD mortality (P for linear trend = 0.47), and 0.97 (95% CI, 0.75-1.25), 0.85 (95% CI, 0.60-1.16), and 0.94 (95% CI, 0.64-1.38) for cancer mortality (P for trend = 0.62). There were week or null relationships between tea consumption and mortality due to all-cause, CVD disease or cancer were observed in ACLS.

Racial and ethnic differences in patient navigation: Results from the Patient Navigation Research Program.

PubMed

Ko, Naomi Y; Snyder, Frederick R; Raich, Peter C; Paskett, Electra D; Dudley, Donald J; Lee, Ji-Hyun; Levine, Paul H; Freund, Karen M

2016-09-01

Patient navigation was developed to address barriers to timely care and reduce cancer disparities. The current study explored navigation and racial and ethnic differences in time to the diagnostic resolution of a cancer screening abnormality. The authors conducted an analysis of the multisite Patient Navigation Research Program. Participants with an abnormal cancer screening test were allocated to either navigation or control. The unadjusted median time to resolution was calculated for each racial and ethnic group by navigation and control. Multivariable Cox proportional hazards models were fit, adjusting for sex, age, cancer abnormality type, and health insurance and stratifying by center of care. Among a sample of 7514 participants, 29% were non-Hispanic white, 43% were Hispanic, and 28% were black. In the control group, black individuals were found to have a longer median time to diagnostic resolution (108 days) compared with non-Hispanic white individuals (65 days) or Hispanic individuals (68 days) (P<.0001). In the navigated groups, black individuals had a reduction in the median time to diagnostic resolution (97 days) (P<.0001). In the multivariable models, among controls, black race was found to be associated with an increased delay to diagnostic resolution (hazard ratio, 0.77; 95% confidence interval, 0.69-0.84) compared with non-Hispanic white individuals, which was reduced in the navigated arm (hazard ratio, 0.85; 95% confidence interval, 0.77-0.94). Patient navigation appears to have the greatest impact among black patients, who had the greatest delays in care. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2715-2722. © 2016 American Cancer Society. © 2016 American Cancer Society.

Exercise Capacity and the Obesity Paradox in Heart Failure: The FIT (Henry Ford Exercise Testing) Project.

PubMed

McAuley, Paul A; Keteyian, Steven J; Brawner, Clinton A; Dardari, Zeina A; Al Rifai, Mahmoud; Ehrman, Jonathan K; Al-Mallah, Mouaz H; Whelton, Seamus P; Blaha, Michael J

2018-05-03

To assess the influence of exercise capacity and body mass index (BMI) on 10-year mortality in patients with heart failure (HF) and to synthesize these results with those of previous studies. This large biracial sample included 774 men and women (mean age, 60±13 years; 372 [48%] black) with a baseline diagnosis of HF from the Henry Ford Exercise Testing (FIT) Project. All patients completed a symptom-limited maximal treadmill stress test from January 1, 1991, through May 31, 2009. Patients were grouped by World Health Organization BMI categories for Kaplan-Meier survival analyses and stratified by exercise capacity (<4 and ≥4 metabolic equivalents [METs] of task). Associations of BMI and exercise capacity with all-cause mortality were assessed using multivariable-adjusted Cox proportional hazards models. During a mean follow-up of 10.1±4.6 years, 380 patients (49%) died. Kaplan-Meier survival plots revealed a significant positive association between BMI category and survival for exercise capacity less than 4 METs (log-rank, P=.05), but not greater than or equal to 4 METs (P=.76). In the multivariable-adjusted models, exercise capacity (per 1 MET) was inversely associated, but BMI was not associated, with all-cause mortality (hazard ratio, 0.89; 95% CI, 0.85-0.94; P<.001 and hazard ratio, 0.99; 95% CI, 0.97-1.01; P=.16, respectively). Maximal exercise capacity modified the relationship between BMI and long-term survival in patients with HF, upholding the presence of an exercise capacity-obesity paradox dichotomy as observed over the short-term in previous studies. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Elevated serum creatinine and low albumin are associated with poor outcomes in patients with liposarcoma.

PubMed

Panotopoulos, Joannis; Posch, Florian; Funovics, Philipp T; Willegger, Madeleine; Scharrer, Anke; Lamm, Wolfgang; Brodowicz, Thomas; Windhager, Reinhard; Ay, Cihan

2016-03-01

Low serum albumin levels and impaired kidney function have been associated with decreased survival in patients with a variety of cancer types. In a retrospective cohort study, we analyzed 84 patients with liposarcoma treated at from May 1994 to October 2011. Uni- and multivariable Cox proportional hazard models and competing risk analyses were performed to evaluate the association between putative biomarkers with disease-specific and overall survival. The median age of the study population was 51.7 (range 19.6-83.8) years. In multivariable analysis adjusted for AJCC tumor stage, serum creatinine was highly associated with disease-specific survival (Subdistribution Hazard ratio (SHR) per 1 mg/dl increase = 2.94; 95%CI 1.39-6.23; p = 0.005). High albumin was associated with improved overall and disease-specific survival (Hazard Ratio (HR) per 10 units increase = 0.50; 95%CI 0.26-0.95; p = 0.033 and SHR = 0.64; 95%CI 0.42-1.00; p = 0.049). The serum albumin-creatinine-ratio emerged to be associated with both overall and disease-specific survival after adjusting for AJCC tumor stage (HR = 0.95; 95%CI 0.92-0.99; p = 0.011 and SHR = 0.96; 95%CI 0.93-0.99; p = 0.08). Our study provides evidence for a tumor-stage-independent association between higher creatinine and lower albumin with worse disease-specific survival. Low albumin and a high albumin-creatinine-ratio independently predict poor overall survival. Our work identified novel prognostic biomarkers for prognosis of patients with liposarcoma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome.

PubMed

Mathias, Andrew; Moss, Arthur J; Lopes, Coeli M; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Robinson, Jennifer L; Locati, Emanuela H; Ackerman, Michael J; Benhorin, Jesaia; Kaufman, Elizabeth S; Platonov, Pyotr G; Qi, Ming; Shimizu, Wataru; Towbin, Jeffrey A; Michael Vincent, G; Wilde, Arthur A M; Zhang, Li; Goldenberg, Ilan

2013-05-01

Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc. The study population comprised 1206 patients with LQTS with 95 different mutations and ≥ 5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype. Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20 ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002). Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype. Copyright © 2013. Published by Elsevier Inc.

Serial changes and prognostic implications of CT findings in combined pulmonary fibrosis and emphysema: comparison with fibrotic idiopathic interstitial pneumonias alone.

PubMed

Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo

2017-05-01

Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.

Short sleep duration as an independent predictor of cardiovascular events in Japanese patients with hypertension.

PubMed

Eguchi, Kazuo; Pickering, Thomas G; Schwartz, Joseph E; Hoshide, Satoshi; Ishikawa, Joji; Ishikawa, Shizukiyo; Shimada, Kazuyuki; Kario, Kazuomi

2008-11-10

It is not known whether short duration of sleep is a predictor of future cardiovascular events in patients with hypertension. To test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD), we performed ambulatory blood pressure (BP) monitoring in 1255 subjects with hypertension (mean [SD] age, 70.4 [9.9] years) and followed them for a mean period of 50 (23) months. Short sleep duration was defined as less than 7.5 hours (20th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio and 95% confidence interval (CI) for short sleep duration. A riser pattern was defined when mean nighttime systolic BP exceeded daytime systolic BP. The end point was a cardiovascular event: stroke, fatal or nonfatal myocardial infarction (MI), and sudden cardiac death. In multivariable analyses, short duration of sleep (<7.5 hours) was associated with incident CVD (hazard ratio [HR], 1.68; 95% CI, 1.06-2.66; P = .03). A synergistic interaction was observed between short sleep duration and the riser pattern (P = .09). When subjects were classified according to their sleep time and a riser vs nonriser pattern, the group with shorter sleep duration plus the riser pattern had a substantially and significantly higher incidence of CVD than the group with predominant normal sleep duration plus the nonriser pattern (HR, 4.43; 95% CI, 2.09-9.39; P < .001), independent of covariates. Short duration of sleep is associated with incident CVD risk and the combination of the riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of patients with hypertension.

Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study.

PubMed

Velásquez, Gustavo E; Cegielski, J Peter; Murray, Megan B; Yagui, Martin J A; Asencios, Luis L; Bayona, Jaime N; Bonilla, César A; Jave, Hector O; Yale, Gloria; Suárez, Carmen Z; Sanchez, Eduardo; Rojas, Christian; Atwood, Sidney S; Contreras, Carmen C; Santa Cruz, Janeth; Shin, Sonya S

2016-02-01

Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. Of 1701 participants treated for tuberculosis, 136 (8.0%) died during tuberculosis treatment. HIV-positive patients constituted 11.0% of the cohort and contributed to 34.6% of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9%, P < 0.001) and less likely to be cured (28.3 vs. 39.4%, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95% confidence interval [CI], 3.96-9.27), unemployment (HR = 2.24; 95% CI, 1.55-3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95% CI, 1.10-3.31) were significantly associated with a higher hazard of death. We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality.

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

PubMed Central

Giobbie-Hurder, Anita; Coates, Alan S.; Price, Karen N.; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D.; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F.; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

2016-01-01

Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor–positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. PMID:27217455

Marginal Structural Models for Case-Cohort Study Designs to Estimate the Association of Antiretroviral Therapy Initiation With Incident AIDS or Death

PubMed Central

Cole, Stephen R.; Hudgens, Michael G.; Tien, Phyllis C.; Anastos, Kathryn; Kingsley, Lawrence; Chmiel, Joan S.; Jacobson, Lisa P.

2012-01-01

To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time-varying confounding in a cost-efficient manner, the authors combined a case-cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding. PMID:22302074

Pigmentation Traits, Sun Exposure, and Risk of Incident Vitiligo in Women.

PubMed

Dunlap, Rachel; Wu, Shaowei; Wilmer, Erin; Cho, Eunyoung; Li, Wen-Qing; Lajevardi, Newsha; Qureshi, Abrar

2017-06-01

Vitiligo is the most common cutaneous depigmentation disorder worldwide, yet little is known about specific risk factors for disease development. Using data from the Nurses' Health Study, a prospective cohort study of 51,337 white women, we examined the associations between (i) pigmentary traits and (ii) reactions to sun exposure and risk of incident vitiligo. Nurses' Health Study participants responded to a question about clinician-diagnosed vitiligo and year of diagnosis (2001 or before, 2002-2005, 2006-2009, 2010-2011, or 2012+). We used Cox proportional hazards regression models to estimate the multivariate-adjusted hazard ratios and 95% confidence intervals of incident vitiligo associated with exposures variables, adjusting for potential confounders. We documented 271 cases of incident vitiligo over 835,594 person-years. Vitiligo risk was higher in women who had at least one mole larger than 3 mm in diameter on their left arms (hazard ratio = 1.37, 95% confidence interval = 1.02-1.83). Additionally, vitiligo risk was higher among women with better tanning ability (hazard ratio = 2.59, 95% confidence interval = 1.21-5.54) and in women who experienced at least one blistering sunburn (hazard ratio = 2.17, 95% confidence interval = 1.15-4.10). In this study, upper extremity moles, a higher ability to achieve a tan, and history of a blistering sunburn were associated with a higher risk of developing vitiligo in a population of white women. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Reporting and methodological quality of survival analysis in articles published in Chinese oncology journals.

PubMed

Zhu, Xiaoyan; Zhou, Xiaobin; Zhang, Yuan; Sun, Xiao; Liu, Haihua; Zhang, Yingying

2017-12-01

Survival analysis methods have gained widespread use in the filed of oncology. For achievement of reliable results, the methodological process and report quality is crucial. This review provides the first examination of methodological characteristics and reporting quality of survival analysis in articles published in leading Chinese oncology journals.To examine methodological and reporting quality of survival analysis, to identify some common deficiencies, to desirable precautions in the analysis, and relate advice for authors, readers, and editors.A total of 242 survival analysis articles were included to be evaluated from 1492 articles published in 4 leading Chinese oncology journals in 2013. Articles were evaluated according to 16 established items for proper use and reporting of survival analysis.The application rates of Kaplan-Meier, life table, log-rank test, Breslow test, and Cox proportional hazards model (Cox model) were 91.74%, 3.72%, 78.51%, 0.41%, and 46.28%, respectively, no article used the parametric method for survival analysis. Multivariate Cox model was conducted in 112 articles (46.28%). Follow-up rates were mentioned in 155 articles (64.05%), of which 4 articles were under 80% and the lowest was 75.25%, 55 articles were100%. The report rates of all types of survival endpoint were lower than 10%. Eleven of 100 articles which reported a loss to follow-up had stated how to treat it in the analysis. One hundred thirty articles (53.72%) did not perform multivariate analysis. One hundred thirty-nine articles (57.44%) did not define the survival time. Violations and omissions of methodological guidelines included no mention of pertinent checks for proportional hazard assumption; no report of testing for interactions and collinearity between independent variables; no report of calculation method of sample size. Thirty-six articles (32.74%) reported the methods of independent variable selection. The above defects could make potentially inaccurate, misleading of the reported results, or difficult to interpret.There are gaps in the conduct and reporting of survival analysis in studies published in Chinese oncology journals, severe deficiencies were noted. More endorsement by journals of the report guideline for survival analysis may improve articles quality, and the dissemination of reliable evidence to oncology clinicians. We recommend authors, readers, reviewers, and editors to consider survival analysis more carefully and cooperate more closely with statisticians and epidemiologists. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Weight Cycling and Cancer Incidence in a Large Prospective US Cohort

PubMed Central

Stevens, Victoria L.; Jacobs, Eric J.; Patel, Alpa V.; Sun, Juzhong; McCullough, Marjorie L.; Campbell, Peter T.; Gapstur, Susan M.

2015-01-01

Weight cycling, which consists of repeated cycles of intentional weight loss and regain, is common among individuals who try to lose weight. Some evidence suggests that weight cycling may affect biological processes that could contribute to carcinogenesis, but whether it is associated with cancer risk is unclear. Using 62,792 men and 69,520 women enrolled in the Cancer Prevention Study II Nutrition Cohort in 1992, we examined the association between weight cycling and cancer incidence. Weight cycles were defined by using baseline questions that asked the number of times ≥10 pounds (4.54 kg) was purposely lost and later regained. Multivariable-adjusted hazard ratios and 95% confidence intervals for all cancer and 15 individual cancers were estimated by using Cox proportional hazards regression. During up to 17 years of follow-up, 15,333 men and 9,984 women developed cancer. Weight cycling was not associated with overall risk of cancer in men (hazard ratio = 0.96, 95% confidence interval: 0.83, 1.11 for ≥20 cycles vs. no weight cycles) or women (hazard ratio = 0.96, 95% confidence interval: 0.86, 1.08) in models that adjusted for body mass index and other covariates. Weight cycling was also not associated with any individual cancer investigated. These results suggest that weight cycling, independent of body weight, is unlikely to influence subsequent cancer risk. PMID:26209523

COX-2/EGFR expression and survival among women with adenocarcinoma of the lung

PubMed Central

Van Dyke, Alison L.; Cote, Michele L.; Prysak, Geoffrey M.; Claeys, Gina B.; Wenzlaff, Angie S.; Murphy, Valerie C.; Lonardo, Fulvio; Schwartz, Ann G.

2008-01-01

Previous studies suggest that cyclooxygenase-2 (COX-2) expression may predict survival among patients with non-small cell lung cancer. COX-2 may interact with epidermal growth factor receptor (EGFR), suggesting that combined COX-2/EGFR expression may provide predictive value. The extent to which their independent or combined expression is associated with prognosis in women with adenocarcinoma of the lung is unknown. In the present study, we examined relationships between COX-2 expression (n = 238), EGFR expression (n = 158) and dual COX-2/EGFR expression (n = 157) and survival among women with adenocarcinoma of the lung. Overall survival was estimated by constructing Cox proportional hazards models adjusting for other significant variables and stratifying by stage at diagnosis and race. Clinical or demographic parameters were not associated with either COX-2 or EGFR expression. Patients with COX-2-positive tumors tended to have poorer prognosis than did patients with COX-2-negative tumors [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.01–2.78]. African-Americans with COX-2-positive tumors had a statistically non-significant higher risk of death than African-Americans with COX-2-negative tumors (HR 5.58, 95% CI 0.64–48.37). No association between COX-2 expression and survival was observed among Caucasians (HR 1.29, 95% CI 0.72–2.30). EGFR expression was associated with a 44% reduction in the risk of death (HR 0.56, 95% CI 0.32–0.98). COX-2−/EGFR+ tumor expression, but not COX-2+/EGFR+ tumor expression, was associated with survival when compared with other combined expression results. In conclusion, COX-2 and EGFR expression, but not combined COX-2+/EGFR+ expression, independently predict survival of women with adenocarcinoma of the lung. PMID:18453539

The relationship between the effect of pravastatin and risk factors for coronary heart disease in Japanese patients with hypercholesterolemia.

PubMed

Ishikawa, Toshitsugu; Mizuno, Kyoichi; Nakaya, Noriaki; Ohashi, Yasuo; Tajima, Naoko; Kushiro, Toshio; Teramoto, Tamio; Uchiyama, Shinichiro; Nakamura, Haruo

2008-10-01

Several epidemiologic studies in Japan have shown the risk factors for coronary heart disease (CHD) in the general population. The present analysis determined the risk factors for CHD in the MEGA Study, a large primary prevention trial with pravastatin in Japanese with hypercholesterolemia. The relationship between each baseline characteristic and the risk of CHD for the 5-year study period were evaluated using the Cox proportional hazard model. The multivariable predictors of CHD were sex, age, high-density lipoprotein-cholesterol (HDL-C), diabetes mellitus (DM), hypertension (HT), and history of smoking. Serum total and low-density lipoprotein-cholesterol were not independent risk factors for CHD in the current analysis. In addition, the effect of pravastatin was evaluated by subgroups in each risk factor using the interaction in a Cox model. Diet plus pravastatin treatment reduced CHD risk by 14-43% compared with diet alone, regardless of the presence or absence of risk factors. The risk factors for CHD were sex, age, DM, HT, smoking, and low HDL-C in the MEGA Study. The pravastatin treatment was effective for reducing the risk of CHD, regardless of the presence of risk factors.

The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study.

PubMed

Kawashima, Atsunari; Nakai, Yasutomo; Nakayama, Masashi; Ujike, Takeshi; Tanigawa, Go; Ono, Yutaka; Kamoto, Akihito; Takada, Tsuyosi; Yamaguchi, Yuichiro; Takayama, Hitoshi; Nishimura, Kazuo; Nonomura, Norio; Tsujimura, Akira

2012-10-01

To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required.

A prospective study of periodontal disease and pancreatic cancer in US male health professionals.

PubMed

Michaud, Dominique S; Joshipura, Kaumudi; Giovannucci, Edward; Fuchs, Charles S

2007-01-17

Two previous cohort studies reported positive associations between tooth loss or periodontitis and pancreatic cancer risk. Data on periodontal disease were obtained at baseline and every other year thereafter in a cohort of 51,529 male health professionals aged 40-75 years. A total of 216 patients were diagnosed with incident pancreatic cancer during 16 years of follow-up. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models controlling for potential confounders, including detailed smoking history. All statistical tests were two-sided. Compared with no periodontal disease, history of periodontal disease was associated with increased pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26; P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline number of natural teeth and cumulative tooth loss during follow-up were not strongly associated with pancreatic cancer. The association between periodontal disease and increased risk of pancreatic cancer may occur through plausible biologic mechanisms, but confirmation of this association is necessary.

Patients started on hemodialysis with tunneled dialysis catheter have similar survival after arteriovenous fistula and arteriovenous graft creation.

PubMed

Yuo, Theodore H; Chaer, Rabih A; Dillavou, Ellen D; Leers, Steven A; Makaroun, Michel S

2015-12-01

Current guidelines suggest that arteriovenous fistula (AVF) is associated with survival advantage over arteriovenous graft (AVG). However, AVFs often require months to become functional, increasing tunneled dialysis catheter (TDC) use, which can erode the benefit of an AVF. We sought to compare survival in patients with end-stage renal disease after creation of an AVF or AVG in patients starting hemodialysis (HD) with a TDC and to identify patient populations that may benefit from preferential use of AVG over AVF. Using U.S. Renal Data System databases, we identified incident HD patients in 2005 through 2008 and observed them through 2008. Initial access type and clinical variables including albumin levels were assessed using U.S. Renal Data System data collection forms. Attempts at AVF and AVG creation in patients who started HD through a TDC were identified by Current Procedural Terminology codes. We accounted for the effect of changes in access type by truncating follow-up when an additional AVF or AVG was performed. Survival curves were then constructed, and log-rank tests were used for pairwise survival comparisons, stratified by age. Multivariate analysis was performed with Cox proportional hazards regressions; variables were chosen using stepwise elimination. An interaction of access type and albumin level was detected, and Cox models using differing thresholds for albumin level were constructed. The primary outcome was survival. Among the 138,245 patients who started with a TDC and had complete records amenable for analysis, 22.8% underwent AVF creation (mean age ± standard deviation, 68.9 ± 12.5 years; 27.8% mortality at 1 year) and 7.6% underwent AVG placement (70.2 ± 12.0 years; 28.2% mortality) within 3 months of HD initiation; 69.6% remained with a TDC (63.2 ± 15.4 years; 33.8% mortality). In adjusted Cox proportional hazards regression, AVF creation is equivalent to AVG placement in terms of survival (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.93-1.02; P = .349). AVG placement is superior to continued TDC use (HR, 1.54; 95% CI, 1.48-1.61; P < .001). In patients older than 80 years with albumin levels >4.0 g/dL, AVF creation is associated with higher mortality hazard compared with AVG creation (HR, 1.22; 95% CI, 1.04-1.43; P = .013). For patients who start HD through a TDC, placement of an AVF and AVG is associated with similar mortality hazard. Further study is necessary to determine the ideal access for patients in whom the survival advantage of an AVF over an AVG is uncertain. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Validation of Methods to Control for Immortal Time Bias in a Pharmacoepidemiologic Analysis of Renin–Angiotensin System Inhibitors in Type 2 Diabetes

PubMed Central

Yang, Xilin; Kong, Alice PS; Luk, Andrea OY; Ozaki, Risa; Ko, Gary TC; Ma, Ronald CW; Chan, Juliana CN; So, Wing Yee

2014-01-01

Background Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin–angiotensin system (RAS) inhibitors as the reference cardioprotective drug. Methods We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. Results During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68–1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. Conclusions In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes. PMID:24747198

Allopurinol and Cardiovascular Outcomes in Adults With Hypertension.

PubMed

MacIsaac, Rachael L; Salatzki, Janek; Higgins, Peter; Walters, Matthew R; Padmanabhan, Sandosh; Dominiczak, Anna F; Touyz, Rhian M; Dawson, Jesse

2016-03-01

Allopurinol lowers blood pressure in adolescents and has other vasoprotective effects. Whether similar benefits occur in older individuals remains unclear. We hypothesized that allopurinol is associated with improved cardiovascular outcomes in older adults with hypertension. Data from the United Kingdom Clinical Research Practice Datalink were used. Multivariate Cox-proportional hazard models were applied to estimate hazard ratios for stroke and cardiac events (defined as myocardial infarction or acute coronary syndrome) associated with allopurinol use over a 10-year period in adults aged >65 years with hypertension. A propensity-matched design was used to reduce potential for confounding. Allopurinol exposure was a time-dependent variable and was defined as any exposure and then as high (≥300 mg daily) or low-dose exposure. A total of 2032 allopurinol-exposed patients and 2032 matched nonexposed patients were studied. Allopurinol use was associated with a significantly lower risk of both stroke (hazard ratio, 0.50; 95% confidence interval, 0.32-0.80) and cardiac events (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87) than nonexposed control patients. In exposed patients, high-dose treatment with allopurinol (n=1052) was associated with a significantly lower risk of both stroke (hazard ratio, 0.58; 95% confidence interval, 0.36-0.94) and cardiac events (hazard ratio, 0.65; 95% confidence interval, 0.46-0.93) than low-dose treatment (n=980). Allopurinol use is associated with lower rates of stroke and cardiac events in older adults with hypertension, particularly at higher doses. Prospective clinical trials are needed to evaluate whether allopurinol improves cardiovascular outcomes in adults with hypertension. © 2016 American Heart Association, Inc.

Clinical impact of altered T-cell homeostasis in treated HIV patients enrolled in a large observational cohort.

PubMed

Ndumbi, Patricia; Gillis, Jennifer; Raboud, Janet M; Cooper, Curtis; Hogg, Robert S; Montaner, Julio S G; Burchell, Ann N; Loutfy, Mona R; Machouf, Nima; Klein, Marina B; Tsoukas, Chris M

2013-11-28

We investigated the probability of transitioning in or out of the CD3⁺ T-cell homeostatic range during antiretroviral therapy, and we assessed the clinical impact of lost T-cell homeostasis (TCH) on AIDS-defining illnesses (ADIs) or death. Within the Canadian Observational Cohort (CANOC), we studied 4463 antiretroviral therapy (ART)-naive HIV-positive patients initiating combination ART (cART) between 2000 and 2010. CD3⁺ trajectories were estimated using a four state Markov model. CD3⁺ T-cel percentage states were classified as follows: very low (<50%), low (50-64%), normal (65-85%), and high (>85%). Covariates associated with transitioning between states were examined. The association between CD3⁺ T-cell percentage states and time to ADI/death from cART initiation was determined using Cox proportional hazards models. A total of 4463 patients were followed for a median of 3 years. Two thousand, five hundred and eight (56%) patients never transitioned from their baseline CD3⁺ T-cell percentage state; 85% of these had normal TCH. In multivariable analysis, individuals with time-updated low CD4⁺ cell count, time-updated detectable viral load, older age, and hepatitis C virus (HCV) coinfection were less likely to maintain TCH. In the multivariable proportional hazards model, both very low and high CD3⁺ T-cell percentages were associated with increased risk of ADI/death [adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27-2.89) and hazard ratio=1.49 (95% CI: 1.13-1.96), respectively]. Patients with very low or high CD3⁺ T-cell percentages are at risk for ADIs/death. To our knowledge, this is the first study linking altered TCH and morbidity/mortality in cART-treated HIV-positive patients.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

PubMed

Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

2012-12-01

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma

PubMed Central

Yeh, Hsin-Chih; Jan, Hau-Chern; Wu, Wen-Jeng; Li, Ching-Chia; Li, Wei-Ming; Ke, Hung-Lung; Huang, Shu-Pin; Liu, Chia-Chu; Lee, Yung-Chin; Yang, Sheau-Fang; Liang, Peir-In; Huang, Chun-Nung

2015-01-01

Objectives To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma. Methods In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated. Results Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P < 0.001 and P = 0.001, respectively) than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis. Conclusion Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract urothelial carcinoma. PMID:26469704

APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults.

PubMed

Gutiérrez, Orlando M; Irvin, Marguerite R; Chaudhary, Ninad S; Cushman, Mary; Zakai, Neil A; David, Victor A; Limou, Sophie; Pamir, Nathalie; Reiner, Alex P; Naik, Rakhi P; Sale, Michele M; Safford, Monika M; Hyacinth, Hyacinth I; Judd, Suzanne E; Kopp, Jeffrey B; Winkler, Cheryl A

2018-06-01

APOL1 renal risk variants are strongly associated with chronic kidney disease in Black adults, but reported associations with cardiovascular disease (CVD) have been conflicting. We examined associations of APOL1 with incident coronary heart disease (n=323), ischemic stroke (n=331), and the composite CVD outcome (n=500) in 10 605 Black participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Primary analyses compared individuals with APOL1 high-risk genotypes to APOL1 low-risk genotypes in Cox proportional hazards models adjusted for CVD risk factors and African ancestry. APOL1 high-risk participants were younger and more likely to have albuminuria at baseline than APOL1 low-risk participants. The risk of incident stroke, coronary heart disease, or composite CVD end point did not significantly differ by APOL1 genotype status in multivariable models. The association of APOL1 genotype with incident composite CVD differed by diabetes mellitus status ( P interaction =0.004). In those without diabetes mellitus, APOL1 high-risk genotypes associated with greater risk of incident composite CVD (hazard ratio, 1.67; 95% confidence interval, 1.12-2.47) compared with those with APOL1 low-risk genotypes in multivariable adjusted models. This latter association was driven by ischemic strokes (hazard ratio, 2.32; 95% confidence interval, 1.33-4.07), in particular, those related to small vessel disease (hazard ratio, 5.10; 95% confidence interval, 1.55-16.56). There was no statistically significant association of APOL1 genotypes with incident CVD in subjects with diabetes mellitus. The APOL1 high-risk genotype was associated with higher stroke risk in individuals without but not those with chronic kidney disease in fully adjusted models. APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus. © 2018 American Heart Association, Inc.

Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans.

PubMed

Kovesdy, Csaba P; Norris, Keith C; Boulware, L Ebony; Lu, Jun L; Ma, Jennie Z; Streja, Elani; Molnar, Miklos Z; Kalantar-Zadeh, Kamyar

2015-10-20

In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care. We compared all-cause mortality, incident coronary heart disease, and incident ischemic stroke using multivariable-adjusted Cox models in a nationwide cohort of 547 441 black and 2 525 525 white patients with baseline estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² receiving care from the US Veterans Health Administration. In parallel analyses, we compared outcomes in black versus white individuals in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. After multivariable adjustments in veterans, black race was associated with 24% lower all-cause mortality (adjusted hazard ratio, 0.76; 95% confidence interval, 0.75-0.77; P<0.001) and 37% lower incidence of coronary heart disease (adjusted hazard ratio, 0.63; 95% confidence interval, 0.62-0.65; P<0.001) but a similar incidence of ischemic stroke (adjusted hazard ratio, 0.99; 95% confidence interval, 0.97-1.01; P=0.3). Black race was associated with a 42% higher adjusted mortality among individuals with estimated glomerular filtration rate ≥ 60 mL·min⁻¹·1.73 m⁻² in NHANES (adjusted hazard ratio, 1.42; 95% confidence interval, 1.09-1.87). Black veterans with normal estimated glomerular filtration rate and equal access to healthcare have lower all-cause mortality and incidence of coronary heart disease and a similar incidence of ischemic stroke. These associations are in contrast to the higher mortality experienced by black individuals in the general US population. © 2015 American Heart Association, Inc.

Inverse Relationship of Blood Pressure to Long-Term Outcomes and Benefit of Cardiac Resynchronization Therapy in Patients With Mild Heart Failure: A Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Long-Term Follow-Up Substudy.

PubMed

Biton, Yitschak; Moss, Arthur J; Kutyifa, Valentina; Mathias, Andrew; Sherazi, Saadia; Zareba, Wojciech; McNitt, Scott; Polonsky, Bronislava; Barsheshet, Alon; Brown, Mary W; Goldenberg, Ilan

2015-09-01

Previous studies have shown that low blood pressure is associated with increased mortality and heart failure (HF) in patients with left ventricular dysfunction. Cardiac resynchronization therapy (CRT) was shown to increase systolic blood pressure (SBP). Therefore, we hypothesized that treatment with CRT would provide incremental benefit in patients with lower SBP values. The independent contribution of SBP to outcome was analyzed in 1267 patients with left bundle brunch block enrolled in Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). SBP was assessed as continuous measures and further categorized into approximate quintiles. The risk of long-term HF or death and CRT with defibrillator versus implantable cardioverter defibrillator benefit was assessed in multivariate Cox proportional hazards regression models. Multivariate analysis showed that in the implantable cardioverter defibrillator arm, each 10-mm Hg decrement of SBP was independently associated with a significant 21% (P<0.001) increased risk for HF or death, and patients with lower quintile SBP (<110 mm Hg) experienced a corresponding >2-fold risk-increase. CRT with defibrillator provided the greatest HF or mortality risk reduction in patients with SBP<110 mm Hg hazard ratio of 0.34, P<0.001, when compared with hazard ratio of 0.52, P<0.001, in those with 110>SBP≥136 mm Hg and hazard ratio of 0.94, P=0.808, with SBP>136 mm Hg (P for trend=0.001). In patients with mild HF, prolonged QRS, and left bundle brunch block, low SBP is related to higher risk of mortality or HF with implantable cardioverter defibrillator therapy alone. Treatment with CRT is associated with incremental clinical benefits in patients with lower baseline SBP values. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271. © 2015 American Heart Association, Inc.

Physical activity level and risk of death: the severance cohort study.

PubMed

Mok, Yejin; Won, Soyoung; Kimm, Heejin; Nam, Chungmo; Ohrr, Heechoul; Jee, Sun Ha

2012-01-01

Physical activity decreases deaths from cardiovascular disease and other causes; however, it is unclear whether physical activity is associated with cancer incidence and death in Asian populations. Data from 59 636 Koreans aged 30 to 93 years were collected using a questionnaire and medical examination at the Severance Hospital Health Promotion Center between 1994 and 2004. Study participants were followed for a mean duration of 10.3 years. In the exercising group, the multivariate Cox proportional hazards model showed a lower risk of cancer death (hazard ratio [HR] = 0.72, 95% CI = 0.62-0.85) in men but not in women. Those who exercised, as compared with those who did not, had lower risks of all-cause death (men: HR = 0.68, 95% CI = 0.60-0.76; women: HR = 0.65, 95% CI = 0.53-0.79) and noncancer death (men: 0.63, 0.53-0.75; women: 0.52, 0.39-0.69). Physical activity was inversely associated with risk of noncancer death among men and women. Physical activity was associated with lower risks of cancer death and noncancer death.

AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer.

PubMed

Al-Khafaji, Ahmed S K; Marcus, Michael W; Davies, Michael P A; Risk, Janet M; Shaw, Richard J; Field, John K; Liloglou, Triantafillos

2017-06-01

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases ( AURKA , AURKB and AURKC ), cytoskeleton-associated protein 5 ( CKAP5 ), discs large-associated protein 5 ( DLGAP5 ), kinesin-like protein 11 ( KIF11 ), microtubule nucleation factor ( TPX2 ), monopolar spindle 1 kinase ( TTK ), and β-tubulins ( TUBB ) and ( TUBB3 ) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC , all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

PubMed Central

Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

2017-01-01

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

PubMed

Peng, Li; Yuan, Xiao-Qing; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui; Li, Guan-Cheng

2017-01-03

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

Prolonged methylprednisolone therapy after the pulse treatment for patients with moderate-to-severe paraquat poisoning: A retrospective analysis.

PubMed

Gao, Jie; Feng, ShunYi; Wang, Jian; Yang, SiYuan; Li, Yong

2017-06-01

This retrospective study aims to evaluate the effect of prolonged methylprednisolone (MP) therapy on the mortality of patients with moderate-to-severe paraquat (PQ) poisoning after the pulse treatment.We performed a retrospective analysis of patients with acute moderate-to-severe PQ poisoning that were admitted to the emergency department from May 2012 to August 2016. Out of 138 patients, 60 were treated with pulse treatment (15 mg kg day MP for 3 days) and 78 were treated with prolonged MP therapy after pulse treatment (15 mg kg day MP for 3 days; afterward, the dosage was reduced in half every 2 days, and the MP therapy was terminated until 0.47 mg kg day). Kaplan-Meier method was used to compare the mortality between the 2 groups. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).The mortality of the prolonged MP therapy after pulse treatment group was lower than that of the pulse group (47.4% vs 63.3%; log-rank tests, P  =  .003). According to the multivariate Cox analysis, the prolonged MP therapy after pulse treatment was significantly associated with a lower mortality risk (HR: 0.31, 95% CI: 0.19-0.52, P < .001) compared with the pulse group. In addition, the prolonged MP therapy after pulse treatment caused more incidences of leucopenia than the pulse treatment alone (25.6% vs 11.7%, P  =  .04).The prolonged MP therapy after pulse treatment can reduce the mortality of moderate-to-severe PQ poisoning patients.

Risk factors associated with the occurrence of proximal humerus fractures in patients with rheumatoid arthritis: a custom strategy for preventing proximal humerus fractures.

PubMed

Ochi, Kensuke; Furuya, Takefumi; Ishibashi, Mina; Watanabe, Makiko; Ikari, Katsunori; Taniguchi, Atsuo; Yamanaka, Hisashi; Momohara, Shigeki

2016-02-01

To our knowledge, no prior report focused on the risk factors for proximal humerus fractures in patients with rheumatoid arthritis. The purpose of this study was to evaluate the association between potential risk factors and the occurrence of proximal humerus fractures in patients with rheumatoid arthritis. A total of 11,907 patients with rheumatoid arthritis were enrolled in our observational cohort rheumatoid arthritis study between 2000 and 2012. Self-reported proximal humerus fractures were verified using the patients' medical records. Cox proportional hazard models were used to analyze the independent contribution of risk factors to the occurrence of proximal humerus fractures. During follow-up (mean 5.6 years), 92 proximal humerus fractures were verified in 91 patients. Multivariate Cox regression analyses estimated that the hazard ratios of sustaining a proximal humerus fracture were 1.37 for every 10-year increase in age [95 % confidence interval (CI) 1.10-1.70; P < 0.01], 1.95 for increases in serum C-reactive protein levels (mg/100 mL; 95 % CI 1.15-3.34; P < 0.05), 2.13 for a history of fractures (95 % CI 1.34-3.40; P < 0.01), 1.07 for the daily prednisolone dose (per mg; 95 % CI 1.01-1.13; P < 0.05), and 1.97 for oral bisphosphonate use (95 % CI 1.20-3.23; P < 0.01). Better control of rheumatoid arthritis with a smaller daily prednisolone dose in elderly patients with a history of fractures may be important for preventing proximal humerus fractures.

Outcome of liver transplantation for hepatocellular carcinoma -- a single center experience.

PubMed

Iacob, R; Iacob, S; Gheorghe, L; Gheorghe, C; Hrehoreţ, D; Brașoveanu, V; Croitoru, A; Herlea, V; Popescu, I

2013-01-01

Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The aim of our study was to evaluate our experience regarding the clinical and pathological staging of HCC in patients who underwent LT, as well as recurrence free and overall survival. From January 2006 to December 2011, 38 patients with diagnosis of HCC, underwent LT in our Center. Demographic, clinical, imaging and pathologic information were recorded. A Cox proportional hazards survival analysis was performed in order to identify significant predictors of tumor recurrence and patient's death after LT. Eighteen patients (47.4%) in our study group were within Milan criteria. The mean follow-up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3- year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3-year overall survival rates were 83.5% and 63.6% respectively. No significant predictor for HCC recurrence was identified in our study group by survival analysis, taking into account 13 different variables. As independent predictors of patient'ss death after LT for HCC however, the presence of diabetes mellitus (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence after LT (p=0.03) were identified by multivariate Cox proportional hazards survival analysis. In our cohort HCC recurrence rate after LT was 13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence were significant predictors of poor overall survival after LT. Celsius.

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

PubMed

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

[Survival following the first admission in an integrated dual disorders treatment ward (IDDTW): preliminary results from a cohort study].

PubMed

Gimelfarb, Yuri; Becatel, Ety; Wolf, Aviva; Baruch, Yehuda

2014-01-01

Dual disorders (co-occurring severe mental illness [SMI] and substance abuse disorders in the same person) are extremely common among patients receiving mental health services. Dual disorders are associated with increased all-cause mortality, as compared with patients with SMI. Scientific evidence is lacking on the survival of dual disorders subjects, who had psychiatric inpatient care. To determine the long term survival rates of patients after the first admission in an IDDTW and to identify their baseline predictors. The charts of 258 subjects admitted to IDDTW during the period 2002-2004 were assessed at least 8 years after the first admission. Psychiatric diagnoses were established and grouped according to the International Statistical Classification of Diseases and Related Health Problems 10th edition (ICD-10). The Kaplan-Meier survival analysis was used to estimate the cumulative survival rates, and the predictive values of different variables were assessed by Cox proportional-hazards regression model. The cumulative 1-, 2-, 4-, 6- and 8-year survival rates of all subjects were 98.06%, 96.51%, 91.47, 86.43% and 81.78%, respectively, without statistically significant differences between subgroups of psychiatric diagnoses. Multivariate Cox regression analysis revealed that the age at death was the only independent predictor of all-cause mortality (hazard ratio = .96; 95% confidence interval .93 to .99; p < .009). Those of young age are at a particularly low risk of long term survival. More targeted health care is required to address the specific needs of this vulnerable subgroup. Further research of survival into specific risk groups is required.

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study

PubMed Central

2014-01-01

Background Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. Methods We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. Results A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14–0.92). Conclusions Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting. PMID:24884397

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study.

PubMed

Rosa, Regis G; Goldani, Luciano Z; dos Santos, Rodrigo P

2014-05-23

Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14-0.92). Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting.

4-protein signature predicting tamoxifen treatment outcome in recurrent breast cancer.

PubMed

De Marchi, Tommaso; Liu, Ning Qing; Stingl, Cristoph; Timmermans, Mieke A; Smid, Marcel; Look, Maxime P; Tjoa, Mila; Braakman, Rene B H; Opdam, Mark; Linn, Sabine C; Sweep, Fred C G J; Span, Paul N; Kliffen, Mike; Luider, Theo M; Foekens, John A; Martens, John W M; Umar, Arzu

2016-01-01

Estrogen receptor (ER) positive tumors represent the majority of breast malignancies, and are effectively treated with hormonal therapies, such as tamoxifen. However, in the recurrent disease resistance to tamoxifen therapy is common and a major cause of death. In recent years, in-depth proteome analyses have enabled identification of clinically useful biomarkers, particularly, when heterogeneity in complex tumor tissue was reduced using laser capture microdissection (LCM). In the current study, we performed high resolution proteomic analysis on two cohorts of ER positive breast tumors derived from patients who either manifested good or poor outcome to tamoxifen treatment upon recurrence. A total of 112 fresh frozen tumors were collected from multiple medical centers and divided into two sets: an in-house training and a multi-center test set. Epithelial tumor cells were enriched with LCM and analyzed by nano-LC Orbitrap mass spectrometry (MS), which yielded >3000 and >4000 quantified proteins in the training and test sets, respectively. Raw data are available via ProteomeXchange with identifiers PXD000484 and PXD000485. Statistical analysis showed differential abundance of 99 proteins, of which a subset of 4 proteins was selected through a multivariate step-down to develop a predictor for tamoxifen treatment outcome. The 4-protein signature significantly predicted poor outcome patients in the test set, independent of predictive histopathological characteristics (hazard ratio [HR] = 2.17; 95% confidence interval [CI] = 1.15 to 4.17; multivariate Cox regression p value = 0.017). Immunohistochemical (IHC) staining of PDCD4, one of the signature proteins, on an independent set of formalin-fixed paraffin-embedded tumor tissues provided and independent technical validation (HR = 0.72; 95% CI = 0.57 to 0.92; multivariate Cox regression p value = 0.009). We hereby report the first validated protein predictor for tamoxifen treatment outcome in recurrent ER-positive breast cancer. IHC further showed that PDCD4 is an independent marker. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Predictors of clinical outcome in pediatric oligodendroglioma: meta-analysis of individual patient data and multiple imputation.

PubMed

Wang, Kevin Yuqi; Vankov, Emilian R; Lin, Doris Da May

2018-02-01

OBJECTIVE Oligodendroglioma is a rare primary CNS neoplasm in the pediatric population, and only a limited number of studies in the literature have characterized this entity. Existing studies are limited by small sample sizes and discrepant interstudy findings in identified prognostic factors. In the present study, the authors aimed to increase the statistical power in evaluating for potential prognostic factors of pediatric oligodendrogliomas and sought to reconcile the discrepant findings present among existing studies by performing an individual-patient-data (IPD) meta-analysis and using multiple imputation to address data not directly available from existing studies. METHODS A systematic search was performed, and all studies found to be related to pediatric oligodendrogliomas and associated outcomes were screened for inclusion. Each study was searched for specific demographic and clinical characteristics of each patient and the duration of event-free survival (EFS) and overall survival (OS). Given that certain demographic and clinical information of each patient was not available within all studies, a multivariable imputation via chained equations model was used to impute missing data after the mechanism of missing data was determined. The primary end points of interest were hazard ratios for EFS and OS, as calculated by the Cox proportional-hazards model. Both univariate and multivariate analyses were performed. The multivariate model was adjusted for age, sex, tumor grade, mixed pathologies, extent of resection, chemotherapy, radiation therapy, tumor location, and initial presentation. A p value of less than 0.05 was considered statistically significant. RESULTS A systematic search identified 24 studies with both time-to-event and IPD characteristics available, and a total of 237 individual cases were available for analysis. A median of 19.4% of the values among clinical, demographic, and outcome variables in the compiled 237 cases were missing. Multivariate Cox regression analysis revealed subtotal resection (p = 0.007 [EFS] and 0.043 [OS]), initial presentation of headache (p = 0.006 [EFS] and 0.004 [OS]), mixed pathologies (p = 0.005 [EFS] and 0.049 [OS]), and location of the tumor in the parietal lobe (p = 0.044 [EFS] and 0.030 [OS]) to be significant predictors of tumor progression or recurrence and death. CONCLUSIONS The use of IPD meta-analysis provides a valuable means for increasing statistical power in investigations of disease entities with a very low incidence. Missing data are common in research, and multiple imputation is a flexible and valid approach for addressing this issue, when it is used conscientiously. Undergoing subtotal resection, having a parietal tumor, having tumors with mixed pathologies, and suffering headaches at the time of diagnosis portended a poorer prognosis in pediatric patients with oligodendroglioma.

Changes in autonomic nervous system activity, body weight, and percentage fat mass in the first year postpartum and factors regulating the return to pre-pregnancy weight.

PubMed

Izumi, Mie; Manabe, Emiko; Uematsu, Sayo; Watanabe, Ayako; Moritani, Toshio

2016-10-27

Many women become obese during pregnancy and the postpartum period. Weight gain and obesity in the general population are often attributed to abnormalities of autonomic nervous system (ANS) activity. The aim of this study was to clarify change in ANS activity, body weight, percentage fat mass (%FM), and body mass index (BMI) and the factors regulating the return to the pre-pregnancy weight in the first year postpartum. This study was conducted from 2012 to 2016 at the University Hospital of the Kyoto Prefectural University of Medicine and a nearby obstetrics and gynecology clinic in Japan. Body weight and %FM were measured in 51 women using a dual-frequency body composition measuring device. Heart rate variability and R-R spectral transformation were used as indicators of ANS activity. All parameters were calculated at three postpartum time points. Repeated measure analysis of variance was used for comparisons between measurement times. A multivariable Cox proportional hazards model was conducted to determine factors associated with the return to pre-pregnancy weight. Mean body weight, %FM, and BMI decreased significantly over time after delivery (P < 0.001, P < 0.001, P < 0.001). However, ANS activity did not differ among subjects in the three time points. 25.5 % of subjects had still not returned to their pre-pregnancy body weight by 150-270 days postpartum, and 19.6 % had not by 270-360 days postpartum. Normal-weight obesity (NWO; BMI of 18.5-25 kg/m 2 and %FM of ≥30 %) was observed in several subjects at each measurement. The results of analysis using a multivariable Cox proportional hazards model suggest that ANS activity had no significant correlation with the return to pre-pregnancy weight. The management of body weight and %FM after delivery is considered important. These findings suggest that ANS activity is not associated with the return to pre-pregnancy weight, albeit that sample size was small.

Outcomes of surgery for gastric cancer with distant metastases: a retrospective study from the SEER database

PubMed Central

Weng, Shanshan; Dong, Caixia; Zhu, Lizhen; Yang, Ziru; Zhong, Jing; Yuan, Ying

2017-01-01

Background The role of surgical therapy in gastric cancer patients with distant metastases remains controversial. This retrospective analysis was performed to identify whether gastric cancer patients with distant metastases might benefit from surgery. Patients and methods A total of 5185 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer with distant metastases from 2004 to 2009 were included. Patients were divided into the following three groups: patients who underwent resection of both the primary tumor and distant metastatic tumors (‘PMTR’ group), patients who only underwent resection of the primary tumor (‘PTR’ group) and patients who did not undergo any surgery (‘No surgery’ group). We employed the Kaplan-Meier analysis, the log-rank test and multivariate Cox proportional hazards regression models to estimate the survival time of the different groups. Results A total of 5185 patients had a median survival time (MST) of 9.0 months. The improvement in survival of the ‘PMTR’ and ‘PTR’ groups was significantly different compared with that of the ‘No surgery’ group (MST, 12.0 vs 12.0 vs 9.0 months, respectively, P<0.001; 1-year survival rate, 49.6% vs 49.1% vs 30.1%, respectively, P<0.001; 3-year survival rate, 12.5% vs 15.1% vs 5.8%, respectively, P<0.001), whereas no significant difference was found between the ‘PMTR’ group and ‘PTR’ group (P=0.642). Multivariate Cox proportional analysis showed that surgery was an independent prognostic factor (‘PMTR’, hazard ratio (HR) =0.648, 95% confidence interval (CI) 0.574-0.733, P<0.001; ‘PTR’, HR=0.631, 95% CI 0.583-0.684, P<0.001). Conclusions This retrospective analysis demonstrated that combined PTR and metastasectomy or PTR alone were independent prognostic factors for survival improvement in gastric cancer patients with distant metastases. Because no statistically significant difference in survival was observed between the ‘PMTR’ group and ‘PTR’ group, PTR, which is a more minor surgery, might be more appropriate than PMTR in clinical practice for gastric cancer patients with distant metastases. PMID:28008147

Eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio as an associated factor of high risk plaque on coronary computed tomography in patients without coronary artery disease.

PubMed

Nagahara, Yasuomi; Motoyama, Sadako; Sarai, Masayoshi; Ito, Hajime; Kawai, Hideki; Takakuwa, Yoko; Miyagi, Meiko; Shibata, Daisuke; Takahashi, Hiroshi; Naruse, Hiroyuki; Ishii, Junichi; Ozaki, Yukio

2016-07-01

Coronary computed tomography angiography (CCTA)-verified high risk plaque (HRP) characteristics including positive remodeling and low attenuation plaque have been associated with acute coronary syndromes. Several studies reported that the n-3 polyunsaturated fatty acids have been associated with cardiovascular events. However, the relationship between serum eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio and CCTA-verified HRP in patients without known coronary artery disease (CAD) is unclear. We aimed at investigating the relation between EPA/AA and CCTA-verified HRP in patients without known CAD. We included 193 patients undergoing CCTA without known CAD (65.5 ± 12.0 years, 55.0% male). No patient has been treated with EPA. The relation of coronary risk factors, lipid profile, high-sensitivity C-reactive protein, coronary artery calcification score (CACS), number of vessel disease, plaque burden, and EPA/AA with the presence of HRP was evaluated by logistic regression analysis. Incremental value of EPA/AA to predict HRP was also analyzed by C-index, NRI, and IDI. A Cox proportional hazards model was used to estimate the time to cardiovascular event. HRP was observed in 37 (19%) patients. Multivariable logistic regression analysis revealed that current smoking (OR 2.58; p=0.046), number of vessel disease (OR 1.87; p=0.031), and EPA/AA ratio (OR 0.65; p=0.0006) were independent associated factors of HRP on CCTA. Although the addition of EPA/AA to the baseline model did not significantly improve C-index, both NRI (0.60, p=0.0049) and IDI (0.054, p=0.0072) were significantly improved. Patients with HRP had significantly higher rate of events compared with patients without HRP (14% vs. 3%, Logrank p=0.0004). On multivariable Cox hazard analysis, baseline EPA/AA ratio was an independent predictor (HR 0.57, p=0.047). Low EPA/AA was an associated factor of HRP on CCTA in patients without CAD. In addition to conventional coronary risk factors and CACS, EPA/AA and CCTA might be useful for risk stratification of CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.

PubMed

Cobleigh, Melody A; Tabesh, Bita; Bitterman, Pincas; Baker, Joffre; Cronin, Maureen; Liu, Mei-Lan; Borchik, Russell; Mosquera, Juan-Miguel; Walker, Michael G; Shak, Steven

2005-12-15

This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.

Red meat consumption and risk of heart failure in male physicians.

PubMed

Ashaye, A; Gaziano, J; Djoussé, L

2011-12-01

Heart failure (HF) remains a major public health issue. Red meat and dietary heme iron have been associated with an increased risk of coronary heart disease and hypertension, two major risk factors for HF. However, it is not known whether red meat intake influences the risk of HF. We therefore examined the association between red meat consumption and incident HF. We prospectively studied 21,120 apparently healthy men (mean age 54.6 y) from the Physicians' Health Study (1982-2008). Red meat was assessed by an abbreviated food questionnaire and incident HF was ascertained through annual follow-up questionnaires. We used Cox proportional hazard models to estimate hazard ratios. In a multivariable model, there was a positive and graded relation between red meat consumption and HF [hazard ratio (95% CI) of 1.0 (reference), 1.02 (0.85-1.22), 1.08 (0.90-1.30), 1.17 (0.97-1.41), and 1.24 (1.03-1.48) from the lowest to the highest quintile of red meat, respectively (p for trend 0.007)]. This association was observed for HF with (p for trend 0.035) and without (p for trend 0.038) antecedent myocardial infarction. Our data suggest that higher intake of red meat is associated with an increased risk of HF. Published by Elsevier B.V.

Coffee Intake and Incidence of Erectile Dysfunction.

PubMed

Lopez, David S; Liu, Lydia; Rimm, Eric B; Tsilidis, Konstantinos K; de Oliveira Otto, Marcia; Wang, Run; Canfield, Steven; Giovannucci, Edward

2018-05-01

Coffee intake is suggested to have a positive impact on chronic diseases, yet its role in urological diseases such as erectile dysfunction (ED) remains unclear. We investigated the association of coffee intake with incidence of ED by conducting the Health Professionals Follow-Up Study, a prospective analysis of 21,403 men aged 40-75 years old. Total, regular, and decaffeinated coffee intakes were self-reported on food frequency questionnaires. ED was assessed by mean values of questionnaires in 2000, 2004 and 2008. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident ED (n = 7,298). No significant differences were identified for patients with incident ED after comparing highest (≥4 cups/day) with lowest (0 cups/day) categories of total (hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.90, 1.11) and regular coffee intakes (HR = 1.00, 95% CI: 0.89, 1.13). When comparing the highest category with lowest category of decaffeinated coffee intake, we found a 37% increased risk of ED (HR = 1.37, 95% CI: 1.08, 1.73), with a significant trend (P trend = 0.02). Stratified analyses also showed an association among current smokers (P trend = 0.005). Overall, long-term coffee intake was not associated with risk of ED in a prospective cohort study.

Social relationships and risk of incident mild cognitive impairment in U.S. Alzheimer's disease centers.

PubMed

Brenowitz, Willa D; Kukull, Walter A; Beresford, Shirley A A; Monsell, Sarah E; Williams, Emily C

2014-01-01

Social relationships are hypothesized to prevent or slow cognitive decline. We sought to evaluate associations between social relationships and mild cognitive impairment (MCI). Participants from the National Alzheimer's Coordinating Center database who were cognitively normal, aged 55 and older at baseline, and had at least 2 in-person visits (n=5335) were included. Multivariable Cox proportional hazard models evaluated the association between 4 social relationships at baseline (marital status, living situation, having children, and having siblings) and risk of developing MCI (on the basis of clinician diagnosis following established criteria). Primary models were adjusted for baseline demographics. Participants were followed, on average, for 3.2 years; 15.2% were diagnosed with MCI. Compared with married participants, risk of MCI was significantly lower for widowed participants (hazard ratio: 0.87; 95% confidence interval: 0.76, 0.99) but not for divorced/separated or never-married participants. Compared with living with a spouse/partner, risk of MCI was significantly higher for living with others (hazard ratio: 1.35; 95% confidence interval: 1.03, 1.77) but not for living alone. Risk of MCI was not associated with having children or having siblings. These results did not consistently identify social relationships as a strong risk factor for, or independent clinical predictor of, MCI.

Muscular strength and incident hypertension in normotensive and prehypertensive men.

PubMed

Maslow, Andréa L; Sui, Xuemei; Colabianchi, Natalie; Hussey, Jim; Blair, Steven N

2010-02-01

The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. This study evaluated the strength-HTN association with and without accounting for CRF. Participants were 4147 men (age = 20-82 yr) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a one-repetition maximal leg and a one-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals of incident HTN events according to exposure categories. During a mean follow-up of 19 yr, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HR of HTN in normotensive men comparing middle- and high-strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HR of HTN in baseline prehypertensive men comparing middle- and high-strength thirds to the lowest third were significant at 0.73 and 0.72 (P = 0.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (P = 0.26). The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF.

Prognostic value of inflammation-based markers in patients with pancreatic cancer administered gemcitabine and erlotinib.

PubMed

Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck

2016-07-15

To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.

Racial differences in colorectal cancer survival at a safety net hospital.

PubMed

Tapan, Umit; Lee, Shin Yin; Weinberg, Janice; Kolachalama, Vijaya B; Francis, Jean; Charlot, Marjory; Hartshorn, Kevan; Chitalia, Vipul

2017-08-01

While racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood. We examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospital's electronic medical record. Survival differences among different racial and ethnic groups were examined graphically using Kaplan-Meier analysis. A univariate cox proportional hazards model and a multivariable adjusted model were generated. Black patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01-2.90, p=0.0467) for death. Though response to therapy emerged as a strong predictor of survival (HR=0.4, CI=0.2-0.7, p=0.0021), it was comparable between Blacks and Whites. Despite presumed equal access to healthcare and socioeconomic status within a safety-net hospital system, our results reinforce findings from previous studies showing lower colorectal cancer survival in Black patients, and also point to the importance of investigating other factors such as genetic and pathologic differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Central nervous system medication use and incident mobility limitation in community elders: the Health, Aging, and Body Composition study.

PubMed

Boudreau, Robert M; Hanlon, Joseph T; Roumani, Yazan F; Studenski, Stephanie A; Ruby, Christine M; Wright, Rollin M; Hilmer, Sarah N; Shorr, Ronald I; Bauer, Douglas C; Simonsick, Eleanor M; Newman, Anne B

2009-10-01

To evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation. This 5-year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well-functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in-home or in-clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health behaviors, health status, and common indications for CNS medications. Each year at least 13.9% of participants used a CNS medication. By year 6, overall 49% had developed incident mobility limitation. In multivariable models, CNS medication users compared to never users showed a higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR) 1.28; 95% confidence interval (CI) 1.12-1.47). Similar findings of increased risk were seen in analyses examining dose- and duration-response relationships. CNS medication use is independently associated with an increased risk of future incident mobility limitation in community dwelling elderly. Further studies are needed to determine the impact of reducing CNS medication exposure on mobility problems. 2009 John Wiley & Sons, Ltd.

Estimation of variance in Cox's regression model with shared gamma frailties.

PubMed

Andersen, P K; Klein, J P; Knudsen, K M; Tabanera y Palacios, R

1997-12-01

The Cox regression model with a shared frailty factor allows for unobserved heterogeneity or for statistical dependence between the observed survival times. Estimation in this model when the frailties are assumed to follow a gamma distribution is reviewed, and we address the problem of obtaining variance estimates for regression coefficients, frailty parameter, and cumulative baseline hazards using the observed nonparametric information matrix. A number of examples are given comparing this approach with fully parametric inference in models with piecewise constant baseline hazards.

Prognostic value of tumor size in gastric cancer: an analysis of 2,379 patients.

PubMed

Guo, Pengtao; Li, Yangming; Zhu, Zhi; Sun, Zhe; Lu, Chong; Wang, Zhenning; Xu, Huimian

2013-04-01

Tumor size has been included into the staging systems of many solid tumors, such as lung and breast. However, tumor size is not integrated in the staging of gastric cancer, and its prognostic value for gastric cancer needs to be reappraised. A total of 2,379 patients who received radical resection for histopathologically confirmed gastric adenocarcinoma were enrolled in the present study. Tumor size, originally presented as continuous variable, was categorized into small gastric cancer (SGC) group and large gastric cancer (LGC) group using an optimal cutoff point determined by Cox proportional hazards model. The associations between tumor size and other clinicopathological factors were checked using Chi-square test. Survival of gastric cancer patients was estimated by using univariate Kaplan-Meier method, and the survival difference was checked by using the log-rank test. The significant clinicopathological factors were included into the Cox proportional hazards model to determine the independent prognostic factors, and their hazard ratios were calculated. With the optimal cutoff point of 4 cm, tumor size was categorized into SGC group (≤ 4 cm) and LGC group (>4 cm). Tumor size closely correlated with age, tumor location, macroscopic type, Lauren classification, and lymphatic vessel invasion. Moreover, tumor size was also significantly associated with depth of tumor invasion and status of regional lymph nodes. The 5-year survival rate was 68.7 % for SGC group which was much higher than 40.2 % for LGC group. Univariate analysis showed that SGC had a better survival than LGC, mainly for patients with IIA, IIB, and IIIA stage. Multivariate analysis revealed that tumor size as well as age, tumor location, macroscopic type, Lauren classification, lymphatic vessel invasion, depth of tumor invasion, and status of regional lymph nodes were independent prognostic factors for gastric cancer. Tumor size is a reliable prognostic factor for patients with gastric cancer, and the measurement of tumor size would be helpful to the staging and management of gastric cancer.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bingham, Brian; Orton, Andrew; Boothe, Dustin

Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysismore » was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.« less

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

PubMed Central

Finch, Natalie A.; Zasowski, Evan J.; Murray, Kyle P.; Mynatt, Ryan P.; Zhao, Jing J.; Yost, Raymond; Pogue, Jason M.

2017-01-01

ABSTRACT Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. PMID:28923869

Association of time-to-surgery with outcomes in clinical stage I-II pancreatic adenocarcinoma treated with upfront surgery.

PubMed

Swords, Douglas S; Zhang, Chong; Presson, Angela P; Firpo, Matthew A; Mulvihill, Sean J; Scaife, Courtney L

2018-04-01

Time-to-surgery from cancer diagnosis has increased in the United States. We aimed to determine the association between time-to-surgery and oncologic outcomes in patients with resectable pancreatic ductal adenocarcinoma undergoing upfront surgery. The 2004-2012 National Cancer Database was reviewed for patients undergoing curative-intent surgery without neoadjuvant therapy for clinical stage I-II pancreatic ductal adenocarcinoma. A multivariable Cox model with restricted cubic splines was used to define time-to-surgery as short (1-14 days), medium (15-42), and long (43-120). Overall survival was examined using Cox shared frailty models. Secondary outcomes were examined using mixed-effects logistic regression models. Of 16,763 patients, time-to-surgery was short in 34.4%, medium in 51.6%, and long in 14.0%. More short time-to-surgery patients were young, privately insured, healthy, and treated at low-volume hospitals. Adjusted hazards of mortality were lower for medium (hazard ratio 0.94, 95% confidence interval, .90, 0.97) and long time-to-surgery (hazard ratio 0.91, 95% confidence interval, 0.86, 0.96) than short. There were no differences in adjusted odds of node positivity, clinical to pathologic upstaging, being unresectable or stage IV at exploration, and positive margins. Medium time-to-surgery patients had higher adjusted odds (odds ratio 1.11, 95% confidence interval, 1.03, 1.20) of receiving an adequate lymphadenectomy than short. Ninety-day mortality was lower in medium (odds ratio 0.75, 95% confidence interval, 0.65, 0.85) and long time-to-surgery (odds ratio 0.72, 95% confidence interval, 0.60, 0.88) than short. In this observational analysis, short time-to-surgery was associated with slightly shorter OS and higher perioperative mortality. These results may suggest that delays for medical optimization and referral to high volume surgeons are safe. Published by Elsevier Inc.

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

PubMed

Finch, Natalie A; Zasowski, Evan J; Murray, Kyle P; Mynatt, Ryan P; Zhao, Jing J; Yost, Raymond; Pogue, Jason M; Rybak, Michael J

2017-12-01

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure. Copyright © 2017 American Society for Microbiology.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more appropriate patient follow up according to risk stratification. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Age-Dependent Association Between Pre-transplant Blood Transfusion and Outcomes of Pediatric Heart Transplantation.

PubMed

McKee, C; Tumin, D; Alevriadou, B R; Nicol, K K; Yates, A R; Hayes, D; Tobias, J D

2018-04-01

Avoidance of red blood cell (RBC) transfusions in patients awaiting heart transplantation (HTx) has been suggested to minimize the risk of allosensitization. Although recent studies have suggested that an immature immune system in younger HTx recipients may reduce risks associated with RBC transfusion, the role of age in moderating the influence of transfusion on HTx outcomes remains unclear. We used available data from a national transplant registry to explore whether the association between pre-transplant transfusions and outcomes of pediatric HTx varies by patient age. De-identified data were obtained from the United Network for Organ Sharing registry, including first-time recipients of isolated HTx performed at age 0-17 years in 1995-2015. The primary exposure was receiving blood transfusions within 2 weeks prior to HTx. Patient survival after HTx was evaluated using multivariable Cox proportional hazards, where age at transplant was interacted with exposure to pre-transplant transfusion. Age-specific hazard ratios (HRs) of pre-transplant transfusion were plotted across ages at transplant. There were 4883 patients meeting inclusion criteria, of whom 1258 died during follow-up (mean follow-up duration 6 ± 5 years). Patients receiving pre-transplant transfusions were distinguished by younger age, higher prevalence of prior cardiac surgery, greater likelihood of being in the intensive care unit, and greater use of left ventricular assist device bridge to transplant. In multivariable analysis, pre-transplant transfusions were associated with increased mortality hazard among infants < 1 year of age (HR = 1.46; 95% CI 1.23, 1.74; p < 0.001). For each additional year of age, the excess hazard associated with pre-transplant transfusions decreased by 3% (interaction HR = 0.97; 95% CI 0.98, 0.99; p = 0.003). By age 8, the association between pre-transplant transfusions and post-transplant mortality was no longer statistically significant (HR = 1.15; 95% CI 0.99, 1.32; p = 0.060). Pre-transplant transfusions were associated with increased mortality hazard only among younger children (age < 8 years) undergoing HTx. These data support the current practices of transfusion avoidance prior to HTx, particularly in younger patients.

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort.

PubMed

Budhathoki, Sanjeev; Hidaka, Akihisa; Yamaji, Taiki; Sawada, Norie; Tanaka-Mizuno, Sachiko; Kuchiba, Aya; Charvat, Hadrien; Goto, Atsushi; Kojima, Satoshi; Sudo, Natsuki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro; Iwasaki, Motoki

2018-03-07

To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. Nine public health centre areas across Japan. 3301 incident cases of cancer and 4044 randomly selected subcohort participants. Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. Incidence of overall or site specific cancer. Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Prescription trends and psychiatric symptoms following first receipt of one of seven common antiepileptic drugs in general practice.

PubMed

Josephson, Colin B; Engbers, Jordan D T; Jette, Nathalie; Patten, Scott B; Sajobi, Tolulope T; Marshall, Deborah; Lowerison, Mark; Wiebe, Samuel

2018-05-09

We sought to examine the risk of psychiatric symptoms associated with a first prescription for specific antiepileptic drugs (AEDs) used in monotherapy in a general cohort of patients with epilepsy. We used The Health Improvement Network database (comprising the years 2000-2012) to identify incident patients with epilepsy. The index date was that on which they met the case definition for epilepsy, and analyses only included patients who remained on monotherapy or received no AED therapy following diagnosis to avoid confounding by polytherapy. Psychiatric symptoms were defined using mental health clinical or treatment (medical or therapeutic) code. We analyzed the AED of interest as a time-varying covariate in multivariate Cox proportional hazard regression models controlling for confounding factors. We identified 9595 patients with incident epilepsy, 7400 of whom (77%) received a first-recorded AED prescription. Prescriptions for newer generation AEDs (lamotrigine and levetiracetam) steadily increased (constituting over 30% of all AED prescriptions by 2012) while valproate use significantly declined in females (~40% in 2002 to just over 20% by 2012). A total of 2190 patients were first exposed to carbamazepine (29.3%) and 222 to lamotrigine (3%), both of which were associated with a lower hazard of any coded psychiatric symptom or disorder in multivariate analyses (hazard ratio [HR]: 0.84, 95% confidence interval [95% CI]: 0.73-0.97; p = 0.02 and HR: 0.83, 95% CI: 0.70-0.99; p = 0.03, respectively, for carbamazepine and lamotrigine). Carbamazepine was also associated with a lower hazard for depression (HR: 0.81; 95% CI: 0.69-0.96; p = 0.013) and anxiety (HR: 0.77; 95% CI: 0.63-0.95; p = 0.013) in secondary analyses. This study provides evidence that carbamazepine and lamotrigine are associated with lower hazards for psychiatric symptoms following a diagnosis of epilepsy. These estimates can be used in clinical settings, and the precision should improve with more contemporary data that include larger proportions of newer generation AEDs. Copyright © 2018 Elsevier Inc. All rights reserved.

An evaluation of treatment strategies for head and neck cancer in an African American population.

PubMed

Ignacio, D N; Griffin, J J; Daniel, M G; Serlemitsos-Day, M T; Lombardo, F A; Alleyne, T A

2013-07-01

This study evaluated treatment strategies for head and neck cancers in a predominantly African American population. Data were collected utilizing medical records and the tumour registry at the Howard University Hospital. Kaplan-Meier method was used for survival analysis and Cox proportional hazards regression analysis predicted the hazard of death. Analysis revealed that the main treatment strategy was radiation combined with platinum for all stages except stage I. Cetuximab was employed in only 1% of cases. Kaplan-Meier analysis revealed stage II patients had poorer outcome than stage IV while Cox proportional hazard regression analysis (p = 0.4662) showed that stage I had a significantly lower hazard of death than stage IV (HR = 0.314; p = 0.0272). Contributory factors included tobacco and alcohol but body mass index (BMI) was inversely related to hazard of death. There was no difference in survival using any treatment modality for African Americans.

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients.

PubMed

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Dietrich, Dimo

2017-01-01

This study evaluates promoter methylation of the programmed cell death ligand 1 (PD-L1) as a biomarker in a cohort of 383 colorectal cancer patients. PD-L1 methylation (m PD-L1 ) was inversely correlated with PD-L1 mRNA expression ( p = 0.001) and was associated with significantly shorter overall survival (OS, p = 0.003) and recurrence-free survival (RFS, p < 0.001). In age-stratified multivariate Cox proportional hazards analyses including sex, tumor, nodal, distant metastasis categories, microsatellite instability (MSI)-status, and PD-L1 mRNA, m PD-L1 is classified as an independent prognostic factor (OS: p = 0.030; RFS: p < 0.001). Further studies are needed to evaluate PD-L1 methylation as a biomarker for response prediction of immunotherapies targeting the PD-1/PD-L1 axis.

Adjusted variable plots for Cox's proportional hazards regression model.

PubMed

Hall, C B; Zeger, S L; Bandeen-Roche, K J

1996-01-01

Adjusted variable plots are useful in linear regression for outlier detection and for qualitative evaluation of the fit of a model. In this paper, we extend adjusted variable plots to Cox's proportional hazards model for possibly censored survival data. We propose three different plots: a risk level adjusted variable (RLAV) plot in which each observation in each risk set appears, a subject level adjusted variable (SLAV) plot in which each subject is represented by one point, and an event level adjusted variable (ELAV) plot in which the entire risk set at each failure event is represented by a single point. The latter two plots are derived from the RLAV by combining multiple points. In each point, the regression coefficient and standard error from a Cox proportional hazards regression is obtained by a simple linear regression through the origin fit to the coordinates of the pictured points. The plots are illustrated with a reanalysis of a dataset of 65 patients with multiple myeloma.

Flexible mixture modeling via the multivariate t distribution with the Box-Cox transformation: an alternative to the skew-t distribution

PubMed Central

Lo, Kenneth

2011-01-01

Cluster analysis is the automated search for groups of homogeneous observations in a data set. A popular modeling approach for clustering is based on finite normal mixture models, which assume that each cluster is modeled as a multivariate normal distribution. However, the normality assumption that each component is symmetric is often unrealistic. Furthermore, normal mixture models are not robust against outliers; they often require extra components for modeling outliers and/or give a poor representation of the data. To address these issues, we propose a new class of distributions, multivariate t distributions with the Box-Cox transformation, for mixture modeling. This class of distributions generalizes the normal distribution with the more heavy-tailed t distribution, and introduces skewness via the Box-Cox transformation. As a result, this provides a unified framework to simultaneously handle outlier identification and data transformation, two interrelated issues. We describe an Expectation-Maximization algorithm for parameter estimation along with transformation selection. We demonstrate the proposed methodology with three real data sets and simulation studies. Compared with a wealth of approaches including the skew-t mixture model, the proposed t mixture model with the Box-Cox transformation performs favorably in terms of accuracy in the assignment of observations, robustness against model misspecification, and selection of the number of components. PMID:22125375

Flexible mixture modeling via the multivariate t distribution with the Box-Cox transformation: an alternative to the skew-t distribution.

PubMed

Lo, Kenneth; Gottardo, Raphael

2012-01-01

Cluster analysis is the automated search for groups of homogeneous observations in a data set. A popular modeling approach for clustering is based on finite normal mixture models, which assume that each cluster is modeled as a multivariate normal distribution. However, the normality assumption that each component is symmetric is often unrealistic. Furthermore, normal mixture models are not robust against outliers; they often require extra components for modeling outliers and/or give a poor representation of the data. To address these issues, we propose a new class of distributions, multivariate t distributions with the Box-Cox transformation, for mixture modeling. This class of distributions generalizes the normal distribution with the more heavy-tailed t distribution, and introduces skewness via the Box-Cox transformation. As a result, this provides a unified framework to simultaneously handle outlier identification and data transformation, two interrelated issues. We describe an Expectation-Maximization algorithm for parameter estimation along with transformation selection. We demonstrate the proposed methodology with three real data sets and simulation studies. Compared with a wealth of approaches including the skew-t mixture model, the proposed t mixture model with the Box-Cox transformation performs favorably in terms of accuracy in the assignment of observations, robustness against model misspecification, and selection of the number of components.

Impact of socioeconomic status on survival for patients with anal cancer.

PubMed

Lin, Daniel; Gold, Heather T; Schreiber, David; Leichman, Lawrence P; Sherman, Scott E; Becker, Daniel J

2018-04-15

Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA. Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt. A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20). MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018;124:1791-7. © 2018 American Cancer Society. © 2018 American Cancer Society.

Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

PubMed

Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

2015-03-01

We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (≥440 ms in men and ≥460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ≥244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population. © 2014 American Heart Association, Inc.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

PubMed

Bibert, Stéphanie; Wojtowicz, Agnieszka; Taffé, Patrick; Manuel, Oriol; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F; Hoffmann, Matthias; Kaiser, Laurent; Osthoff, Michael; Cavassini, Matthias; Bochud, Pierre-Yves

2014-08-24

Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir < 00 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

Conditional Survival in Anal Carcinoma Using the National Population-Based Survey of Epidemiology and End Results Database (1988-2012).

PubMed

Kim, Ellen; Kim, Jong S; Choi, Mehee; Thomas, Charles R

2016-04-01

Conditional survival can provide valuable information for both patients and healthcare providers about the changing prognosis in surviving patients over time. This study estimated conditional survival for patients with anal cancer in the United States through analysis of a national population-based cancer registry. Log-rank test identified significant covariates of cause-specific survival (defined as time from diagnosis until death from anal cancer). Significant covariates were considered in the multivariable regression of cause-specific survival using Cox proportional hazards models. Covariates included cancer stage and demographic variables. Patients in Surveillance, Epidemiology, and End Results regions diagnosed with anal squamous cell carcinoma as their first and only cancer diagnosis from 1988 to 2012 were selected from this database, and 5145 patients were included in the retrospective cohort study. Five-year conditional survival stratified by each variable in the final Cox models was measured : The final multivariable models of overall and cause-specific survivals included stage, grade, sex, age, race, and relationship status. Over the first 6 years after diagnosis, conditional survival of distant stage increased from 37% to 89%, whereas regional stage increased from 65% to 93% and localized stage increased from 84% to 96%. The other variables had increasing prognosis as well, but the subgroups increased at a more similar rate over time. The data source used does not include information on chemotherapy treatment, patient comorbidities, or socioeconomic status. Conditional survival showed improvement over time. Patients with advanced stage had the greatest improvement in conditional survival. This is the first study to provide specific conditional survival probabilities for patients with anal cancer.

Risk factors of flare in rheumatoid arthritis patients with both clinical and ultrasonographic remission: a retrospective study from China.

PubMed

Han, Jingjing; Geng, Yan; Deng, Xuerong; Zhang, Zhuoli

2017-08-01

Ultrasonographic remission in addition to clinical remission is probably becoming a new target in the treatment of rheumatoid arthritis. The current study aimed to investigate the risk factors of flare in RA patients who achieved both clinical and ultrasonographic remission. RA patients fulfilled both clinical remission and ultrasonographic remissions were retrospectively enrolled in this study. Baseline clinical, laboratory, and ultrasonographic data were collected. Durations of clinical remission before enrollment and medication strategy during follow-up were recorded. Differences between the flare and the non-flare group were analyzed. Risk factors of flare were assessed with univariate and multivariate Cox proportional hazards models. One hundred and twenty-one RA patients were included. Forty-eight patients relapsed during a median follow-up period of 12.3 months. The flare group had higher percentage of females, shorter duration of clinical remission before enrollment, higher baseline ESR and DAS28 (ESR), and lower baseline gray scale score. Univariate Cox regression revealed female, short duration of remission, high DAS28 (ESR), and failure to achieve 2010 ACR/EULAR remission criteria were risk factors of flare. Furthermore, multivariate analysis showed short duration of remission was the only independent risk factor of flare (HR 0.93, 95% CI 0.88-0.98, P = 0.007). One more month in duration of remission led to a reduction in flare of 7.3%. Short duration of remission at baseline could be an independent risk factor of flare in RA patients who achieved both clinical and ultrasonographic remission, which implicates the significance of sustained remission in the prognosis of RA patients.

Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer.

PubMed

Fan, Heng; Zhu, Jian-Hua; Yao, Xue-Qing

2018-05-01

Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan-Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan-Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.

[Neutrophil to lymphocyte ratio in peripheral blood: a novel independent prognostic factor in patients with head and neck squamous cell carcinoma].

PubMed

Wu, F; Wu, L L; Zhu, L X

2017-01-23

Objective: To investigate whether neutrophil to lymphocyte ratio (NLR) in peripheral blood can be an independent prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Clinical data of 97 HNSCC patients who received surgical treatment in our department between January 2008 and January 2012 were analyzed retrospectively. The 97 patients were divided into low NLR group (NLR≤5, n =69) and high NLR group (NLR>5, n =28) according to the NLR in preoperative peripheral blood. The relationships of NLR and clinicopathological features were analyzed. Kaplan-Meier method was used for univariate survival analysis and Cox proportional hazard model for multivariate survival analysis. Results: The clinical stages were significantly different between high NLR group and low NLR group ( P <0.05), however, the age, gender, location, lymph node metastasis, smoking and alcohol of the two groups showed no significant differences ( P > 0.05 of all). Univariate survival analysis showed that smoking, lymph node metastasis, clinical stage and NLR value were risk factors for 3-year overall survival (OS) rate and relapse-free survival (RFS) rate of HNSCC patients ( P <0.05). The OS rate of high NLR and low NLR groups was 42.9% and 91.3%, and the RFS rate was 44.2% and 80.1%, respectively, with a statistically significant difference ( P <0.05 for both). Cox multivariate survival analysis showed that clinical stage and NLR were independent factors for prognostic evaluation of HNSCC patients ( P <0.05 for both). Conclusions: NLR level is significantly associated with clinical stage of HNSCC. High NLR is an independent prognostic rick factor and plays an important role in prognostic evaluation of HNSCC patients.

Chemotherapy Versus Chemoradiation for Node-Positive Bladder Cancer: Practice Patterns and Outcomes from the National Cancer Data Base

PubMed Central

Haque, Waqar; Verma, Vivek; Butler, E. Brian; Teh, Bin S.

2017-01-01

Background: Management of clinically node-positive bladder cancer (cN+ BC) is poorly defined; national guidelines recommend chemotherapy (CT) alone or chemoradiation (CRT). Objective: Using a large, contemporary dataset, we evaluated national practice patterns and outcomes of CT versus CRT to elucidate the optimal therapy for this patient population. Methods: The National Cancer Data Base (NCDB) was queried (2004–2013) for patients diagnosed with cTanyN1-3M0 BC. Patients were divided into two groups: CT alone or CRT. Statistics included multivariable logistic regression to determine factors predictive of receiving additional radiotherapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. Propensity score matching was performed to assess groups in a balanced manner while reducing indication biases. Results: Of 1,783 total patients, 1,388 (77.8%) underwent CT alone, and 395 (22.2%) CRT. Although patients receiving CRT tended to be of higher socioeconomic status, they were more likely older (p = 0.053), higher T stage, N1 (versus N2) disease, squamous histology, and treated at a non-academic center (p < 0.05). Median overall survival (OS) was 19.0 months and 13.8 months (p < 0.001) for patients receiving CRT or CT, respectively. On Cox multivariate analysis, receipt of CRT was independently associated with improved survival (p < 0.001). Outcome improvements with CRT persisted on evaluation of propensity-matched populations (p < 0.001). Conclusions: CRT is underutilized in the United States for cN+ BC but is independently associated with improved survival despite being preferentially administered to a somewhat higher-risk population. PMID:29152552

Dyspnea predicts mortality among patients undergoing coronary computed tomographic angiography.

PubMed

Nakanishi, Rine; Gransar, Heidi; Rozanski, Alan; Rana, Jamal S; Cheng, Victor Y; Thomson, Louise E J; Miranda-Peats, Romalisa; Dey, Damini; Hayes, Sean W; Friedman, John D; Min, James K; Berman, Daniel S

2016-02-01

The prognostic implications of dyspnea and typical angina in patients referred for coronary CT angiography have not been examined. We examined features associated with incident mortality risk among individuals undergoing coronary computed tomographic angiography (CCTA) presenting with dyspnea, typical angina, and neither of these symptoms. 1147 consecutive individuals without known CAD (mean 61 years, 61.6 %men) undergoing CCTA comprised the study population 132 with dyspnea, 218 with typical angina, and 797 without dyspnea or typical angina (reference group). Mortality risk in relation to dyspnea or typical angina was evaluated with multivariable Cox proportional hazards models compared to reference. In addition, the prognosis associated with dyspnea or typical angina was assessed among age matched subgroups. Patients with dyspnea had a greater prevalence of C70 % stenosis (p\\0.001) and coronary segments with plaque (p = 0.02) compared to the other two groups. During a follow-up of 3.1 years, 52 individuals died. By multivariable Cox models, compared to patients in reference group, dyspnea patients experienced higher mortality (HR 2.0, 95 % CI 1.0–4.0, p = 0.049) while typical angina patients did not (HR 1.1, 95 % CI 0.6–2.3, p = 0.76). In the matched group, the patients with dyspnea (HR 2.2, 95 % CI 1.1–4.3, p = 0.03) still had significantly reduced survival compared to the other two groups, while those with typical angina did not (HR 1.2, 95 % CI 0.6–2.6,p = 0.62). Dyspnea is associated with increased mortality ate compared to patients with typical angina and those with neither of these symptoms among patients undergoing CCTA.

The relationship of age-adjusted Charlson comorbidity ındex and diurnal variation of blood pressure.

PubMed

Kalaycı, Belma; Erten, Yunus Turgay; Akgün, Tunahan; Karabag, Turgut; Kokturk, Furuzan

2018-03-05

Charlson Comorbidity index (CCI) is a scoring system to predict prognosis and mortality. It exhibits better utility when combined with age, age-adjusted Charlson Comorbidity Index (ACCI). The aim of this study was to evaluate the relationship between ACCI and diurnal variation of blood pressure parameters in hypertensive patients and normotensive patients. We enrolled 236 patients. All patients underwent a 24-h ambulatory blood pressure monitoring (ABPM) for evaluation of dipper or non-dipper pattern. We searched the correlation between ACCI and dipper or non-dipper pattern and other ABPM parameters. To further investigate the role of these parameters in predicting survival, a multivariate analysis using the Cox proportional hazard model was performed. 167 patients were in the hypertensive group (87 patients in non-dipper status) and 69 patients were in the normotensive group (41 patients in non-dipper status) of all study patients. We found a significant difference and negative correlation between AACI and 24-h diastolic blood pressure (DBP), awake DBP, awake mean blood pressure (MBP) and 24-h MBP and awake systolic blood pressure(SBP). Night decrease ratio of blood pressure had also a negative correlation with ACCI (p = 0.003, r = -0.233). However, we found a relationship with non-dipper pattern and ACCI in the hypertensive patients (p = 0.050). In multivariate Cox analysis sleep MBP was found related to mortality like ACCI (p = 0.023, HR = 1.086, %95 CI 1.012-1.165) Conclusion: ACCI was statistically significantly higher in non-dipper hypertensive patients than dipper hypertensive patients while ACCI had a negative correlation with blood pressure. Sleep MBP may predict mortality.

Serum thymidine kinase 1 levels predict cancer-free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

PubMed Central

CHEN, FEIYU; TANG, LILI; XIA, TING; HE, ELLEN; HU, GUOZHU; LI, YUAN; ZHANG, MING; ZHOU, JI; ERIKSSON, STAFFAN; SKOG, SVEN

2013-01-01

In this study, the use of serum thymidine kinase 1 protein (STK1p) concentration for the prognosis of the overall survival of patients with locally advanced breast cancer (n=51) following routine treatment (neoadjuvant treatment, surgery and chemotherapy) was investigated. The patients were followed up for 44 months and the STK1p values were determined by a high-sensitivity enhanced chemiluminescence (ECL) dot blot assay. The variables investigated in relation to metastasis and survival were STK1p, clinical stage, tumor size and age, by the Kaplan-Meier method, the log-rank test and Cox uni- and multivariate analyses. Patients with high STK1p values (≥2.0 pM) 3–6 months after surgery exhibited a positive correlation to clinical stage, tumor size, occurrence of metastasis and survival. The hazard risk for the development of metastatic disease and mortality among breast cancer patients was 11–12 times higher in patients with high compared to those with low STK1p values (<2.0 pM). Notably, patients with stage III/IV disease and low STK1p values exhibited statistically significantly improved survival compared to patients with high STK1p values. A multivariate Cox analysis demonstrated that the STK1p levels 6 months after surgery was the only independent prognostic factor for metastasis and survival. In conclusion, STK1p is a prognostic marker in patients with locally advanced breast cancer and it may help identify a subgroup of stage III/IV patients with improved cancer-free survival expectancy, enabling personalized treatment. PMID:24649267

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

PubMed

Tay, Kae Jack; Polascik, Thomas J; Elshafei, Ahmed; Cher, Michael L; Given, Robert W; Mouraviev, Vladimir; Ross, Ashley E; Jones, J Stephen

2016-01-01

To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

Mutations in TP53 are a prognostic factor in colorectal hepatic metastases undergoing surgical resection.

PubMed

Molleví, David G; Serrano, Teresa; Ginestà, Mireia M; Valls, Joan; Torras, Jaume; Navarro, Matilde; Ramos, Emilio; Germà, Josep R; Jaurrieta, Eduardo; Moreno, Víctor; Figueras, Joan; Capellà, Gabriel; Villanueva, Alberto

2007-06-01

The aim of this study was to analyze the prognostic value of TP53 mutations in a consecutive series of patients with hepatic metastases (HMs) from colorectal cancer undergoing surgical resection. Ninety-one patients with liver metastases from colorectal carcinoma were included. Mutational analysis of TP53, exons 4-10, was performed by single-strand conformation polymorphism and sequencing. P53 and P21 protein immunostaining was assessed. Multivariate Cox models were adjusted for gender, number of metastasis, resection margin, presence of TP53 mutations and chemotherapy treatment. Forty-six of 91 (50.05%) metastases showed mutations in TP53, observed mainly in exons 5-8, although 14.3% (n = 13) were located in exons 9 and 10. Forty percent (n = 22) were protein-truncating mutations. TP53 status associated with multiple (> or =3) metastases (65.6%, P = 0.033), advanced primary tumor Dukes' stage (P = 0.011) and younger age (<57 years old, P = 0.03). Presence of mutation associated with poor prognosis in univariate (P = 0.017) and multivariate Cox model [hazard ratio (HR) = 1.80, 95% confidence interval (CI) = 1.07-3.06, P = 0.028]. Prognostic value was maintained in patients undergoing radical resection (R0 series, n = 79, P = 0.014). Mutation associated with a worse outcome in chemotherapy-treated patients (HR = 2.54, 95% CI = 1.12-5.75, P = 0.026). The combination of > or =3 metastases and TP53 mutation identified a subset of patients with very poor prognosis (P = 0.009). P53 and P21 protein immunostaining did not show correlation with survival. TP53 mutational status seems to be an important prognostic factor in patients undergoing surgical resection of colorectal cancer HMs.

Development and validation of a prognostic nomogram for terminally ill cancer patients.

PubMed

Feliu, Jaime; Jiménez-Gordo, Ana María; Madero, Rosario; Rodríguez-Aizcorbe, José Ramón; Espinosa, Enrique; Castro, Javier; Acedo, Jesús Domingo; Martínez, Beatriz; Alonso-Babarro, Alberto; Molina, Raquel; Cámara, Juan Carlos; García-Paredes, María Luisa; González-Barón, Manuel

2011-11-02

Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease. From February 1, 2003, to December 31, 2005, 406 consecutive terminally ill patients were entered into the study. We analyzed 38 features prognostic of life expectancy among terminally ill patients by multivariable Cox regression and identified the most accurate and parsimonious model by backward variable elimination according to the Akaike information criterion. Five clinical and laboratory variables were built into a nomogram to estimate the probability of patient survival at 15, 30, and 60 days. We validated and calibrated the nomogram with an external validation cohort of 474 patients who were treated from June 1, 2006, through December 31, 2007. The median overall survival was 29.1 days for the training set and 18.3 days for the validation set. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, lymphocyte levels, albumin levels, and time from initial diagnosis to diagnosis of terminal disease were retained in the multivariable Cox proportional hazards model as independent prognostic factors of survival and formed the basis of the nomogram. The nomogram had high predictive performance, with a bootstrapped corrected concordance index of 0.70, and it showed good calibration. External independent validation revealed 68% predictive accuracy. We developed a highly accurate tool that uses basic clinical and analytical information to predict the probability of survival at 15, 30, and 60 days in terminally ill cancer patients. This tool can help physicians making decisions on clinical care at the end of life.

High versus low-dose rate brachytherapy for cervical cancer.

PubMed

Patankar, Sonali S; Tergas, Ana I; Deutsch, Israel; Burke, William M; Hou, June Y; Ananth, Cande V; Huang, Yongmei; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

2015-03-01

Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. Women with stages IB2-IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003-2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (P<0.0001). In a multivariable model, year of diagnosis was the strongest predictor of use of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

High versus Low-Dose Rate Brachytherapy for Cervical Cancer

PubMed Central

Patankar, Sonali S.; Tergas, Ana I.; Deutsch, Israel; Burke, William M.; Hou, June Y.; Ananth, Cande V.; Huang, Yongmei; Neugut, Alfred I.; Hershman, Dawn L.; Wright, Jason D.

2015-01-01

Objectives Brachytherapy plays an important role in the treatment of cervical cancer. While small trials have shown comparable survival outcomes between high (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US. We examined the utilization of HDR brachytherapy and analyzed the impact of type of brachytherapy on survival for cervical cancer. Methods Women with stage IB2–IVA cervical cancer treated with primary (external beam and brachytherapy) radiotherapy between 2003–2011 and recorded in the National Cancer Database (NCDB) were analyzed. Generalized linear mixed models and Cox proportional hazards regression were used to examine predictors of HDR brachytherapy use and the association between HDR use and survival. Results A total of 10,564 women including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (P<0.0001). In a multivariable model, year of diagnosis was the strongest predictor of use of HDR. While patients in the Northeast were more likely to receive HDR therapy, there were no other clinical or socioeconomic characteristics associated with receipt of HDR. In a multivariable Cox model, survival was similar between the HDR and LDR groups (HR=0.93; 95% 0.83–1.03). Similar findings were noted in analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no difference in survival based on type of brachytherapy for stage IIB (P=0.68), IIIB (P=0.17), or IVA (P=0.16) tumors. Conclusions The use of HDR therapy has increased rapidly. Overall survival is similar for LDR and HDR brachytherapy. PMID:25575481

Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer.

PubMed

Liang, Ya-Nan; Liu, Yu; Wang, Letian; Yao, Guodong; Li, Xiaobo; Meng, Xiangning; Wang, Fan; Li, Ming; Tong, Dandan; Geng, Jingshu

2018-06-01

Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test. Stromal Cav-1 was downregulated in 38.56% (118/306) of tumor tissues, whereas cytoplasmic EGFR and Cav-1 were overexpressed in 53.92% (165/306) and 44.12% (135/306) of breast cancer tissues, respectively. EGFR expression was positively associated with cytoplasmic Cav-1 and not associated with stromal Cav-1 expression in breast cancer samples; however, low expression of stromal Cav-1 was negatively associated with cytoplasmic Cav-1 expression in total tumor tissues, and analogous results were identified in the chemotherapy group. Multivariate Cox's proportional hazards model analysis revealed that, for patients in the estrogen receptor (ER)(+) group, the expression of stromal Cav-1 alone was a significant prognostic marker of breast cancer. However, in the chemotherapy, human epidermal growth factor receptor 2 (HER-2)(-), HER-2(+) and ER(-) groups, the use of combined markers was more effective prognostic marker. Stromal Cav-1 has a tumor suppressor function, and the combined marker stromal Cav-1/EGFR expression was identified as an improved prognostic marker in the diagnosis of breast cancer. Parenchymal expression of Cav-1 is able to promote EGFR signaling in breast cancer, potentially being required for EGFR-mediated initiation of mitosis.

Characteristics and Outcomes of Patients with Ewing Sarcoma Over 40 Years of Age at Diagnosis

PubMed Central

Karski, Erin E.; Matthay, Katherine K.; Neuhaus, John M.; Goldsby, Robert E.; DuBois, Steven G.

2012-01-01

Background The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥ 40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. Methods This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥ 40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Results Patients ≥ 40 years of age were more likely to have extra-skeletal tumors (66.1% v 31.7%; p<0.001), axial tumors (64.0% v 57.2%; p=0.01), and metastatic disease at diagnosis (35.5% v 30.0%; p=0.04) compared to younger patients. Five-year survival for those age ≥ 40 and age < 40 were 40.6% and 54.3%, respectively (p<0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63 - 2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Conclusion Patients ≥ 40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. PMID:22959474

Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis.

PubMed

Karski, Erin E; Matthay, Katherine K; Neuhaus, John M; Goldsby, Robert E; Dubois, Steven G

2013-02-01

The peak incidence of Ewing sarcoma (EWS) is in adolescence, with little known about patients who are ≥40 years at diagnosis. We describe the clinical characteristics and survival of this rare group. This retrospective cohort study utilized the Surveillance Epidemiology and End Results database. 2780 patients were identified; including 383 patients diagnosed ≥40 years. Patient characteristics between age groups were compared using chi-squared tests. Survival from diagnosis to death was estimated via Kaplan-Meier methods, compared with log-rank tests, and modeled using multivariable Cox methods. A competing risks analysis was performed to evaluate death due to cancer. Patients ≥40 years of age were more likely to have extra-skeletal tumors (66.1% vs. 31.7%; p < 0.001), axial tumors (64.0% vs. 57.2%; p = 0.01), and metastatic disease at diagnosis (35.5% vs. 30.0%; p = 0.04) compared to younger patients. Five-year survival for those age ≥40 and age <40 were 40.6% and 54.3%, respectively (p < 0.0001). A Cox multivariable model controlling for differences between groups confirmed inferior survival for older patients (hazard ratio for death of 2.04; 95% CI 1.63-2.54; p < 0.0001); though treatment data were unavailable and not controlled for in the model. A competing risks analysis confirmed increased risk of cancer-related death in older patients. Patients ≥40 years at diagnosis with EWS are more likely to have extra-skeletal tumors, metastatic disease, and axial primary tumors suggesting a difference in tumor biology. Independent of differences in these characteristics, older patients also have a lower survival rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hospital of diagnosis and probability of having surgical treatment for resectable gastric cancer.

PubMed

van Putten, M; Verhoeven, R H A; van Sandick, J W; Plukker, J T M; Lemmens, V E P P; Wijnhoven, B P L; Nieuwenhuijzen, G A P

2016-02-01

Gastric cancer surgery is increasingly being centralized in the Netherlands, whereas the diagnosis is often made in hospitals where gastric cancer surgery is not performed. The aim of this study was to assess whether hospital of diagnosis affects the probability of undergoing surgery and its impact on overall survival. All patients with potentially curable gastric cancer according to stage (cT1/1b-4a, cN0-2, cM0) diagnosed between 2005 and 2013 were selected from The Netherlands Cancer Registry. Multilevel logistic regression was used to examine the probability of undergoing surgery according to hospital of diagnosis. The effect of variation in probability of undergoing surgery among hospitals of diagnosis on overall survival during the intervals 2005-2009 and 2010-2013 was examined by using Cox regression analysis. A total of 5620 patients with potentially curable gastric cancer, diagnosed in 91 hospitals, were included. The proportion of patients who underwent surgery ranged from 53.1 to 83.9 per cent according to hospital of diagnosis (P < 0.001); after multivariable adjustment for patient and tumour characteristics it ranged from 57.0 to 78.2 per cent (P < 0.001). Multivariable Cox regression showed that patients diagnosed between 2010 and 2013 in hospitals with a low probability of patients undergoing curative treatment had worse overall survival (hazard ratio 1.21; P < 0.001). The large variation in probability of receiving surgery for gastric cancer between hospitals of diagnosis and its impact on overall survival indicates that gastric cancer decision-making is suboptimal. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

PubMed Central

Li, Yong-Jiang; Yang, Xi; Zhang, Wen-Biao; Yi, Cheng; Wang, Feng; Li, Ping

2017-01-01

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. PMID:29033609

The Association between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and All-Cause Mortality in Acute Coronary Syndrome after Coronary Revascularization

PubMed Central

Wan, Ke; Zhao, Jianxun; Huang, Hao; Zhang, Qing; Chen, Xi; Zeng, Zhi; Zhang, Li; Chen, Yucheng

2015-01-01

Aims High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS). Methods Fasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor. Results The subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs. Conclusion The TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events. PMID:25880982

Markers of vitamin B6 status and metabolism as predictors of incident cancer: the Hordaland Health Study.

PubMed

Zuo, Hui; Ueland, Per M; Eussen, Simone J P M; Tell, Grethe S; Vollset, Stein E; Nygård, Ottar; Midttun, Øivind; Meyer, Klaus; Ulvik, Arve

2015-06-15

Dietary intake and/or circulating concentrations of vitamin B6 have been associated with risk of cancer, but results are inconsistent and mechanisms uncertain. Pyridoxal 5'-phosphate (PLP) is the most commonly used marker of B6 status. We recently proposed the ratio 3-hydroxykynurenine/xanthurenic acid (HK/XA) as an indicator of functional vitamin B6 status, and the 4-pyridoxic acid (PA) /(pyridoxal (PL) +PLP) ratio (PAr) as a marker of vitamin B6 catabolism during inflammation. We compared plasma PLP, HK/XA and PAr as predictors of cancer incidence in a prospective community-based cohort in Norway. This study included 6,539 adults without known cancer at baseline (1998-99) from the Hordaland Health Study (HUSK). HR and 95% CI were calculated for the risk of overall and site-specific cancers using multivariate Cox proportional hazards regression with adjustment for potential confounders. After a median follow-up time of 11.9 years, 963 cancer cases (501 men and 462 women) were identified. Multivariate-adjusted Cox-regression showed no significant relation of plasma PLP or HK/XA with risk of incident cancer. In contrast, PAr was significantly associated with risk of cancer with HR (95% CI) = 1.31 (1.12-1.52) per two standard deviation (SD) increment (p < 0.01). Further analysis showed that PAr was a particular strong predictor of lung cancer with HR (95% CI) = 2.46 (1.49-4.05) per two SD increment (p < 0.01). The present results indicate that associations of vitamin B6 with cancer may be related to increased catabolism of vitamin B6, in particular for lung cancer where inflammation may be largely involved in carcinogenesis. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Predictors of running-related injuries in novice runners enrolled in a systematic training program: a prospective cohort study.

PubMed

Buist, Ida; Bredeweg, Steef W; Lemmink, Koen A P M; van Mechelen, Willem; Diercks, Ron L

2010-02-01

The popularity of running is still growing. As participation increases, running-related injuries also increase. Until now, little is known about the predictors for injuries in novice runners. Predictors for running-related injuries (RRIs) will differ between male and female novice runners. Cohort study; Level of evidence, 2. Participants were 532 novice runners (226 men, 306 women) preparing for a recreational 4-mile (6.7-km) running event. After completing a baseline questionnaire and undergoing an orthopaedic examination, they were followed during the training period of 13 weeks. An RRI was defined as any self-reported running-related musculoskeletal pain of the lower extremity or back causing a restriction of running for at least 1 week. Twenty-one percent of the novice runners had at least one RRI during follow-up. The multivariate adjusted Cox regression model for male participants showed that body mass index (BMI) (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.05-1.26), previous injury in the past year (HR, 2.7; 95% CI, 1.36-5.55), and previous participation in sports without axial load (HR, 2.05; 95% CI, 1.03-4.11) were associated with RRI. In female participants, only navicular drop (HR, 0.85; 95% CI, 0.75-0.97) remained a significant predictor for RRI in the multivariate Cox regression modeling. Type A behavior and range of motion (ROM) of the hip and ankle did not affect risk. Male and female novice runners have different risk profiles. Higher BMI, previous injury, and previous sports participation without axial loading are important predictors for RRI in male participants. Further research is needed to detect more predictors for female novice runners.

The incidence and prevalence of pterygium in South Korea: A 10-year population-based Korean cohort study.

PubMed

Rim, Tyler Hyungtaek; Kang, Min Jae; Choi, Moonjung; Seo, Kyoung Yul; Kim, Sung Soo

2017-01-01

Although numerous population-based studies have reported the prevalences and risk factors for pterygium, information regarding the incidence of pterygium is scarce. This population-based cohort study aimed to evaluate the South Korean incidence and prevalence of pterygium. We retrospectively obtained data from a nationally representative sample of 1,116,364 South Koreans in the Korea National Health Insurance Service National Sample Cohort (NHIS-NSC). The associated sociodemographic factors were evaluated using multivariable Cox regression analysis, and the hazard ratios and confidence intervals were calculated. Pterygium was defined based on the Korean Classification of Diseases code, and surgically removed pterygium was defined as cases that required surgical removal. We identified 21,465 pterygium cases and 8,338 surgically removed pterygium cases during the study period. The overall incidences were 2.1 per 1,000 person-years for pterygium and 0.8 per 1,000 person-years for surgically removed pterygium. Among subjects who were ≥40 years old, the incidences were 4.3 per 1,000 person-years for pterygium and 1.7 per 1,000 person-years for surgically removed pterygium. The overall prevalences were 1.9% for pterygium and 0.6% for surgically removed pterygium, and the prevalences increased to 3.8% for pterygium and 1.4% for surgically removed pterygium among subjects who were ≥40 years old. The incidences of pterygium decreased according to year. The incidence and prevalence of pterygium were highest among 60-79-year-old individuals. Increasing age, female sex, and living in a relatively rural area were associated with increased risks of pterygium and surgically removed pterygium in the multivariable Cox regression analysis. Our analyses of South Korean national insurance claims data revealed a decreasing trend in the incidence of pterygium during the study period.

Associations of Dietary Long-Chain ω-3 Polyunsaturated Fatty Acids and Fish Consumption With Endometrial Cancer Risk in the Black Women's Health Study

PubMed Central

Brasky, Theodore M.; Sponholtz, Todd R.; Palmer, Julie R.; Rosenberg, Lynn; Ruiz-Narváez, Edward A.; Wise, Lauren A.

2016-01-01

Dietary long-chain (LC) ω-3 polyunsaturated fatty acids (PUFAs), which derive primarily from intakes of fatty fish, are thought to inhibit inflammation and de novo estrogen synthesis. This study prospectively examined the associations of dietary LC ω-3 PUFAs and fish with endometrial cancer risk in 47,602 African-American women living in the United States, aged 21–69 years at baseline in 1995, and followed them until 2013 (n = 282 cases). Multivariable-adjusted Cox regression models estimated hazard ratios and 95% confidence intervals for associations of LC ω-3 PUFA (quintiled) and fish (quartiled) intake with endometrial cancer risk, overall and by body mass index (BMI; weight (kg)/height (m)2). The hazard ratio for quintile 5 of total dietary LC ω-3 PUFAs versus quintile 1 was 0.79 (95% confidence interval (CI): 0.51, 1.24); there was no linear trend. Hazard ratios for the association were smaller among normal-weight women (BMI <25: hazard ratio (HR) = 0.53, 95% CI: 0.18, 1.58) than among overweight/obese women (BMI ≥25: HR = 0.88, 95% CI: 0.54, 1.43), but these differences were not statistically significant. Fish intake was also not associated with risk (quartile 4 vs. quartile 1: HR = 0.86, 95% CI: 0.56, 1.31). Again hazard ratios were smaller among normal-weight women (HR = 0.65) than among overweight/obese women (HR = 0.94). While compatible with no association, the hazard ratios observed among leaner African-American women are similar to those from recent prospective studies conducted in predominantly white populations. PMID:26755676

Medication for Alzheimer's disease and associated fall hazard: a retrospective cohort study from the Alzheimer's Disease Neuroimaging Initiative.

PubMed

Epstein, Noam U; Guo, Rong; Farlow, Martin R; Singh, Jaswinder P; Fisher, Morris

2014-02-01

Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications, which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer's disease (AD) patients and association with falls is limited. We examined the association between falls and medication use in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in the ADNI, including healthy controls and subjects with mild cognitive impairment or Alzheimer's. Reports detailing adverse event falls were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of the first fall. Age (p < 0.0001), Functional Activities Questionnaire (p = 0.035), Beers List (p = 0.0477) and medications for treating cognitive symptoms of Alzheimer's (p = 0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer's medication use (p = 0.0005) was associated with hazard of fall. Medication was changed by the clinician after an adverse fall event in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. We found a significant association between the use of symptomatic medication treating cognitive symptoms in AD and hazard of fall after adjusting for age and Beers List medication use. Additional pharmacovigilance of the association between falls and Alzheimer's medication use is warranted.

Medication for Alzheimer’s Disease and Associated Fall Hazard: a Retrospective Cohort Study from the Alzheimer’s Disease Neuro-Imaging Initiative

PubMed Central

Epstein, Noam U.; Guo, Rong; Farlow, Martin R.; Singh, Jaswinder P.; Fisher, Morris

2014-01-01

Background Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer’s patients and association with falls is limited. Objective We examined the association between falls and medication use in the Alzheimer’s Disease Neuro-Imaging Initiative (ADNI). Methods Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in ADNI including healthy controls and subjects with mild cognitive impairment or Alzheimer’s. Adverse event fall reports were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of first fall. Results Age (p<0.0001), functional activities questionnaire (p=0.035), Beers list (p=0.0477) and medications for treating cognitive symptoms of Alzheimer’s (p=0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer’s medication use (p=0.0005) was associated with hazard of fall. Medication was changed after an adverse fall event by the clinician in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. Conclusion We found a significant association between use of symptomatic medication treating cognitive symptoms in Alzheimer’s disease and hazard of fall after adjusting for age and Beers list medication use. Additional pharmaco-vigilance of the association between falls and Alzheimer’s medication use is warranted. PMID:24357133

Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study.

PubMed

Ren, J S; Freedman, N D; Kamangar, F; Dawsey, S M; Hollenbeck, A R; Schatzkin, A; Abnet, C C

2010-07-01

The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric non-cardia cancer, 123 Oesophageal Squamous Cell Carcinoma (ESCC) and 305 Oesophageal Adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of > or =1 cup/day was 0.37 (95% CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95% CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last 3 years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95% CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods. Published by Elsevier Ltd.

Tea, coffee, carbonated soft drinks and upper gastrointestinal tract cancer risk in a large United States prospective cohort study

PubMed Central

Ren, JS; Freedman, ND; Kamangar, F; Dawsey, SM; Hollenbeck, AR; Schatzkin, A; Abnet, CC

2010-01-01

The authors investigated the relationship between hot tea, iced tea, coffee and carbonated soft drinks consumption and upper gastrointestinal tract cancers risk in the NIH-AARP Study. During 2,584,953 person-years of follow-up on 481,563 subjects, 392 oral cavity, 178 pharynx, 307 larynx, 231 gastric cardia, 224 gastric noncardia cancer, 123 esophageal squamous cell carcinoma (ESCC) and 305 esophageal adenocarcinoma (EADC) cases were accrued. Hazard ratios (HRs) and 95% Confidence Intervals (95%CIs) were calculated by multivariate-adjusted Cox regression. Compared to non-drinking, the hazard ratio for hot tea intake of ≥1 cup/day was 0.37 (95%CI: 0.20, 0.70) for pharyngeal cancer. The authors also observed a significant association between coffee drinking and risk of gastric cardia cancer (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 1.57 (95%CI: 1.03, 2.39)), and an inverse association between coffee drinking and EADC for the cases occurring in the last three years of follow-up (compared to <1 cup/day, the hazard ratio for drinking >3 cups/day was 0.54 (95%CI: 0.31, 0.92)), but no association in earlier follow-up. In summary, hot tea intake was inversely associated with pharyngeal cancer, and coffee was directly associated with gastric cardia cancer, but was inversely associated with EADC during some follow-up periods. PMID:20395127

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer.

PubMed

Gagnon, B; Abrahamowicz, M; Xiao, Y; Beauchamp, M-E; MacDonald, N; Kasymjanova, G; Kreisman, H; Small, D

2010-03-30

C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03-1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.

Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

PubMed

Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

2013-01-01

In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

Transition from a multiport technique to a single-port technique for lung cancer surgery: is lymph node dissection inferior using the single-port technique?†.

PubMed

Liu, Chia-Chuan; Shih, Chih-Shiun; Pennarun, Nicolas; Cheng, Chih-Tao

2016-01-01

The feasibility and radicalism of lymph node dissection for lung cancer surgery by a single-port technique has frequently been challenged. We performed a retrospective cohort study to investigate this issue. Two chest surgeons initiated multiple-port thoracoscopic surgery in a 180-bed cancer centre in 2005 and shifted to a single-port technique gradually after 2010. Data, including demographic and clinical information, from 389 patients receiving multiport thoracoscopic lobectomy or segmentectomy and 149 consecutive patients undergoing either single-port lobectomy or segmentectomy for primary non-small-cell lung cancer were retrieved and entered for statistical analysis by multivariable linear regression models and Box-Cox transformed multivariable analysis. The mean number of total dissected lymph nodes in the lobectomy group was 28.5 ± 11.7 for the single-port group versus 25.2 ± 11.3 for the multiport group; the mean number of total dissected lymph nodes in the segmentectomy group was 19.5 ± 10.8 for the single-port group versus 17.9 ± 10.3 for the multiport group. In linear multivariable and after Box-Cox transformed multivariable analyses, the single-port approach was still associated with a higher total number of dissected lymph nodes. The total number of dissected lymph nodes for primary lung cancer surgery by single-port video-assisted thoracoscopic surgery (VATS) was higher than by multiport VATS in univariable, multivariable linear regression and Box-Cox transformed multivariable analyses. This study confirmed that highly effective lymph node dissection could be achieved through single-port VATS in our setting. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Application of multivariate Gaussian detection theory to known non-Gaussian probability density functions

NASA Astrophysics Data System (ADS)

Schwartz, Craig R.; Thelen, Brian J.; Kenton, Arthur C.

1995-06-01

A statistical parametric multispectral sensor performance model was developed by ERIM to support mine field detection studies, multispectral sensor design/performance trade-off studies, and target detection algorithm development. The model assumes target detection algorithms and their performance models which are based on data assumed to obey multivariate Gaussian probability distribution functions (PDFs). The applicability of these algorithms and performance models can be generalized to data having non-Gaussian PDFs through the use of transforms which convert non-Gaussian data to Gaussian (or near-Gaussian) data. An example of one such transform is the Box-Cox power law transform. In practice, such a transform can be applied to non-Gaussian data prior to the introduction of a detection algorithm that is formally based on the assumption of multivariate Gaussian data. This paper presents an extension of these techniques to the case where the joint multivariate probability density function of the non-Gaussian input data is known, and where the joint estimate of the multivariate Gaussian statistics, under the Box-Cox transform, is desired. The jointly estimated multivariate Gaussian statistics can then be used to predict the performance of a target detection algorithm which has an associated Gaussian performance model.

Coffee, caffeine, and risk of completed suicide: results from three prospective cohorts of American adults.

PubMed

Lucas, Michel; O'Reilly, Eilis J; Pan, An; Mirzaei, Fariba; Willett, Walter C; Okereke, Olivia I; Ascherio, Alberto

2014-07-01

To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of US men and women. We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988-2008), 73,820 women in the Nurses' Health Study (NHS, 1992-2008), and 91,005 women in the NHS II (1993-2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every 4 years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. We documented 277 deaths from suicide. Compared to those consuming ≤ 1 cup/week of caffeinated coffee (< 8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38-0.78) for those consuming 2-3 cups/day and 0.47 (0.27-0.81) for those consuming ≥ 4 cups/day (P trend < 0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63-0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63-0.93) for each increment of 300 mg/day of caffeine. These results from three large cohorts support an association between caffeine consumption and lower risk of suicide.

Effect of late HIV diagnosis on HIV-related mortality among adults in general hospitals of Central Zone Tigray, northern Ethiopia: a retrospective cohort study.

PubMed

Belay, Hadera; Alemseged, Fessahaye; Angesom, Teklit; Hintsa, Solomon; Abay, Mebrahtu

2017-01-01

The global incidence of HIV infection is not significantly decreasing, especially in sub-Saharan African countries, including Ethiopia. Though there is availability and accessibility of free HIV services, people are not being diagnosed early for HIV, and hence patients are still dying of HIV-related causes. This research is aimed at verifying the effect of late diagnosis of HIV on HIV-related mortality in Central Zone Tigray, Ethiopia. A retrospective cohort study among adult (≥15 years old) HIV patients in three general hospitals of Tigray was conducted. Record reviews were carried out retrospectively from 2010 to 2015. Sample size was determined using stpower Cox in Stata software. Data were entered into EpiData version 3.1 software and transferred to Stata version 12 for analysis. Both bivariable and multivariable analyses were performed using Cox regression model to compare the HIV-related mortality of exposed (cluster of differentiation 4 cells count <350 cells/mm 3 ) and nonexposed (≥350 cells/mm 3 ) patients using adjusted hazard ratio (AHR) at 95% confidence interval (CI). In all, 638 HIV patients were analyzed, contributing 2,105.6 person-years. Forty-eight (7.5%) patients died of HIV-related causes with a mortality rate of 2.28 per 100 person-years. In the multivariable Cox regression model, patients with late diagnosis of HIV had a higher risk of mortality (AHR =3.22, 95% CI: 1.17-8.82) than patients with early diagnosis of HIV. Rural residence (AHR =1.96, 95% CI: 1.05-3.68), unemployment (AHR =2.70, 95% CI: 1.03-7.08), bedridden patients (AHR =2.98, 95% CI: 1.45-6.13), ambulatory patients (AHR =2.54, 95% CI: 1.05-6.15), and baseline hemoglobin level of <11 mg/dL (AHR =3.06, 95% CI: 1.51-6.23) were other independent predictors of mortality. Late diagnosis of HIV increased HIV-related mortality. Rural residence, unemployment, bedridden and ambulatory patients, and baseline hemoglobin level <11 mg/dL were also independent predictors of HIV-related mortality.

Impact of hemodialysis dose and frequency on survival of patients on chronic hemodialysis in Lithuania during 1998-2005.

PubMed

Stankuvienė, Asta; Ziginskienė, Edita; Kuzminskis, Vytautas; Bumblytė, Inga Arūnė

2010-01-01

The question of the targets of dialysis dosing remains controversial since the beginning of the long-term dialysis treatment era. It is still uncertain if higher dialysis dose is better. The aim of our study was to investigate issues of dialysis dose in Lithuania during the period of 1998-2005 and to determine associations between hemodialysis dose and survival of patients on chronic hemodialysis. We analyzed data of all patients who started hemodialysis due to end-stage renal disease in Lithuania between January 1, 1998, and December 31, 2005. The information about hemodialysis frequency, duration, and adequacy (according to Kt/V) was obtained from medical documentation. The overall survival rate was estimated using the Kaplan-Meier method. Survival comparisons were made using the log-rank or Breslow tests. Univariate Cox proportional hazards analysis was used to select variables significantly associated with the risk of death; then these variables were included in multivariate Cox proportional hazards models. During the study period, from 2428 patients who started chronic hemodialysis, 58.5% of patients started hemodialysis three times a week. More than one-third (36.2%) of patients were dialyzed twice weekly, and 5.3% of patients started hemodialysis once weekly. Survival analysis revealed that patients dialyzed less than three times per week survived shorter than patients receiving a higher dialysis dose. Duration of HD session of ≤8 hours per week was an independent risk factor for mortality. A higher mean Kt/V was associated with better survival of patients on chronic hemodialysis. Dialysis frequency and weekly duration of HD sessions were dependent on HD accessibility in Lithuania during the period of 1998-2005. Better survival of patients on chronic hemodialysis was associated with a higher hemodialysis dose.

An integrated mRNA and microRNA expression signature for glioblastoma multiforme prognosis.

PubMed

Xiong, Jie; Bing, Zhitong; Su, Yanlin; Deng, Defeng; Peng, Xiaoning

2014-01-01

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures.

Is Functional Independence Associated With Improved Long-Term Survival After Lung Transplantation?

PubMed

Osho, Asishana; Mulvihill, Michael; Lamba, Nayan; Hirji, Sameer; Yerokun, Babatunde; Bishawi, Muath; Spencer, Philip; Panda, Nikhil; Villavicencio, Mauricio; Hartwig, Matthew

2018-07-01

Existing research demonstrates superior short-term outcomes (length of stay, 1-year survival) after lung transplantation in patients with preoperative functional independence. The aim of this study was to determine whether advantages remain significant in the long-term. The United Network for Organ Sharing database was queried for adult, first-time, isolated lung transplantation records from January 2005 to December 2015. Stratification was performed based on Karnofsky Performance Status Score (3 groups) and on employment at the time of transplantation (2 groups). Kaplan-Meier and Cox analyses were performed to determine the association between these factors and survival in the long-term. Of 16,497 patients meeting criteria, 1,581 (9.6%) were almost completely independent at the time of transplant vs 5,662 (34.3%) who were disabled (completely reliant on others for activities of daily living). Cox models adjusting for recipient, donor, and transplant factors demonstrated a statistically significant association between disability at the time of transplant and long-term death (hazard ratio, 1.26; 95% confidence interval, 1.14 to 1.40; p < 0.001). There were 15,931 patients with available data on paid employment at the time of transplantation. Multivariable analysis demonstrated a statistically significant association between employment at the time of transplantation and death (hazard ratio, 0.86; 95% confidence interval, 0.75 to 0.91; p < 0.001). Preoperative functional independence and maintenance of employment are associated with superior long-term outcomes in lung recipients. The results highlight potential benefits of pretransplant functional rehabilitation for patients on the waiting list for lungs. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The impact of high serum bicarbonate levels on mortality in hemodialysis patients.

PubMed

Chang, Kyung Yoon; Kim, Hyung Wook; Kim, Woo Jeong; Kim, Yong Kyun; Kim, Su-Hyun; Song, Ho Chul; Kim, Young Ok; Jin, Dong Chan; Choi, Euy Jin; Yang, Chul Woo; Kim, Yong-Lim; Kim, Nam-Ho; Kang, Shin-Wook; Kim, Yon-Su; Kim, Young Soo

2017-01-01

The optimal serum bicarbonate level is controversial for patients who are undergoing hemodialysis (HD). In this study, we analyzed the impact of serum bicarbonate levels on mortality among HD patients. Prevalent HD patients were selected from the Clinical Research Center registry for End Stage Renal Disease cohort in Korea. Patients were categorized into quartiles according to their total carbon dioxide (tCO 2 ) levels: quartile 1, a tCO 2 of < 19.4 mEq/L; quartile 2, a tCO 2 of 19.4 to 21.5 mEq/L; quartile 3, a tCO 2 of 21.6 to 23.9 mEq/L; and quartile 4, a tCO 2 of ≥ 24 mEq/L. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) and confidence interval (CI) for mortality. We included 1,159 prevalent HD patients, with a median follow-up period of 37 months. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher in patients from quartile 4, compared to those from the other quartiles ( p = 0.009, log-rank test). The multivariate Cox proportional hazard model revealed that patients from quartile 4 had significantly higher risk of mortality than those from quartile 1, 2 and 3, after adjusting for the clinical variables in model 1 (HR, 1.99; 95% CI, 1.15 to 3.45; p = 0.01) and model 2 (HR, 1.82; 95% CI, 1.03 to 3.22; p = 0.04). Our data indicate that high serum bicarbonate levels (a tCO2 of ≥ 24 mEq/L) were associated with increased mortality among prevalent HD patients. Further effort might be necessary in finding the cause and correcting metabolic alkalosis in the chronic HD patients with high serum bicarbonate levels.

An Integrated mRNA and microRNA Expression Signature for Glioblastoma Multiforme Prognosis

PubMed Central

Xiong, Jie; Bing, Zhitong; Su, Yanlin; Deng, Defeng; Peng, Xiaoning

2014-01-01

Although patients with Glioblastoma multiforme (GBM) have grave prognosis, significant variability in patient outcome is observed. The objective of this study is to identify a molecular signature for GBM prognosis. We subjected 355 mRNA and microRNA expression profiles to elastic net-regulated Cox regression for identification of an integrated RNA signature for GBM prognosis. A prognostic index (PI) was generated for patient stratification. Survival comparison was conducted by Kaplan-Meier method and a general multivariate Cox regression procedure was applied to evaluate the independence of the PI. The abilities and efficiencies of signatures to predict GBM patient outcome was assessed and compared by the area under the curve (AUC) of the receiver-operator characteristic (ROC). An integrated RNA prognostic signature consisted by 4 protective mRNAs, 12 risky mRNAs, and 1 risky microRNA was identified. Decreased survival was associated with being in the high-risk group (hazard ratio = 2.864, P<0.0001). The prognostic value of the integrated signature was validated in five independent GBM expression datasets (n = 201, hazard ratio = 2.453, P<0.0001). The PI outperformed the known clinical factors, mRNA-only, and miRNA-only prognostic signatures for GBM prognosis (area under the ROC curve for the integrated RNA, mRNA-only, and miRNA-only signatures were 0.828, 0.742, and 0.757 at 3 years of overall survival, respectively, P<0.0001 by permutation test). We describe the first, to our knowledge, robust transcriptome-based integrated RNA signature that improves the current GBM prognosis based on clinical variables, mRNA-only, and miRNA-only signatures. PMID:24871302

Clinical Prognosis of Superior Versus Basal Segment Stage I Non-Small Cell Lung Cancer.

PubMed

Handa, Yoshinori; Tsutani, Yasuhiro; Tsubokawa, Norifumi; Misumi, Keizo; Hanaki, Hideaki; Miyata, Yoshihiro; Okada, Morihito

2017-12-01

Despite its extensive size, variations in the clinicopathologic features of tumors in the lower lobe have been little studied. The present study investigated the prognostic differences in tumors originating from the superior and basal segments of the lower lobe in patients with non-small cell lung cancer. Data of 134 patients who underwent lobectomy or segmentectomy with systematic nodal dissection for clinical stage I, radiologically solid-dominant, non-small cell lung cancer in the superior segment (n = 60) or basal segment (n = 74) between April 2007 and December 2015 were retrospectively reviewed. Factors affecting survival were assessed by the Kaplan-Meier method and Cox regression analyses. Prognosis in the superior segment group was worse than that in the basal segment group (5-year overall survival rates 62.6% versus 89.9%, p = 0.0072; and 5-year recurrence-free survival rates 54.4% versus 75.7%, p = 0.032). In multivariable Cox regression analysis, a superior segment tumor was an independent factor for poor overall survival (hazard ratio 3.33, 95% confidence interval: 1.22 to 13.5, p = 0.010) and recurrence-free survival (hazard ratio 2.90, 95% confidence interval: 1.20 to 7.00, p = 0.008). The superior segment group tended to have more pathologic mediastinal lymph node metastases than the basal segment group (15.0% versus 5.4%, p = 0.080). Tumor location was a prognostic factor for clinical stage I non-small cell lung cancer in the lower lobe. Patients with superior segment tumors had worse prognosis than patients with basal segment tumors, with more metastases in mediastinal lymph nodes. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

PubMed

Rath, T J; Narayanan, S; Hughes, M A; Ferris, R L; Chiosea, S I; Branstetter, B F

2017-07-01

Human papillomavirus-related oropharyngeal squamous cell carcinoma is associated with cystic lymph nodes on CT and has a favorable prognosis. A subset of patients with aggressive disease experience treatment failure. Our aim was to determine whether the extent of cystic lymph node burden on staging CT can serve as an imaging biomarker to predict treatment failure in human papillomavirus-related oropharyngeal squamous cell carcinoma. We identified patients with human papilloma virus-related oropharyngeal squamous cell carcinoma and staging neck CTs. Demographic and clinical variables were recorded. We retrospectively classified the metastatic lymph node burden on CT as cystic or solid and assessed radiologic extracapsular spread. Biopsy, subsequent imaging, or clinical follow-up was the reference standard for treatment failure. The primary end point was disease-free survival. Cox proportional hazard regression analyses of clinical, demographic, and anatomic variables for treatment failure were performed. One hundred eighty-three patients were included with a mean follow-up of 38 months. In univariate analysis, the following variables had a statistically significant association with treatment failure: solid-versus-cystic lymph nodes, clinical T-stage, clinical N-stage, and radiologic evidence of extracapsular spread. The multivariate Cox proportional hazard model resulted in a model that included solid-versus-cystic lymph nodes, T-stage, and radiologic evidence of extracapsular spread as independent predictors of treatment failure. Patients with cystic nodal metastasis at staging had significantly better disease-free survival than patients with solid lymph nodes. In human papilloma virus-related oropharyngeal squamous cell carcinoma, patients with solid lymph node metastases are at higher risk for treatment failure with worse disease-free survival. Solid lymph nodes may serve as an imaging biomarker to tailor individual treatment regimens. © 2017 by American Journal of Neuroradiology.

Worsening renal function is not associated with response to treatment in acute heart failure

PubMed Central

Ather, Sameer; Bavishi, Chirag; McCauley, Mark D; Dhaliwal, Amandeep; Deswal, Anita; Johnson, Sarah; Chan, Wenyaw; Aguilar, David; Pritchett, Allison M; Ramasubbu, Kumudha; Wehrens, Xander HT; Bozkurt, Biykem

2015-01-01

Background About a fourth of acute decompensated heart failure (ADHF) patients develop renal dysfunction during their admission. To date, the association of ADHF treatment with the development of worsening renal function (WRF) remains contentious. Thus, we examined the association of WRF with changes in BNP levels and with mortality. Methods We performed retrospective chart review of patients admitted with ADHF who had BNP, eGFR, creatinine and blood urea nitrogen (BUN) values measured both on admission and discharge. Survival analysis was conducted using Cox proportional hazards model and correlation was measured using Spearman's rank correlation test. Results 358 patients admitted for ADHF were evaluated. WRF was defined as >20% reduction in eGFR from admission to discharge and response to treatment was assessed by ΔBNP. There was a statistically significant reduction in BNP and increase in BUN during the admission. ΔBNP did not correlate with either ΔGFR or ΔBUN. Patients who developed WRF and those who did not, had a similar reduction in BNP. On univariate survival analysis, ΔBUN, but not ΔeGFR, was associated with 1-year mortality. In multivariate Cox proportional hazards model, BUN at discharge was associated with 1-year mortality (HR: 1.02, p<0.001), but ΔeGFR and ΔBUN were not associated with the primary endpoint. Conclusion During ADHF treatment, ΔBNP was not associated with changes in renal function. Development of WRF during ADHF treatment was not associated with mortality. Our study suggests that development of WRF should not preclude diuresis in ADHF patients in the absence of volume depletion. PMID:22633437

Predictors of attrition from care at 2 years in a prospective cohort of HIV-infected adults in Tigray, Ethiopia

PubMed Central

Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Fucili, Luca; Gregorio, Massimiliano Di; Mirra, Marco; Castro, Paola De; Terlizzi, Roberta; Tatarelli, Paola; Binelli, Andrea; Zegeye, Teame; Campagnoli, Michela; Vella, Stefano; Abraham, Loko; Godefay, Hagos

2017-01-01

Introduction Ethiopia has experienced rapid expansion of antiretroviral therapy (ART). However, as long-term retention in ART therapy is key for ART effectiveness, determinants of attrition need to be identified so appropriate interventions can be designed. Methods We used data from the ‘Cohort of African people Starting Antiretroviral therapy’ (CASA) project, a prospective study of a cohort of HIV-infected patients who started ART in seven health facilities (HFs). We analysed the data of patients who had started first-line ART between January 2013 and December 2014. The Kaplan–Meier method was used to estimate the probability of retention at different time points. The Cox proportional hazards model was used to identify factors associated with attrition. Results A total of 1198 patients were included in the study. Kaplan–Meier estimates of retention in care were 83.9%, 82.1% and 79.8% at 12, 18 and 24 months after starting ART, respectively. Attrition was mainly due to loss to follow-up, transferred-out patients and documented mortality. A multivariate Cox proportional hazard model showed that male sex, CD4 count <200 cells/µL and the type of HF were significantly associated with attrition. Conclusions The observed attrition differences according to gender suggest that separate interventions designed for women and men should be explored. Moreover, innovative strategies to increase HIV testing should be supported to avoid CD4 levels falling too low, a factor significantly associated with higher attrition in our study. Finally, specific studies to analyse the reasons for different levels of attrition among HFs are required. PMID:29082011

Long-term return behavior of Chinese whole blood donors.

PubMed

Guo, Nan; Wang, Jingxing; Yu, Qilu; Yang, Tonghan; Dong, Xiangdong; Wen, Guoxin; Tiemuer, Mei-hei-li; Li, Julin; He, Weilan; Lv, Yunlai; Ma, Hongli; Wen, Xiuqiong; Huang, Mei; Ness, Paul; Liu, Jing; Wright, David J; Nelson, Kenrad; Shan, Hua

2013-09-01

It is important to understand donor return behavior to maintain sufficient numbers of blood donors in developing countries where blood supplies are often inadequate. A total of 54,267 whole blood (WB) donors who donated between January 1 and March 31, 2008, at the five blood centers in China were followed for 2.5 years. Logistic regression was conducted to identify factors associated with their return behavior. A recurrent-event Cox proportional-hazard model was used to evaluate the overall effect of demographic variables and return behavior among first-time donors. Donors with previous donation history were more likely to return and the number of previous returns was positively associated with future return (odds ratios, 3.31, 4.82, and 8.16 for one, two to three, and more than three times compared to none). Thirty-four percent of donors (first-time donor, 21%; repeat donor, 54%) made at least one return donation, with 14% returning in the first 9 months. The multivariable logistic regression model for all WB donors and the Cox proportional hazard model for first-time donors showed consistent predictors for return: female sex, older age (≥ 25 years), larger volume (300 or 400 mL), and donating in satellite collection site. Encouraging first-time donors to make multiple donations is important for keeping adequate blood supply. The finding that first-time and repeat donors shared the same predictors for return indicates that retention strategies on repeat donors may be effective on first-time donors. Studies on motivators and barriers to return are needed, so that successful retention strategies can be tailored. © 2013 American Association of Blood Banks.

Association between implementation of a code stroke system and poststroke epilepsy.

PubMed

Chen, Ziyi; Churilov, Leonid; Chen, Ziyuan; Naylor, Jillian; Koome, Miriam; Yan, Bernard; Kwan, Patrick

2018-03-27

We aimed to investigate the effect of a code stroke system on the development of poststroke epilepsy. We retrospectively analyzed consecutive patients treated with IV thrombolysis under or outside the code stroke system between 2003 and 2012. Patients were followed up for at least 2 years or until death. Factors with p < 0.1 in univariate comparisons were selected for multivariable logistic and Cox regression. A total of 409 patients met the eligibility criteria. Their median age at stroke onset was 75 years (interquartile range 64-83 years); 220 (53.8%) were male. The median follow-up duration was 1,074 days (interquartile range 119-1,671 days). Thirty-two patients (7.8%) had poststroke seizures during follow-up, comprising 7 (1.7%) with acute symptomatic seizures and 25 (6.1%) with late-onset seizures. Twenty-six patients (6.4%) fulfilled the definition of poststroke epilepsy. Three hundred eighteen patients (77.8%) were treated with the code stroke system while 91 (22.2%) were not. After adjustment for age and stroke etiology, use of the code stroke system was associated with decreased odds of poststroke epilepsy (odds ratio = 0.36, 95% confidence interval 0.14-0.87, p = 0.024). Cox regression showed lower adjusted hazard rates for poststroke epilepsy within 5 years for patients managed under the code stroke system (hazard ratio = 0.60, 95% confidence interval 0.47-0.79, p < 0.001). The code stroke system was associated with reduced odds and instantaneous risk of poststroke epilepsy. Further studies are required to identify the contribution of the individual components and mechanisms against epileptogenesis after stroke. This study provides Class III evidence that for people with acute ischemic stroke, implementation of a code stroke system reduces the risk of poststroke epilepsy. © 2018 American Academy of Neurology.

Impact of neonatal intensive care bed configuration on rates of late-onset bacterial sepsis and methicillin-resistant Staphylococcus aureus colonization

PubMed Central

Julian, Samuel; Burnham, Carey-Ann D.; Sellenriek, Patricia; Shannon, William D.; Hamvas, Aaron; Tarr, Phillip I.; Warner, Barbara B.

2016-01-01

Objectives Infections cause significant morbidity and mortality in neonatal intensive care units (NICUs). The association between nursery design and nosocomial infections has not been delineated. We hypothesized that rates of colonization by methicillin-resistant Staphylococcus aureus (MRSA), late-onset sepsis, and mortality are reduced in single-patient rooms. Design Retrospective cohort study. Setting NICU in a tertiary referral center. Methods Our NICU is organized into single-patient and open-unit rooms. Clinical datasets including bed location and microbiology results were examined over a 29-month period. Differences in outcomes between bed configurations were determined by Chi-square and Cox regression. Patients All NICU patients. Results Among 1823 patients representing 55,166 patient-days, single-patient and open-unit models had similar incidences of MRSA colonization and MRSA colonization-free survival times. Average daily census was associated with MRSA colonization rates only in single-patient rooms (hazard ratio 1.31, p=0.039), while hand hygiene compliance on room entry and exit was associated with lower colonization rates independent of bed configuration (hazard ratios 0.834 and 0.719 per 1% higher compliance, respectively). Late-onset sepsis rates were similar in single-patient and open-unit models as were sepsis-free survival and the combined outcome of sepsis or death. After controlling for demographic, clinical and unit-based variables, multivariate Cox regression demonstrated that bed configuration had no effect on MRSA colonization, late-onset sepsis, or mortality. Conclusions MRSA colonization rate was impacted by hand hygiene compliance, regardless of room configuration, while average daily census only affected infants in single-patient rooms. Single-patient rooms did not reduce the rates of MRSA colonization, late-onset sepsis or death. PMID:26108888

A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival

PubMed Central

Graham, C.; Orr, C.; Bricks, C.S.; Hopman, W.M.; Hammad, N.; Ramjeesingh, R.

2016-01-01

Background Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. Methods We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan–Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). Results We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). Conclusions Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses. PMID:28050148

Drugs for metabolic conditions and prostate cancer death in men on GnRH agonists.

PubMed

Bosco, Cecilia; Wong, Chloe; Garmo, Hans; Crawley, Danielle; Holmberg, Lars; Hammar, Niklas; Adolfsson, Jan; Stattin, Pär; Van Hemelrijck, Mieke

2018-02-01

To evaluate whether drugs for metabolic conditions influence prostate cancer-specific mortality in men starting gonadotrophin-releasing hormone (GnRH) agonists, as it is unclear whether metabolic syndrome and its related drugs is affecting treatment response in men with prostate cancer on GnRH agonists. We selected all men receiving GnRH agonists as primary treatment in the Prostate Cancer data Base Sweden (PCBaSe) (n = 9267). Use of drugs for metabolic conditions (i.e. anti-diabetes, anti-dyslipidaemia, and antihypertension) in relation to all-cause, cardiovascular disease (CVD), and prostate cancer-specific death were studied using multivariate Cox proportional hazard and Fine and Gray competing regression models. In all, 6322 (68%) men used at least one drug for a metabolic condition at GnRH agonist initiation: 46% on antihypertensive drugs only, 32% on drugs for dyslipidaemia and hypertension, and ~10% on drugs for more than two metabolic conditions. Cox models indicated a weak increased risk of prostate cancer death in men who were on drugs for hypertension only (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.03-1.23) or drugs for hyperglycaemia (HR 1.19, 95% CI 1.06-1.35) at GnRH agonist initiation. However, upon taking into account competing risk from CVD death, none of the drugs for metabolic conditions were associated with an increased risk of prostate cancer death. We did not find evidence for a better or worse response to GnRH agonists in men with prostate cancer who were also on drugs for hypertension, dyslipidaemia, or hyperglycaemia. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Capillary loss on nailfold capillary microscopy is associated with mortality in systemic sclerosis.

PubMed

Pavan, Thais Rohde; Bredemeier, Markus; Hax, Vanessa; Capobianco, Karina Gatz; da Silva Mendonça Chakr, Rafael; Xavier, Ricardo Machado

2018-02-01

The objective of this study is to test the association of the severity of nailfold capillaroscopy (NFC) abnormalities with mortality in systemic sclerosis (SSc). One hundred and seventy SSc patients underwent an extensive evaluation (including high-resolution computed tomography, pulmonary function tests, and Doppler echocardiography) at baseline following a standard protocol. Capillary loss on NFC was evaluated using the avascular score (AS, ranging from 0 to 3), and the mean number of ectasias, megacapillaries, and hemorrhages per finger was also recorded. After a mean period of 10.1 ± 4.9 years, the life status of the patients was ascertained. Univariate and multivariate Cox proportional hazards models were used for statistical analysis. Overall, 73 patients died. By univariate Cox analysis, the AS was significantly associated with mortality (hazard ratio [HR] = 1.64, 95% CI 1.22 to 2.19, p = 0.001). In our study, this association was stronger than that of race, gender, anticentromere antibodies, anti-topoisomerase I antibodies, and form of disease and had similar strength to that of skin score in univariate analyses. However, after controlling for a combination of variables (age, skin score, gender, race, signs of peripheral ischemia, and extent of interstitial lung disease, all independently associated with mortality), the association of AS with mortality was blunted (HR = 1.15, 95% CI 0.80 to 1.65, p = 0.445). Other NFC variables were not related to mortality. AS was associated with higher risk of death and, despite not having an independent association with mortality after controlling for a set of demographic and clinical variables, may be a useful tool in prognostic evaluation of SSc.

SCD-HeFT: Use of RR Interval Statistics for Long-term Risk Stratification for Arrhythmic Sudden Cardiac Death

PubMed Central

Au-yeung, Wan-tai M.; Reinhall, Per; Poole, Jeanne E.; Anderson, Jill; Johnson, George; Fletcher, Ross D.; Moore, Hans J.; Mark, Daniel B.; Lee, Kerry L.; Bardy, Gust H.

2015-01-01

Background In the SCD-HeFT a significant fraction of the congestive heart failure (CHF) patients ultimately did not die suddenly from arrhythmic causes. CHF patients will benefit from better tools to identify if ICD therapy is needed. Objective To identify predictor variables from baseline SCD-HeFT patients’ RR intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test. Methods Ten predictor variables were extracted from pre-randomization Holter data from 475 patients enrolled in the SCD-HeFT ICD arm using novel and traditional heart rate variability methods. All variables were correlated to SCD using Mann Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed. Results α1 and α2 from detrended fluctuation analysis, the ratio of low to high frequency power, the number of PVCs per hour and heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (p<0.001) and survival (log-rank p<0.01). The most powerful multivariate predictor tool using the Cox Proportional Hazards was α2 with a hazard ratio of 0.0465 (95% CI: 0.00528 – 0.409, p<0.01). Conclusion Predictor variables from RR intervals correlate to the occurrences of SCD and distinguish survival among SCD-HeFT ICD patients. We believe SCD prediction models should incorporate Holter based RR interval analysis to refine ICD patient selection especially in removing patients who are unlikely to benefit from ICD therapy. PMID:26096609

Cell cycle-related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients.

PubMed

Chen, Jinyun; Pande, Mala; Huang, Yu-Jing; Wei, Chongjuan; Amos, Christopher I; Talseth-Palmer, Bente A; Meldrum, Cliff J; Chen, Wei V; Gorlov, Ivan P; Lynch, Patrick M; Scott, Rodney J; Frazier, Marsha L

2013-02-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle-related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle-related genes and 31 DNA repair-related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan-Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5 × 10(-4)). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16-6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome.

Cell cycle–related genes as modifiers of age of onset of colorectal cancer in Lynch syndrome: a large-scale study in non-Hispanic white patients

PubMed Central

Chen, Jinyun; Pande, Mala

2013-01-01

Heterogeneity in age of onset of colorectal cancer in individuals with mutations in DNA mismatch repair genes (Lynch syndrome) suggests the influence of other lifestyle and genetic modifiers. We hypothesized that genes regulating the cell cycle influence the observed heterogeneity as cell cycle–related genes respond to DNA damage by arresting the cell cycle to provide time for repair and induce transcription of genes that facilitate repair. We examined the association of 1456 single nucleotide polymorphisms (SNPs) in 128 cell cycle–related genes and 31 DNA repair–related genes in 485 non-Hispanic white participants with Lynch syndrome to determine whether there are SNPs associated with age of onset of colorectal cancer. Genotyping was performed on an Illumina GoldenGate platform, and data were analyzed using Kaplan–Meier survival analysis, Cox regression analysis and classification and regression tree (CART) methods. Ten SNPs were independently significant in a multivariable Cox proportional hazards regression model after correcting for multiple comparisons (P < 5×10–4). Furthermore, risk modeling using CART analysis defined combinations of genotypes for these SNPs with which subjects could be classified into low-risk, moderate-risk and high-risk groups that had median ages of colorectal cancer onset of 63, 50 and 42 years, respectively. The age-associated risk of colorectal cancer in the high-risk group was more than four times the risk in the low-risk group (hazard ratio = 4.67, 95% CI = 3.16–6.92). The additional genetic markers identified may help in refining risk groups for more tailored screening and follow-up of non-Hispanic white patients with Lynch syndrome. PMID:23125224

Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.

PubMed

Tanaka, Nobumichi; Asakawa, Isao; Fujimoto, Kiyohide; Anai, Satoshi; Hirayama, Akihide; Hasegawa, Masatoshi; Konishi, Noboru; Hirao, Yoshihiko

2012-09-14

To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer. We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone. Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce. Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

PubMed

Pérez-Beteta, Julián; Martínez-González, Alicia; Molina, David; Amo-Salas, Mariano; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Claramonte, Marta; Barcia, Juan A; Iglesias, Lidia; Avecillas, Josué; Albillo, David; Navarro, Miguel; Villanueva, José M; Paniagua, Juan C; Martino, Juan; Velásquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Delgado, María Del Carmen; Del Valle, Ana; Falkov, Anthony; Schucht, Philippe; Arana, Estanislao; Pérez-Romasanta, Luis; Pérez-García, Víctor M

2017-03-01

The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients.

Enteral nutrition volume is not correlated with lower respiratory tract infection in patients on mechanical ventilation.

PubMed

Colomar, A; Guardiola, B; Llompart-Pou, J A; Ayestarán, I; Rodríguez-Pilar, J; Ferreruela, M; Raurich, J M

To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). A retrospective secondary analysis was carried out. The Intensive Care Unit of a University Hospital. Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. Lower respiratory tract infection episodes. Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis.

PubMed

Bonsu, Kwadwo Osei; Owusu, Isaac Kofi; Buabeng, Kwame Ohene; Reidpath, Daniel D; Kadirvelu, Amudha

2017-04-01

Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF. This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use. Among Africans with HF, statin treatment was associated with significant reduction in mortality. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Clinical performance validation of PITX2 DNA methylation as prognostic biomarker in patients with head and neck squamous cell carcinoma.

PubMed

Sailer, Verena; Gevensleben, Heidrun; Dietrich, Joern; Goltz, Diane; Kristiansen, Glen; Bootz, Friedrich; Dietrich, Dimo

2017-01-01

Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc.). A total of 528 HNSCC patients from The Cancer Genome Atlas (TCGA) were included in the study. Death was defined as primary endpoint. PITX2 methylation was correlated with overall survival and clinicopathological parameters. PITX2 methylation was significantly associated with sex, tumor site, p16 status, and grade. In univariate Cox proportional hazards analysis, PITX2 hypermethylation analyzed as continuous and dichotomized variable was significantly associated with prolonged overall survival of HNSCC patients (continuous: hazard ratio (HR) = 0.19 [95%CI: 0.04-0.88], p = 0.034; dichotomized: HR = 0.52 [95%CI: 0.33-0.84], p = 0.007). In multivariate Cox analysis including established clinicopathological parameters, PITX2 promoter methylation was confirmed as prognostic factor (HR = 0.28 [95%CI: 0.09-0.84], p = 0.023). Using an independent analytical platform, PITX2 methylation was validated as a prognostic biomarker in HNSCC patients, identifying patients that potentially benefit from intensified surveillance and/or administration of adjuvant/neodjuvant treatment, i.e. immunotherapy.

PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)

PubMed Central

Liu, Minetta C; Pitcher, Brandelyn N; Mardis, Elaine R; Davies, Sherri R; Friedman, Paula N; Snider, Jacqueline E; Vickery, Tammi L; Reed, Jerry P; DeSchryver, Katherine; Singh, Baljit; Gradishar, William J; Perez, Edith A; Martino, Silvana; Citron, Marc L; Norton, Larry; Winer, Eric P; Hudis, Clifford A; Carey, Lisa A; Bernard, Philip S; Nielsen, Torsten O; Perou, Charles M; Ellis, Matthew J; Barry, William T

2016-01-01

PAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005 subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call, proliferation score, and risk of recurrence score (ROR-PT) for the evaluable subset of 1,311 treated patients. The interaction between DD-therapy benefit and intrinsic subtype was tested in a Cox proportional hazards model using two-sided alpha=0.05. Additional multivariable Cox models evaluated the proliferation and ROR-PT scores as continuous measures with selected clinical covariates. Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete data set (RFS; hazard ratio=1.20; 95% confidence interval=0.99–1.44) with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS (P<0.0001) irrespective of treatment assignment. No subtype-specific treatment effect on RFS was identified (interaction P=0.44). Proliferation and ROR-PT scores were prognostic for RFS (both P<0.0001), but no association with treatment benefit was seen (P=0.14 and 0.59, respectively). Results were similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures were highly prognostic but did not predict for improved outcomes with DD anthracycline- and taxane-based therapy. Clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize treatment based on expected risks of distant recurrence. PMID:28691057

Influence of diabetes on the risk of urothelial cancer according to body mass index: a 10-year nationwide population-based observational study.

PubMed

Bae, Woong Jin; Choi, Jin Bong; Moon, Hyong Woo; Park, Young Hyun; Cho, Hyuk Jin; Hong, Sung-Hoo; Lee, Ji Youl; Kim, Sae Woong; Han, Kyung-Do; Ha, U-Syn

2018-01-01

To examine the association between obesity and urothelial cancer, we used a representative data from the National Health Insurance System (NHIS). Participants included 826,170 men aged 20 years and older who experienced a health examination at least one time between 2004 and 2008. The study thus excluded people aged <20 years and women. We used a multivariate adjusted Cox regression analysis to examine the association between urothelial cancer and body mass index (BMI) via a hazard ratio (HR) and 95% confidence interval (CI). The age- or multivariable-adjusted HR for urothelial cancer was stratified by BMI. Men with a higher BMI were more likely to acquire urothelial cancer independent of variables. In the population with diabetes, there showed a considerable, increasing trend in the risk of urothelial cancer in the overweight and obesity group, compared to the group with the same BMI but without diabetes. This population-based study showed evidence of an association between obesity and the development of urothelial cancer, where the presence of diabetes increased the risk of urothelial cancer. Additionally, the higher the BMI, the higher the risk for urothelial cancer.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sole, Claudio V., E-mail: csole@iram.cl; School of Medicine, Complutense University, Madrid; Calvo, Felipe A.

Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-freemore » survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.« less

Impact of loneliness and depression on mortality: results from the Longitudinal Ageing Study Amsterdam.

PubMed

Holwerda, Tjalling J; van Tilburg, Theo G; Deeg, Dorly J H; Schutter, Natasja; Van, Rien; Dekker, Jack; Stek, Max L; Beekman, Aartjan T F; Schoevers, Robert A

2016-08-01

Loneliness is highly prevalent among older people, has serious health consequences and is an important predictor of mortality. Loneliness and depression may unfavourably interact with each other over time but data on this topic are scarce. To determine whether loneliness is associated with excess mortality after 19 years of follow-up and whether the joint effect with depression confers further excess mortality. Different aspects of loneliness were measured with the De Jong Gierveld scale and depression with the Centre for Epidemiologic Studies Depression Scale in a cohort of 2878 people aged 55-85 with 19 years of follow-up. Excess mortality hypotheses were tested with Kaplan-Meier and Cox proportional hazard analyses controlling for potential confounders. At follow-up loneliness and depression were associated with excess mortality in older men and women in bivariate analysis but not in multivariate analysis. In multivariate analysis, severe depression was associated with excess mortality in men who were lonely but not in women. Loneliness and depression are important predictors of early death in older adults. Severe depression has a strong association with excess mortality in older men who were lonely, indicating a lethal combination in this group. © The Royal College of Psychiatrists 2016.

National disparities in treatment package time for resected locally advanced head and neck cancer and impact on overall survival.

PubMed

Guttmann, David M; Kobie, Julie; Grover, Surbhi; Lin, Alexander; Lukens, John N; Mitra, Nandita; Rhodes, Karin V; Feng, Weiwei; Swisher-McClure, Samuel

2018-06-01

The purpose of this study was to determine national disparities in head and neck cancer treatment package time (the time interval from surgery through the completion of radiation) and the associated impact on survival. We conducted an observational cohort study using the National Cancer Database of 15 234 patients with resected head and neck cancer who underwent adjuvant radiotherapy from 2004-2012. Predictors of prolonged package time were identified by multivariable linear regression. Survival outcomes were assessed using a multivariable Cox model. Mean package time was 100 days (SD 23). Package time was 7.52 days (95% confidence interval [CI] 6.23-8.81; P < .001) longer with Medicaid versus commercial insurance. Low income and African American race also predicted for longer package times. All-cause mortality increased an average of 4% with each 1 week increase in treatment package time (hazard ratio [HR] 1.04; 95% CI 1.03-1.05; P < .001). Significant national socioeconomic disparities exist in treatment package time. Treatment delays in this setting may contribute to worse survival outcomes. © 2018 Wiley Periodicals, Inc.

Comparison and validation of statistical methods for predicting power outage durations in the event of hurricanes.

PubMed

Nateghi, Roshanak; Guikema, Seth D; Quiring, Steven M

2011-12-01

This article compares statistical methods for modeling power outage durations during hurricanes and examines the predictive accuracy of these methods. Being able to make accurate predictions of power outage durations is valuable because the information can be used by utility companies to plan their restoration efforts more efficiently. This information can also help inform customers and public agencies of the expected outage times, enabling better collective response planning, and coordination of restoration efforts for other critical infrastructures that depend on electricity. In the long run, outage duration estimates for future storm scenarios may help utilities and public agencies better allocate risk management resources to balance the disruption from hurricanes with the cost of hardening power systems. We compare the out-of-sample predictive accuracy of five distinct statistical models for estimating power outage duration times caused by Hurricane Ivan in 2004. The methods compared include both regression models (accelerated failure time (AFT) and Cox proportional hazard models (Cox PH)) and data mining techniques (regression trees, Bayesian additive regression trees (BART), and multivariate additive regression splines). We then validate our models against two other hurricanes. Our results indicate that BART yields the best prediction accuracy and that it is possible to predict outage durations with reasonable accuracy. © 2011 Society for Risk Analysis.

Bone sialoprotein is predictive of bone metastases in resectable non-small-cell lung cancer: a retrospective case-control study.

PubMed

Papotti, Mauro; Kalebic, Thea; Volante, Marco; Chiusa, Luigi; Bacillo, Elisa; Cappia, Susanna; Lausi, Paolo; Novello, Silvia; Borasio, Piero; Scagliotti, Giorgio V

2006-10-20

Bone metastases (BM) in non-small-cell lung cancer (NSCLC) may be detected at diagnosis or during the course of the disease, and are associated with a worse prognosis. Currently, there are no predictive or diagnostic markers to identify high-risk patients for metastatic bone dissemination. Thirty patients with resected NSCLC who subsequently developed BM were matched for clinicopathologic parameters to 30 control patients with resected NSCLC without any metastases and 26 patients with resected NSCLC and non-BM lesions. Primary tumors were investigated by immunohistochemistry for 10 markers involved in bone resorption or development of metastases. Differences among groups were estimated by chi2 test, whereas the prognostic impact of clinicopathologic parameters and marker expression was evaluated by univariate (Wilcoxon and Mantel-Cox tests) and multivariate (Cox proportional hazards regression model) analyses. The presence of bone sialoprotein (BSP) was strongly associated with bone dissemination (P < .001) and, independently, with worse outcome (P = .02, Mantel-Cox test), as defined by overall survival. To evaluate BSP protein expression in nonselected NSCLC, a series of 120 consecutive resected lung carcinomas was added to the study, and BSP prevalence reached 40%. No other markers showed a statistically significant difference among the three groups or demonstrated a prognostic impact, in terms of both overall survival and time interval to metastases. BSP protein expression in the primary resected NSCLC is strongly associated with BM progression and could be useful in identifying high-risk patients who could benefit from novel modalities of surveillance and preventive treatment.

Dual oxidase 1: A predictive tool for the prognosis of hepatocellular carcinoma patients.

PubMed

Chen, Shengsen; Ling, Qingxia; Yu, Kangkang; Huang, Chong; Li, Ning; Zheng, Jianming; Bao, Suxia; Cheng, Qi; Zhu, Mengqi; Chen, Mingquan

2016-06-01

Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real‑time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non‑cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

PubMed

Elshafei, Ahmed; Kovac, Evan; Dhar, Nivedita; Levy, David; Polascik, Thomas; Mouraviev, Vladimir; Yu, Changhong; Jones, J Stephen

2015-09-01

To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options. © 2015 Wiley Periodicals, Inc.

Kidney transplantation from deceased donors with elevated serum creatinine.

PubMed

Gallinat, Anja; Leerhoff, Sabine; Paul, Andreas; Molmenti, Ernesto P; Schulze, Maren; Witzke, Oliver; Sotiropoulos, Georgios C

2016-12-01

Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. All kidney transplants from 01-2000 to 12-2012 with donor creatinine ≥ 2 mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53 years and 5.1 years, respectively. After a median follow-up of 6.2 years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89 % and 96, 93, and 89 %, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine ≥2 mg/dl can be achieved when donor creatinine is <3.5 mg/dl, and the recipient has low comorbidities, is under 56 years of age, and remains in dialysis prior to KT for <6.8 years.

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke

PubMed Central

Wang, Huan; Lei, Leix; Zhang, Han-Qing; Gu, Zheng-Tian; Xing, Fang-Lan; Yan, Fu-Ling

2018-01-01

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS. PMID:29896437

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke.

PubMed

Deng, Qi-Wen; Li, Shuo; Wang, Huan; Lei, Leix; Zhang, Han-Qing; Gu, Zheng-Tian; Xing, Fang-Lan; Yan, Fu-Ling

2018-06-01

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS.

Periodontal disease, tooth loss and colorectal cancer risk: Results from the Nurses' Health Study.

PubMed

Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A; Ogino, Shuji; Chan, Andrew T; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S; Stampfer, Meir J; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

2017-02-01

Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses' Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25-32 teeth, the multivariable HR (95% CI) for CRC for women with <17 teeth was 1.20 (1.04-1.39). With regard to tumor site, the HRs (95% CIs) for the same comparison were 1.23 (1.01-1.51) for proximal colon cancer, 1.03 (0.76-1.38) for distal colon cancer and 1.48 (1.07-2.05) for rectal cancer. In addition, compared to those without periodontal disease, HRs for CRC were 0.91 (95% CI 0.74-1.12) for periodontal disease, and 1.22 (95% CI 0.91-1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. © 2016 UICC.

Predictors of premature gonadal failure in patients with systemic lupus erythematosus. Results from LUMINA, a multiethnic US cohort (LUMINA LVIII).

PubMed

González, L A; McGwin, G; Durán, S; Pons-Estel, G J; Apte, M; Vilá, L M; Reveille, J D; Alarcón, G S

2008-08-01

To examine the predictors of time to premature gonadal failure (PGF) in patients with systemic lupus erythematosus from LUMINA, a multiethnic US cohort. PGF was defined according to the SLICC Damage Index (SDI). Factors associated with time to PGF occurrence were examined by univariable and multivariable Cox proportional hazards regression analyses: three models according to cyclophosphamide use, at T0 (model 1), over time (model 2) and the total number of intravenous pulses (model 3). Thirty-seven of 316 women (11.7%) developed PGF (19 Texan-Hispanics, 14 African-Americans, four Caucasians and no Puerto Rican-Hispanics). By multivariable analyses, older age at T0 (hazards ratio (HR) = 1.10-1.14; 95% CI 1.02-1.05 to 1.19-1.23) and disease activity (Systemic Lupus Activity Measure-Revised) in all models (HR = 1.22-1.24; 95% CI 1.10-1.12 to 1.35-1.37), Texan-Hispanic ethnicity in models 2 and 3 (HR = 4.06-5.07; 95% CI 1.03-1.25 to 15.94-20.47) and cyclophosphamide use in models 1 and 3 (1-6 pulses) (HR = 4.01-4.65; 95% CI 1.55-1.68 to 9.56-13.94) were predictors of a shorter time to PGF. Disease activity and Texan-Hispanic ethnicity emerged as predictors of a shorter time to PGF while the associations with cyclophosphamide use and older age were confirmed. Furthermore, cyclophosphamide induction therapy emerged as an important determinant of PGF.

Muscular Strength and Incident Hypertension in Normotensive and Prehypertensive Men

PubMed Central

Maslow, Andréa L.; Sui, Xuemei; Colabianchi, Natalie; Hussey, Jim; Blair, Steven N.

2009-01-01

The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. Purpose This study evaluated the strength-HTN association with and without accounting for CRF. Methods Participants were 4147 men (20–82 years) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a 1-repetition maximal leg and a 1-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals of incident HTN events according to exposure categories. Results During a mean follow-up of 19 years, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HRs of hypertension in normotensive men comparing middle and high strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HRs of hypertension in baseline prehypertensive men comparing middle and high strength thirds to the lowest third were significant at 0.73 and 0.72 (p=.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (p=.26). Conclusions The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF. PMID:19927030

Night shift work and incident diabetes among U.S. black women

PubMed Central

Vimalananda, Varsha G.; Palmer, Julie R.; Gerlovin, Hanna; Wise, Lauren A.; Rosenzweig, James L.; Rosenberg, Lynn; Narváez, Edward A. Ruiz

2015-01-01

Aims To assess shift work in relation to incident type 2 diabetes among African American women. Methods In the Black Women's Health Study (BWHS), an ongoing prospective cohort study, we followed 28,041 participants for incident diabetes during 2005-2013. They answered questions in 2005 about having worked the night shift. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for incident diabetes using Cox proportional hazards models. The basic multivariable model included age, time period, family history of diabetes, education, and neighborhood SES. In further models, we controlled for lifestyle factors and body mass index (BMI). Results Over the 8 years of follow-up, there were 1,786 incident diabetes cases. Relative to never having worked the night shift, HRs (95% CI) of diabetes were 1.17 (1.04, 1.31) for 1-2 years of night shift work, 1.23 (1.06, 1.41) for 3-9 years, and 1.42 (1.19, 1.70) for ≥ 10 years (P-trend < 0.0001). The monotonic positive association between night shift work and type 2 diabetes remained after multivariable adjustment (P-trend = 0.02). The association did not vary by obesity status, but was stronger in women aged < 50 years. Conclusions Long durations of shift work were associated with an increased risk of type 2 diabetes. The association was only partially explained by lifestyle factors and BMI. A better understanding of the mechanisms by which shift work may affect risk of diabetes is needed in view of the high prevalence of shift work among U.S. workers. PMID:25586362

Prognostic significance of hyperfibrinogenemia in patients with esophageal squamous cell carcinoma.

PubMed

Suzuki, Takashi; Shimada, Hideaki; Nanami, Tatsuki; Oshima, Yoko; Yajima, Satoshi; Washizawa, Naohiro; Kaneko, Hironori

2017-06-01

Preoperative hyperfibrinogenemia is associated with inflammatory mediators and a poor prognosis in several types of cancer. However, there is no published information on the monitoring of patients with preoperative hyperfibrinogenemia after surgery. The aim of the study reported here was to assess the clinicopathological and prognostic significance of plasma fibrinogen levels in patients with esophageal squamous cell carcinoma before and after surgical treatment. Plasma fibrinogen levels were analyzed before surgical treatment (endoscopic submucosal dissection and surgery) in 82 patients with esophageal squamous cell carcinoma. The clinicopathological significance of plasma fibrinogen levels and the relationship of plasma fibrinogen levels with several biomarkers were evaluated. The cutoff value for hyperfibrinogenemia was 321 mg/dl. Univariate and multivariate analysis using the Cox proportional hazards model were performed to evaluate the prognostic significance of plasma fibrinogen levels. The changing patterns of plasma fibrinogen were monitored after surgical treatment to evaluate prognostic impact. Hyperfibrinogenemia was significantly associated with advanced pathological stage of cancer and high C-reactive protein levels. Plasma fibrinogen levels significantly decreased after surgical treatment in recurrence-free patients but did not decrease in patients with recurrence. The multivariate analysis indicated that preoperative hyperfibrinogenemia was an independent prognostic factor for poor survival (hazard ratio 1.005, 95% confidence interval 1.000-1.010; P = 0.039). Preoperative hyperfibrinogenemia was associated with inflammatory mediators, tumor progression, and poor survival in patients with esophageal squamous cell carcinoma. The absence of a decrease in plasma fibrinogen levels after surgical treatment may indicate the possibility of tumor recurrence.

SOX9 expression predicts relapse of stage II colon cancer patients.

PubMed

Marcker Espersen, Maiken Lise; Linnemann, Dorte; Christensen, Ib Jarle; Alamili, Mahdi; Troelsen, Jesper T; Høgdall, Estrid

2016-06-01

The aim of this study was to investigate if the protein expression of sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients. One hundred forty-four patients with stage II primary colon cancer were retrospectively enrolled in the study. SOX9 expression was evaluated by immunohistochemistry, and mismatch repair status was assessed by both immunohistochemistry and promoter hypermethylation assay. High SOX9 expression at the invasive front was significantly associated with lower risk of relapse when including the SOX9 expression as a continuous variable (from low to high expression) in univariate (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .01) and multivariate Cox proportional hazards analyses (HR, 0.75; 95% CI, 0.58-0.96; P = .02), adjusting for mismatch repair deficiency and histopathologic risk factors. Conversely, low SOX9 expression at the invasive front was significantly associated with high risk of relapse, when including SOX9 expression as a dichotomous variable, in univariate (HR, 2.32; 95% CI, 1.14-4.69; P = .02) and multivariate analyses (HR, 2.32; 95% CI, 1.14-4.69; P = .02), adjusting for histopathologic risk factors and mismatch repair deficiency. In conclusion, high levels of SOX9 of primary stage II colon tumors predict low risk of relapse, whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

PubMed

Perez, Marco V; Hoffmann, Thomas J; Tang, Hua; Thornton, Timothy; Stefanick, Marcia L; Larson, Joseph C; Kooperberg, Charles; Reiner, Alex P; Caan, Bette; Iribarren, Carlos; Risch, Neil

2013-09-01

Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans. © 2013.

Serum and dietary magnesium and incidence of atrial fibrillation in whites and in African Americans--Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Misialek, Jeffrey R; Lopez, Faye L; Lutsey, Pamela L; Huxley, Rachel R; Peacock, James M; Chen, Lin Y; Soliman, Elsayed Z; Agarwal, Sunil K; Alonso, Alvaro

2013-01-01

Low serum magnesium (Mg) has been associated with an increased risk of cardiovascular disease (CVD), including ventricular arrhythmias, but the association between serum or dietary Mg and atrial fibrillation (AF) has not been investigated. A total of 14,290 men and women (75% white; 53% female; mean age, 54 years) free of AF at baseline participating in the Atherosclerosis Risk in Communities study in the United States, were studied. Incident AF cases through 2009 were ascertained from electrocardiograms, hospital discharge codes, and death certificates. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with serum and dietary Mg quintiles. Over a median follow-up time of 20.6 years, 1,755 incident AF cases were identified. In multivariate models, lower serum Mg was associated with higher AF risk: compared to individuals in the middle quintile (≥ 0.80-0.83 mmol/L), the HR (95% CI) of AF in quintiles 1, 2, 4, and 5 were 1.34 (1.16-1.54), 0.99 (0.85-1.16), 1.04 (0.90-1.22), and 1.06 (0.91-1.23), respectively. There was no evidence of significant interactions between serum Mg and sex or race. No association between dietary Mg and AF risk was observed. Lower serum Mg was associated with a higher AF risk, and this association was not different between whites and African Americans. Dietary Mg was not associated with AF risk.

Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies.

PubMed

Shimazu, T; Wakai, K; Tamakoshi, A; Tsuji, I; Tanaka, K; Matsuo, K; Nagata, C; Mizoue, T; Inoue, M; Tsugane, S; Sasazuki, S

2014-06-01

Prospective evidence is inconsistent regarding the association between vegetable/fruit intake and the risk of gastric cancer. In an analysis of original data from four population-based prospective cohort studies encompassing 191 232 participants, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of gastric cancer incidence according to vegetable and fruit intake and conducted a meta-analysis of HRs derived from each study. During 2 094 428 person-years of follow-up, 2995 gastric cancer cases were identified. After adjustment for potential confounders, we found a marginally significant decrease in gastric cancer risk in relation to total vegetable intake but not total fruit intake: the multivariate-adjusted HR (95% CI; P for trend) for the highest versus the lowest quintile of total vegetable intake was 0.89 (0.77-1.03; P for trend = 0.13) among men and 0.83 (0.67-1.03; P for trend = 0.40) among women. For distal gastric cancer, the multivariate HR for the highest quintile of total vegetable intake was 0.78 (0.63-0.97; P for trend = 0.02) among men. This pooled analysis of data from large prospective studies in Japan suggests that vegetable intake reduces gastric cancer risk, especially the risk of distal gastric cancer among men. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Carotid intima-media thickness is a novel predictor of new onset of hypertension in normotensive subjects.

PubMed

Takase, Hiroyuki; Sugiura, Tonomori; Murai, Shunsuke; Yamashita, Sumiyo; Ohte, Nobuyuki; Dohi, Yasuaki

2017-08-01

Increased carotid intima-media thickness (IMT) in individuals without hypertension might indicate other factors promoting the atherosclerotic process that are often simultaneously clustered in individuals. The present study tested the hypothesis that carotid IMT predicts new onset of hypertension in the normotensive subjects.A total of 867 participants were enrolled from our yearly physical checkup program and their carotid IMT was measured. After a baseline examination, the subjects were followed up for a median of 1091 days with the endpoint being the development of hypertension.At baseline, the carotid IMT value was 0.75 ± 0.16 mm. Hypertension developed in 184 subjects during the follow-up (76.9/1000 person-years). The incidence of hypertension was increased across the tertiles of the carotid IMT value (39.6, 70.0, and 134.5/1000 person-years in the first, second, and third tertiles, respectively, P < .001 by log-rank test). Multivariate Cox-hazard analysis after adjustment identified carotid IMT, taken as a continuous variable, as a significant predictor of new-onset hypertension (hazard ratio = 7.08, 95% confidence interval = 3.06-15.39). Furthermore, multivariate linear regression analyses indicated a significant correlation between the carotid IMT at baseline and yearly increases in systolic blood pressure during the follow-up period (β = 0.189, P < .001).Carotid IMT is an independent predictor of hypertension onset in normotensive subjects. The findings also suggested a close association between increased carotid IMT and blood pressure.

Carotid intima-media thickness is a novel predictor of new onset of hypertension in normotensive subjects

PubMed Central

Takase, Hiroyuki; Sugiura, Tonomori; Murai, Shunsuke; Yamashita, Sumiyo; Ohte, Nobuyuki; Dohi, Yasuaki

2017-01-01

Abstract Increased carotid intima-media thickness (IMT) in individuals without hypertension might indicate other factors promoting the atherosclerotic process that are often simultaneously clustered in individuals. The present study tested the hypothesis that carotid IMT predicts new onset of hypertension in the normotensive subjects. A total of 867 participants were enrolled from our yearly physical checkup program and their carotid IMT was measured. After a baseline examination, the subjects were followed up for a median of 1091 days with the endpoint being the development of hypertension. At baseline, the carotid IMT value was 0.75 ± 0.16 mm. Hypertension developed in 184 subjects during the follow-up (76.9/1000 person-years). The incidence of hypertension was increased across the tertiles of the carotid IMT value (39.6, 70.0, and 134.5/1000 person-years in the first, second, and third tertiles, respectively, P < .001 by log-rank test). Multivariate Cox-hazard analysis after adjustment identified carotid IMT, taken as a continuous variable, as a significant predictor of new-onset hypertension (hazard ratio = 7.08, 95% confidence interval = 3.06–15.39). Furthermore, multivariate linear regression analyses indicated a significant correlation between the carotid IMT at baseline and yearly increases in systolic blood pressure during the follow-up period (β = 0.189, P < .001). Carotid IMT is an independent predictor of hypertension onset in normotensive subjects. The findings also suggested a close association between increased carotid IMT and blood pressure. PMID:28767608

Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

PubMed

Liss, Michael A; White, Martha; Natarajan, Loki; Parsons, J Kellogg

2017-06-01

The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as "did no exercise" vs. "light, moderate, or vigorous exercise in ≥ 10-minute bouts"), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than "no exercise". Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. Published by Elsevier Inc.

Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis.

PubMed

Jésus, P; Fayemendy, P; Nicol, M; Lautrette, G; Sourisseau, H; Preux, P-M; Desport, J-C; Marin, B; Couratier, P

2018-01-01

The aim of this study was to investigate patients with amyotrophic lateral sclerosis in order to determine their nutritional, neurological and respiratory parameters, and survival according to metabolic level. Nutritional assessment included resting energy expenditure (REE) measured by indirect calorimetry [hypermetabolism if REE variation (ΔREE) > 10%] and fat mass (FM) using impedancemetry. Neurological assessment included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score. Survival analysis used the Kaplan-Meier method and multivariate Cox model. A total of 315 patients were analysed. Median age at diagnosis was 65.9 years and 55.2% of patients were hypermetabolic. With regard to the metabolic level (ΔREE: < 10%, 10-20% and >20%), patients with ΔREE > 20% initially had a lower FM(29.7% vs. 32.1% in those with ΔREE ≤10%; P = 0.0054). During follow-up, the median slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised tended to worsen more in patients with ΔREE > 20% (-1.4 vs. -1.0 points/month in those with ΔREE ≤10%; P = 0.07). Overall median survival since diagnosis was 18.4 months. ΔREE > 20% tended to increase the risk of dying compared with ΔREE ≤10% (hazard ratio, 1.33; P = 0.055). In multivariate analysis, an increased REE:FM ratio was independently associated with death (hazard ratio, 1.005; P = 0.001). Hypermetabolism is present in more than half of patients with amyotrophic lateral sclerosis. It modifies the body composition at diagnosis, and patients with hypermetabolism >20% have a worse prognosis than those without hypermetabolism. © 2017 EAN.

Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in the Japanese Normotensive General Population

PubMed Central

Takase, Hiroyuki; Sugiura, Tomonori; Kimura, Genjiro; Ohte, Nobuyuki; Dohi, Yasuaki

2015-01-01

Background Although there is a close relationship between dietary sodium and hypertension, the concept that persons with relatively high dietary sodium are at increased risk of developing hypertension compared with those with relatively low dietary sodium has not been studied intensively in a cohort. Methods and Results We conducted an observational study to investigate whether dietary sodium intake predicts future blood pressure and the onset of hypertension in the general population. Individual sodium intake was estimated by calculating 24-hour urinary sodium excretion from spot urine in 4523 normotensive participants who visited our hospital for a health checkup. After a baseline examination, they were followed for a median of 1143 days, with the end point being development of hypertension. During the follow-up period, hypertension developed in 1027 participants (22.7%). The risk of developing hypertension was higher in those with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to 1.50). In multivariate Cox proportional hazards regression analysis, baseline sodium intake and the yearly change in sodium intake during the follow-up period (as continuous variables) correlated with the incidence of hypertension. Furthermore, both the yearly increase in sodium intake and baseline sodium intake showed significant correlations with the yearly increase in systolic blood pressure in multivariate regression analysis after adjustment for possible risk factors. Conclusions Both relatively high levels of dietary sodium intake and gradual increases in dietary sodium are associated with future increases in blood pressure and the incidence of hypertension in the Japanese general population. PMID:26224048

Predictors and Patterns of Local, Regional, and Distant Failure in Squamous Cell Carcinoma of the Vulva.

PubMed

Bogani, Giorgio; Cromi, Antonella; Serati, Maurizio; Uccella, Stefano; Donato, Violante Di; Casarin, Jvan; Naro, Edoardo Di; Ghezzi, Fabio

2017-06-01

To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

Kinetic Risk Factors of Running-Related Injuries in Female Recreational Runners.

PubMed

Napier, Christopher; MacLean, Christopher L; Maurer, Jessica; Taunton, Jack E; Hunt, Michael A

2018-05-30

Our objective was to prospectively investigate the association of kinetic variables with running-related injury (RRI) risk. Seventy-four healthy female recreational runners ran on an instrumented treadmill while 3D kinetic and kinematic data were collected. Kinetic outcomes were vertical impact transient, average vertical loading rate, instantaneous vertical loading rate, active peak, vertical impulse, and peak braking force (PBF). Participants followed a 15-week half-marathon training program. Exposure time (hours of running) was calculated from start of program until onset of injury, loss to follow-up, or end of program. After converting kinetic variables from continuous to ordinal variables based on tertiles, Cox proportional hazard models with competing risks were fit for each variable independently, before analysis in a forward stepwise multivariable model. Sixty-five participants were included in the final analysis, with a 33.8% injury rate. PBF was the only kinetic variable that was a significant predictor of RRI. Runners in the highest tertile (PBF <-0.27 BW) were injured at 5.08 times the rate of those in the middle tertile and 7.98 times the rate of those in the lowest tertile. When analyzed in the multivariable model, no kinetic variables made a significant contribution to predicting injury beyond what had already been accounted for by PBF alone. Findings from this study suggest PBF is associated with a significantly higher injury hazard ratio in female recreational runners and should be considered as a target for gait retraining interventions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study.

PubMed

Khan, Nabeel; Patel, Dhruvan; Trivedi, Chinmay; Shah, Yash; Lichtenstein, Gary; Lewis, James; Yang, Yu-Xiao

2018-01-05

Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5-ASA alone vs matched patients without IBD. In study 2, we compared the incidence of herpes zoster among patients with IBD treated with only 5-ASA, with thiopurines, with antagonists of tumor necrosis factor (TNF), with a combination of thiopurines and TNF antagonists, and with vedolizumab. We used multivariable Cox regression to estimate the hazard ratios and 95% CIs for herpes zoster associated with IBD in study 1 and with different treatments in study 2. We also estimated the incidence rate of herpes zoster based on age and IBD medication subgroups. Compared to no IBD, ulcerative colitis (UC) and Crohn's disease (CD) were each associated with significantly increased risk of herpes zoster infection. In multivariable Cox regression (compared to no IBD), UC, CD, or IBD treated with 5-ASA treatment alone was associated with significantly increased risk of herpes zoster, with adjusted HRs (AHR) of 1.81 for UC (95% CI, 1.56-2.11), 1.56 for CD (95% CI, 1.28-1.91), and 1.72 for treated IBD (95% CI, 1.51-1.96). In multivariable Cox regression analysis, compared to exposure to 5-ASA alone, exposure to thiopurines (AHR, 1.47; 95% CI, 1.31-1.65) or a combination of thiopurines and TNF antagonists (AHR, 1.65; 95% CI, 1.22-2.23) was associated with increased risk of herpes zoster. However, exposure to TNF antagonists alone (AHR, 1.15; 95% CI, 0.96-1.38) was not associated with increased risk of herpes zoster. The incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD (older than 60 years). In 2 retrospective studies of Veteran populations, we associated IBD and treatment with thiopurines, alone or in combination with TNF antagonists, with increased risk of herpes zoster. With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Predictors of the patency of self-expandable metallic stents in malignant gastroduodenal obstruction.

PubMed

Kim, Seung Han; Chun, Hoon Jai; Yoo, In Kyung; Lee, Jae Min; Nam, Seung Joo; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

2015-08-14

To investigate the predictive factors of self-expandable metallic stent patency after stent placement in patients with inoperable malignant gastroduodenal obstruction. A total of 116 patients underwent stent placements for inoperable malignant gastroduodenal obstruction at a tertiary academic center. Clinical success was defined as acceptable decompression of the obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated patient comorbidities and clinical statuses using the World Health Organization's scoring system and categorized patient responses to chemotherapy using the Response Evaluation Criteria in Solid Tumors criteria. We analyzed the relationships between possible predictive factors and stent patency. Self-expandable metallic stent placement was technically successful in all patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92, 95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CEA levels can easily be measured at the time of stent placement and may help clinicians to predict stent patency and determine the appropriate stent procedure.

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

PubMed

Frederick, Wayne A I; Ames, Sarah; Downing, Stephanie R; Oyetunji, Tolulope A; Chang, David C; Leffall, Lasalle D

2010-06-01

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Does maintenance CBT contribute to long-term treatment response of panic disorder with or without agoraphobia? A randomized controlled clinical trial.

PubMed

White, Kamila S; Payne, Laura A; Gorman, Jack M; Shear, M Katherine; Woods, Scott W; Saksa, John R; Barlow, David H

2013-02-01

We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either 9 monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. M-CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up. Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-month follow-up (hazards ratio = 1.15, p < .01). M-CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome for panic disorder with and without agoraphobia.

Effectiveness of pneumococcal vaccination in older adults with chronic respiratory diseases: results of the EVAN-65 study.

PubMed

Ochoa-Gondar, Olga; Vila-Corcoles, Angel; Ansa, Xavier; Rodriguez-Blanco, T; Salsench, Elisabeth; de Diego, Cinta; Raga, Xavier; Gomez, Frederic; Valdivieso, Empar; Fuentes, Cruzma; Palacios, Laura

2008-04-07

A prospective cohort study evaluating the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine was conducted among 1298 Spanish older adults with chronic respiratory diseases (bronchitis, emphysema or asthma) who were followed between 2002 and 2005. Main outcomes were all-cause community-acquired pneumonia (CAP) and 30 days mortality from CAP. The association between vaccination and the risk of each outcome was evaluated by multivariable Cox proportional-hazard models adjusted for age and comorbidity pneumococcal vaccination did not alter significantly the risk of overall CAP (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.56-1.07) and 30 days mortality from CAP (HR: 0.87; 95% CI: 0.33-2.28). However, a borderline significant reduction of 30% in the risk of all-cause hospitalisation for CAP was observed among vaccinated subjects (HR: 0.70; 95% CI: 0.48-1.00; p=0.052). The effectiveness of the vaccine on the combined endpoint of pneumococcal and unknown organism infections reached 34% (HR: 0.66; 95% CI: 0.43-1.01; p=0.059). Although our findings suggest moderate benefits from the vaccination, the evidence of clinical effectiveness appears limited.

Red meat consumption and risk of heart failure in male physicians

PubMed Central

Ashaye, A; Gaziano, J; Djoussé, L

2010-01-01

Background and Aims Heart failure (HF) remains a major public health issue. Red meat and dietary heme iron have been associated with an increased risk of coronary heart disease and hypertension, two major risk factors for HF. However, it is not known whether red meat intake influences the risk of HF. We therefore examined the association between red meat consumption and incident HF. Methods and Results We prospectively studied 21,120 apparently healthy men (mean age 54.6 y) from the Physicians’ Health Study (1982–2008). Red meat was assessed by an abbreviated food questionnaire and incident HF was ascertained through annual follow-up questionnaires. We used Cox proportional hazard models to estimate hazard ratios. In a multivariable model, there was a positive and graded relation between red meat consumption and HF [hazard ratio (95% CI) of 1.0 (reference), 1.02 (0.85–1.22), 1.08 (0.90–1.30), 1.17 (0.97–1.41), and 1.24 (1.03–1.48) from the lowest to the highest quintile of red meat, respectively (p for trend 0.007)]. This association was observed for HF with (p for trend 0. 035) and without (p for trend 0.038) antecedent myocardial infarction. Conclusion Our data suggest that higher intake of red meat is associated with an increased risk of HF. PMID:20675107

Red meat and processed meat intake and risk for cutaneous melanoma in white women and men: Two prospective cohort studies.

PubMed

Yen, Hsi; Li, Wen-Qing; Dhana, Ashar; Li, Tricia; Qureshi, Abrar; Cho, Eunyoung

2018-04-24

Red and processed meat consumption has been associated with increased risk for several cancers, but the association with cutaneous melanoma risk has been inconclusive. To investigate the association between red and processed meat intake and melanoma risk. Dietary information was assessed by using food frequency questionnaires in 2 prospective cohorts: 75,263 women from the Nurses' Health Study (1984-2010) and 48,523 men from the Health Professionals Follow-up Study (1986-2010). Melanoma cases were confirmed by reviewing pathology records. Pooled multivariable hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. A total of 679 female and 639 male melanoma cases were documented during follow-up. Red and processed meat intake was inversely associated with melanoma risk (P = .002 for trend); the pooled hazard ratios (95% confidence intervals) of the 2 cohorts were 1.00 (reference), 1.00 (0.87-1.14), 0.98 (0.86-1.13), 0.89 (0.77-1.02), and 0.81 (0.70-0.95) for increasing quintiles of intake. Findings might have limited generalizability, considering that the cohorts were limited to white health professionals. Red and processed meat intake was inversely associated with melanoma risk in these 2 cohorts. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Meat consumption and pancreatic cancer risk among men and women in the Cancer Prevention Study-II Nutrition Cohort.

PubMed

McCullough, Marjorie L; Jacobs, Eric J; Shah, Roma; Campbell, Peter T; Wang, Ying; Hartman, Terryl J; Gapstur, Susan M

2018-01-01

Prospective cohort studies suggest that red and processed meat consumption is associated with increased risk of pancreatic cancer among men, but not women. However, evidence is limited, and less evidence exists for other types of meat. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) for the association of meat consumption, by type, with pancreatic cancer risk among 138,266 men and women in the Cancer Prevention Study-II Nutrition Cohort. Diet was assessed at baseline in 1992, and 10 years earlier, at enrollment into the parent CPS-II mortality cohort. 1,156 pancreatic cancers were verified through 2013. Red meat, processed meat, and fish intake at baseline were not associated with pancreatic cancer risk. However, for long-term red and processed meat consumption (highest quartiles in 1982 and 1992, vs. lowest quartiles), risk appeared different in men [hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.90, 1.95] and women (HR 0.72, 95% CI 0.47, 1.10, p heterogeneity by sex = 0.05). Poultry consumption in 1992 was associated with increased pancreatic cancer risk (HR 1.27, 95% CI 1.04, 1.55, p trend = 0.01, top vs. bottom quintile). The associations of meat consumption with pancreatic cancer risk remain unclear and further research, particularly of long-term intake, is warranted.

Baseline Predictors of Missed Visits in the Look AHEAD Study

PubMed Central

Fitzpatrick, Stephanie L.; Jeffery, Robert; Johnson, Karen C.; Roche, Cathy C.; Van Dorsten, Brent; Gee, Molly; Johnson, Ruby Ann; Charleston, Jeanne; Dotson, Kathy; Walkup, Michael P.; Hill-Briggs, Felicia; Brancati, Frederick L.

2013-01-01

Objective To identify baseline attributes associated with consecutively missed data collection visits during the first 48 months of Look AHEAD—a randomized, controlled trial in 5145 overweight/obese adults with type 2 diabetes designed to determine the long-term health benefits of weight loss achieved by lifestyle change. Design and Methods The analyzed sample consisted of 5016 participants who were alive at month 48 and enrolled at Look AHEAD sites. Demographic, baseline behavior, psychosocial factors, and treatment randomization were included as predictors of missed consecutive visits in proportional hazard models. Results In multivariate Cox proportional hazard models, baseline attributes of participants who missed consecutive visits (n=222) included: younger age ( Hazard Ratio [HR] 1.18 per 5 years younger; 95% Confidence Interval 1.05, 1.30), higher depression score (HR 1.04; 1.01, 1.06), non-married status (HR 1.37; 1.04, 1.82), never self-weighing prior to enrollment (HR 2.01; 1.25, 3.23), and randomization to minimal vs. intensive lifestyle intervention (HR 1.46; 1.11, 1.91). Conclusions Younger age, symptoms of depression, non-married status, never self-weighing, and randomization to minimal intervention were associated with a higher likelihood of missing consecutive data collection visits, even in a high-retention trial like Look AHEAD. Whether modifications to screening or retention efforts targeted to these attributes might enhance long-term retention in behavioral trials requires further investigation. PMID:23996977

Frequent methamphetamine injection predicts emergency department utilization among street-involved youth

PubMed Central

Marshall, B.D.L.; Grafstein, E.; Buxton, J.A.; Qi, J.; Wood, E.; Shoveller, J.A.; Kerr, T.

2011-01-01

SUMMARY Objectives Methamphetamine (MA) use has been associated with health problems that commonly present in the emergency department (ED). This study sought to determine whether frequent MA injection was a risk factor for ED utilization among street-involved youth. Study design Prospective cohort study. Methods Data were derived from a street-involved youth cohort known as the ‘At Risk Youth Study’. Behavioural data including MA use were linked to ED records at a major inner-city hospital. Kaplan-Meier and Cox proportional hazards methods were used to determine the risk factors for ED utilization. Results Between September 2005 and January 2007, 427 eligible participants were enrolled, among whom the median age was 21 (interquartile range 19–23) years and 154 (36.1%) were female. Within 1 year, 163 (38.2%) visited the ED, resulting in an incidence density of 53.7 per 100 person-years. ED utilization was significantly higher among frequent (i.e. ≥daily) MA injectors (log-rank P=0.004). In multivariate analysis, frequent MA injection was associated with an increased hazard of ED utilization (adjusted hazard ratio=1.84, 95% confidence interval 1.04–3.25; P=0.036). Conclusions Street-involved youth who frequently inject MA appear to be at increased risk of ED utilization. The integration of MA-specific addiction treatment services within emergency care settings for high-risk youth is recommended. PMID:22133669

Association of Time between Surgery and Adjuvant Therapy with Survival in Oral Cavity Cancer.

PubMed

Chen, Michelle M; Harris, Jeremy P; Orosco, Ryan K; Sirjani, Davud; Hara, Wendy; Divi, Vasu

2018-06-01

Objective The National Cancer Center Network recommends starting radiation therapy within 6 weeks after surgery for oral cavity squamous cell carcinoma (OCSCC), but there is limited evidence of the importance of the total time from surgery to completion of radiation therapy (package time). We set out to determine if there was an association between package time and survival in OCSCC and to evaluate the impact of treatment location on outcomes. Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods We reviewed the records of patients with OCSCC who completed postoperative radiation therapy at an academic medical center from 2008 to 2016. The primary endpoints were overall survival and recurrence-free survival. Statistical analysis included χ 2 tests and Cox proportional hazards regressions. Results We identified 132 patients with an average package time of 12.6 weeks. On multivariate analysis, package time >11 weeks was independently associated with decreased overall survival (hazard ratio, 6.68; 95% CI, 1.42-31.44) and recurrence-free survival (hazard ratio, 2.94; 95% CI, 1.20-7.18). Patients who received radiation therapy at outside facilities were more likely to have treatment delays (90.2% vs 62.9%, P = .001). Conclusions Prolonged package times are associated with decreased overall and recurrence-free survival among patients with OCSCC. Patients who received radiation therapy at outside facilities are more likely to have prolonged package times.

APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease

PubMed Central

Ma, Lijun; Langefeld, Carl D.; Comeau, Mary E.; Bonomo, Jason A.; Rocco, Michael V.; Burkart, John M.; Divers, Jasmin; Palmer, Nicholette D.; Hicks, Pamela J.; Bowden, Donald W.; Lea, Janice P.; Krisher, Jenna O.; Clay, Margo J.; Freedman, Barry I.

2016-01-01

Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with non-diabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 non-diabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities. Outcomes were provided by the ESRD Network 6-Southeastern Kidney Council Standardized Information Management System. Dates of death, receipt of a kidney transplant, and loss to follow-up were recorded. Outcomes were censored at the date of transplantation or through July 1, 2015. Multivariable Cox proportional hazards models were computed separately in patients with non-diabetic and diabetic ESRD, adjusting for the covariates age, gender, comorbidities, ancestry, and presence of an arteriovenous fistula or graft at dialysis initiation. In non-diabetic ESRD, patients with two (vs. zero/one) APOL1 renal-risk variants had significantly longer dialysis survival (hazard ratio 0.57); a pattern not observed in patients with diabetes-associated ESRD (hazard ratio 1.29). Thus, two APOL1 renal-risk variants are associated with longer dialysis survival in African Americans without diabetes, potentially relating to presence of renal-limited disease or less atherosclerosis. PMID:27157696

Uremic Pruritus is Associated with Two-Year Cardiovascular Mortality in Long Term Hemodialysis Patients.

PubMed

Weng, Cheng-Hao; Hu, Ching-Chih; Yen, Tzung-Hai; Hsu, Ching-Wei; Huang, Wen-Hung

2018-06-15

Uremic pruritus (UP) is an unpleasant complication in patients undergoing maintenance dialysis. Cardiovascular and infection related deaths are the major causes of mortality in patients undergoing dialysis. Studies on the correlation between cardiovascular or infection related mortality and UP are limited. We analyze 866 maintenance hemodialysis (MHD) patients in our hemodialysis centers. Clinical parameters and 24-month cardiovascular and infection-related mortality are recorded. The associations between all-cause, cardiovascular and infection related mortality with clinical data including UP are analyzed. Multivariate Cox regression demonstrated that UP is a significantly predictor for 24-month cardiovascular mortality in the MHD patients (Hazard ratio: 3.164; 95% confidence interval, 1.743-5.744; p < 0.001). Uremic pruritus is one of the predictor of 24-month cardiovascular mortality in MHD patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Analysis of cohort studies with multivariate and partially observed disease classification data.

PubMed

Chatterjee, Nilanjan; Sinha, Samiran; Diver, W Ryan; Feigelson, Heather Spencer

2010-09-01

Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.

Analysis of surgical outcomes of diverticular disease of the colon.

PubMed

Miyaso, Hideaki; Iwakawa, Kazuhide; Kitada, Koji; Kimura, Yuji; Isoda, Kenta; Nishie, Manabu; Hamano, Ryosuke; Tokunaga, Naoyuki; Tsunemitsu, Yosuke; Ohtsuka, Shinya; Inagawaki, Masaru; Iwagaki, Hiromi

2012-01-01

We analyzed retrospectively the surgical outcomes of diverticular diseases of the colon at the surgical division of Fukuyama Medical Center. Data were collected from 39 patients who underwent surgery for diverticular disease at Fukuyama Medical Center. Thirty-nine patients were admitted between 2005 and 2010. The mean age of the 39 patients was 63.6 years. The collected data included patient demographics, patient history, type of surgery and complications. Patients were divided into 2 groups, Elective vs. Emergent group, right vs. left colon group and laparotomy vs. laparoscopic approach. Multivariate analysis of the logistic model of morbidity revealed a significantly higher rate in the left colon and the Cox proportional hazards model clearly showed fewer postoperative hospital days with the laparoscopic approach. Surgical procedures should be decided in reference to the particular clinical and pathological features of diverticular disease to gain an acceptable morbidity and mortality rates.

Survival pattern of first accident among commercial drivers in the Greater Accra Region of Ghana.

PubMed

Nanga, Salifu; Odai, Nii Afotey; Lotsi, Anani

2017-06-01

In this study, the average accident risk of commercial drivers in the Greater Accra region of Ghana and its associated risks were examined based on a survey data collected using paper-based questionnaires from 204 commercial drivers from the Greater Accra Region of Ghana. The Cox Proportional Hazards Model was used for multivariate analysis while the Kaplan-Meier (KM) Model was used to study the survival patterns of the commercial drivers. The study revealed that the median survival time for an accident to happen is 2.50 years. Good roads provided a better chance of survival than bad roads and experienced drivers have a better chance of survival than the inexperienced drivers. Age of driver, alcohol usage of driver, marital status, condition of road and duration of driver's license were found to be related to the risk of accident. Copyright © 2017 Elsevier Ltd. All rights reserved.

IGFBP6 Regulates Cell Apoptosis and Migration in Glioma.

PubMed

Bei, Yuanqi; Huang, Qingfeng; Shen, Jianhong; Shi, Jinlong; Shen, Chaoyan; Xu, Peng; Chang, Hao; Xia, Xiaojie; Xu, Li; Ji, Bin; Chen, JianGuo

2017-07-01

The insulin-like growth factor binding protein 6 (IGFBP6), as an inhibitor of IGF-II actions, plays an important role in inhibiting survival and migration of tumor cells. In our study, we intended to demonstrate the biological function of IGFBP6 in the development of glioma and its clinical significance. Firstly, Western blot and immunohistochemistry revealed that the expression of IGFBP6 inversely correlated with glioma grade. Secondly, multivariate analysis with the Cox proportional hazards model and Kaplan-Meier analysis indicated that IGFBP6 could be an independent prognostic factor for the survival of glioma patients. In addition, overexpression of IGFBP6 induced glioma cell apoptosis, and depletion of IGFBP6 had the opposite action. Finally, overexpression of IGFBP6 inhibited migration of glioma cells, and depletion of IGFBP6 had the opposite action. Together our findings suggest that IGFBP6 might be an important regulator and prognostic factor for glioma.

Rotating Night-Shift Work and Lung Cancer Risk Among Female Nurses in the United States

PubMed Central

Schernhammer, Eva S.; Feskanich, Diane; Liang, Geyu; Han, Jiali

2013-01-01

The risk of lung cancer among night-shift workers is unknown. Over 20 years of follow-up (1988–2008), we documented 1,455 incident lung cancers among 78,612 women in the Nurses' Health Study. To examine the relationship between rotating night-shift work and lung cancer risk, we used multivariate Cox proportional hazard models adjusted for detailed smoking characteristics and other risk factors. We observed a 28% increased risk of lung cancer among women with 15 or more years spent working rotating night shifts (multivariate relative risk (RR) = 1.28, 95% confidence interval (CI): 1.07, 1.53; Ptrend = 0.03) compared with women who did not work any night shifts. This association was strongest for small-cell lung carcinomas (multivariate RR = 1.56, 95% CI: 0.99, 2.47; Ptrend = 0.03) and was not observed for adenocarcinomas of the lung (multivariate RR = 0.91, 95% CI: 0.67, 1.24; Ptrend = 0.40). Further, the increased risk associated with 15 or more years of rotating night-shift work was limited to current smokers (RR = 1.61, 95% CI: 1.21, 2.13; Ptrend < 0.001), with no association seen in nonsmokers (Pinteraction = 0.03). These results suggest that there are modestly increased risks of lung cancer associated with extended periods of night-shift work among smokers but not among nonsmokers. Though it is possible that this observation was residually confounded by smoking, our findings could also provide evidence of circadian disruption as a “second hit” in the etiology of smoking-related lung tumors. PMID:24049158

Hazard ratio estimation and inference in clinical trials with many tied event times.

PubMed

Mehrotra, Devan V; Zhang, Yiwei

2018-06-13

The medical literature contains numerous examples of randomized clinical trials with time-to-event endpoints in which large numbers of events accrued over relatively short follow-up periods, resulting in many tied event times. A generally common feature across such examples was that the logrank test was used for hypothesis testing and the Cox proportional hazards model was used for hazard ratio estimation. We caution that this common practice is particularly risky in the setting of many tied event times for two reasons. First, the estimator of the hazard ratio can be severely biased if the Breslow tie-handling approximation for the Cox model (the default in SAS and Stata software) is used. Second, the 95% confidence interval for the hazard ratio can include one even when the corresponding logrank test p-value is less than 0.05. To help establish a better practice, with applicability for both superiority and noninferiority trials, we use theory and simulations to contrast Wald and score tests based on well-known tie-handling approximations for the Cox model. Our recommendation is to report the Wald test p-value and corresponding confidence interval based on the Efron approximation. The recommended test is essentially as powerful as the logrank test, the accompanying point and interval estimates of the hazard ratio have excellent statistical properties even in settings with many tied event times, inferential alignment between the p-value and confidence interval is guaranteed, and implementation is straightforward using commonly used software. Copyright © 2018 John Wiley & Sons, Ltd.

Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

PubMed

Kim, Yong Bae; Kim, Gwi Eon; Pyo, Hong Ryull; Cho, Nam Hoon; Keum, Ki Chang; Lee, Chang Geol; Seong, Jinsil; Suh, Chang Ok; Park, Tchan Kyu

2004-11-01

To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types. A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival. Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2-negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2-negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2-negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2-positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2-positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses. In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2-positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.

Repetition of self-harm and suicide following self-harm in children and adolescents: findings from the Multicentre Study of Self-harm in England.

PubMed

Hawton, Keith; Bergen, Helen; Kapur, Navneet; Cooper, Jayne; Steeg, Sarah; Ness, Jennifer; Waters, Keith

2012-12-01

Self-harm (intentional self-poisoning and self-injury) in children and adolescents is often repeated and is associated with increased risk of future suicide. We have investigated factors associated with these outcomes. We used data collected in the Multicentre Study of Self-harm in England on all self-harm hospital presentations by individuals aged 10-18 years between 2000 and 2007, and national death information on these individuals to the end of 2010. Cox hazard proportional models were used to identify independent and multivariable predictors of repetition of self-harm and of suicide. Repetition of self-harm occurred in 27.3% of individuals (N = 3920) who presented between 2000 and 2005 and were followed up until 2007. Multivariate analysis showed that repetition was associated with age, self-cutting, and previous self-harm and psychiatric treatment. Of 51 deaths in individuals who presented between 2000 and 2007 and were followed up to 2010 (N = 5133) half (49.0%) were suicides. The method used was usually different to that used for self-harm. Multivariate analysis showed that suicide was associated with male gender [Hazard ratio (HR) = 2.4, 95% CI 1.2-4.8], self-cutting (HR = 2.1, 95% CI 1.1-3.7) and prior psychiatric treatment at initial presentation (HR = 4.2, 95% CI 1.7-10.5). It was also associated with self-cutting and history of psychiatric treatment at the last episode before death, and history of previous self harm. Self-cutting as a method of self-harm in children and adolescents conveys greater risk of suicide (and repetition) than self-poisoning although different methods are usually used for suicide. The findings underline the need for psychosocial assessment in all cases. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Serum and dietary potassium and risk of incident type 2 diabetes mellitus: The Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Chatterjee, Ranee; Yeh, Hsin-Chieh; Shafi, Tariq; Selvin, Elizabeth; Anderson, Cheryl; Pankow, James S; Miller, Edgar; Brancati, Frederick

2010-10-25

Serum potassium levels affect insulin secretion by pancreatic β-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes mellitus (DM), independent of diuretic use. We analyzed data from 12 209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing prospective cohort study, beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the hazard ratio (HR) of incident DM associated with baseline serum potassium levels. During 9 years of in-person follow-up, 1475 participants developed incident DM. In multivariate analyses, we found an inverse association between serum potassium and risk of incident DM. Compared with those with a high-normal serum potassium level (5.0-5.5 mEq/L), adults with serum potassium levels lower than 4.0 mEq/L, 4.0 to lower than 4.5 mEq/L, and 4.5 to lower than 5.0 mEq/L had an adjusted HR (95% confidence interval [CI]) of incident DM of 1.64 (95% CI, 1.29-2.08), 1.64 (95% CI, 1.34-2.01), and 1.39 (95% CI, 1.14-1.71), respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with HRs of 1.2 to 1.3 for those with a serum potassium level lower than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident DM in unadjusted models but not in multivariate models. Serum potassium level is an independent predictor of incident DM in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of DM.

MicroRNA let-7, T cells, and patient survival in colorectal cancer

PubMed Central

Dou, Ruoxu; Nishihara, Reiko; Cao, Yin; Hamada, Tsuyoshi; Mima, Kosuke; Masuda, Atsuhiro; Masugi, Yohei; Shi, Yan; Gu, Mancang; Li, Wanwan; da Silva, Annacarolina; Nosho, Katsuhiko; Zhang, Xuehong; Meyerhardt, Jeffrey A.; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji

2016-01-01

Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis. Logistic regression analysis and Cox proportional hazards regression were used to assess associations of let-7a (and let-7b) expression (quartile predictor variables) with T-cell densities (binary outcome variables) and mortality, respectively, controlling for tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared with cases in the lowest quartile of let-7a expression, those in the highest quartile were associated with lower densities of CD3+ [multivariate odds ratio (OR), 0.40; 95% confidence interval (CI), 0.23 to 0.67; Ptrend = 0.003] and CD45RO+ cells (multivariate OR, 0.31; 95% CI, 0.17 to 0.58; Ptrend = 0.0004), and higher colorectal cancer-specific mortality (multivariate hazard ratio, 1.82; 95% CI, 1.42 to 3.13; Ptrend = 0.001). In contrast, let-7b expression was not significantly associated with T-cell density or colorectal cancer prognosis. Our data support the role of let-7a in suppressing antitumor immunity in colorectal cancer, and suggest let-7a as a potential target of immunotherapy. PMID:27737877

Stereotactic Body Radiation Therapy and the Influence of Chemotherapy on Overall Survival for Large (≥5 Centimeter) Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Vivek; McMillan, Matthew T.; Grover, Surbhi

2017-01-01

Purpose: Stereotactic body radiation therapy (SBRT) for ≥5 cm lesions is poorly defined, largely owing to the low sample sizes in existing studies. The present analysis examined the SBRT outcomes and assessed the effect of chemotherapy in this population. Methods and Materials: The National Cancer Data Base was queried for primary non-small cell lung cancer ≥5 cm treated with SBRT (≤10 fractions). Patient, tumor, and treatment parameters were extracted. The primary outcome was overall survival (OS). Statistical methods involved Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. Results: From 2004 to 2012, data from 201 patients were analyzed. The median follow-upmore » was 41.1 months. The median tumor size was 5.5 cm (interquartile range 5.0-6.0), with cT2a, cT2b, and cT3 disease in 24.9%, 53.2%, and 21.9%, respectively. The median total SBRT dose and fractionation was 50 Gy in 4 fractions, and 92.5% of the patients underwent SBRT with ≤5 fractions. The median OS was 25.1 months. Of the 201 patients, 15% received chemotherapy. The receipt of chemotherapy was associated with longer OS (median 30.6 vs 23.4 months; P=.027). On multivariable analysis, worse OS was seen with increasing age (hazard ratio [HR] 1.03; P=.012), poorly differentiated tumors (HR 2.06; P=.049), and T3 classification (HR 2.13; P=.005). On multivariable analysis, chemotherapy remained independently associated with improved OS (HR 0.57; P=.039). Conclusions: SBRT has utility in the setting of tumors ≥5 cm, with chemotherapy associated with improved OS in this subset. These hypothesis-generating data now raise the necessity of performing prospective analyses to determine whether chemotherapy confers outcome benefits after SBRT.« less

Impact of heart rate in atrial fibrillation versus sinus rhythm on mortality in octogenarian patients with acute coronary syndrome.

PubMed

Li, Shijun; Barywani, Salim; Fu, Michael

2017-01-01

Association of heart rate (HR) with mortality in patients with acute coronary syndrome (ACS) and aged ≥ 80 years are underrepresented in clinical trials. We therefore aimed to investigate the association of HR in atrial fibrillation (AF) versus sinus rhythm (SR) with all-cause mortality in octogenarian patients with ACS. A total of 336 patients with ACS patients and aged ≥ 80 years were enrolled into the current study. The end point of interest was death from any cause. Association of HR in AF versus SR with mortality was analyzed by Kaplan-Meier curve following log-rank test and multivariable Cox regression analysis. In total, 63 (87.5%) of patients with AF were dead and 147 (59.8%) of patients with SR were dead during the follow-up period. The best cut-off was 80 bpm, with a sensitivity of 62% and specificity of 66%. HR ≤ 80 bpm in SR but not in AF was associated with better outcome as compared with HR > 80 bpm (Chi-Square = 26.55, Log rank P < 0.001). In SR subgroup, the hazard ratios of HR ≤ 80 bpm were 0.51(95% CI 0.37-0.70, P < 0.001) adjusted for age, 0.46 (95%CI 0.33-0.63, P < 0.001) adjusted for gender, 0.62 (95%CI 0.42- 0.93, P = 0.020) adjusted for multivariables respectively. In AF subgroup, the hazard ratios of HR ≤ 80 bpm were 0.83(95% CI 0.49-1.38, P = 0.464) adjusted for age, 0.96 (95%CI 0.59-1.58, P = 0.882) adjusted for gender, 0.72(95% CI 0.41-1.26, P = 0.249) adjusted for multivariables respectively. The current study demonstrates that heart rate is an independent prognostic predictor for all-cause mortality, and HR ≤ 80 bpm is associated with improved outcome in SR but not in AF in octogenarian patients with ACS.

Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors: an international tamoxifen exemestane adjuvant multinational trial analysis.

PubMed

Fontein, Duveken B Y; Seynaeve, Caroline; Hadji, Peyman; Hille, Elysée T M; van de Water, Willemien; Putter, Hein; Kranenbarg, Elma Meershoek-Klein; Hasenburg, Annette; Paridaens, Robert J; Vannetzel, Jean-Michel; Markopoulos, Christos; Hozumi, Yasuo; Bartlett, John M S; Jones, Stephen E; Rea, Daniel William; Nortier, Johan W R; van de Velde, Cornelis J H

2013-06-20

Specific adverse events (AEs) associated with endocrine therapy and related to depletion or blocking of circulating estrogens may be related to treatment efficacy. We investigated the relationship between survival outcomes and specific AEs including vasomotor symptoms (VMSs), musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with breast cancer participating in the international Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Primary efficacy end points were disease-free survival (DFS), overall survival (OS), and distant metastases (DM). VMSs, MSAEs, and VVSs arising in the first year of endocrine treatment were considered. Patients who did not start or who discontinued their allocated therapy and/or had an event (recurrence/death) within 1 year after randomization were excluded. Landmark analyses and time-dependent multivariate Cox proportional hazards models assessed survival differences up to 5 years from the start of treatment. A total of 9,325 patients were included. Patients with specific AEs (v nonspecific or no AEs) had better DFS and OS (multivariate hazard ratio [HR] for DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866]; MSAEs, 0.826 [95% CI, 0.694 to 0.982]; VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for OS: VMSs, 0.583 [95% CI, 0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570 [95% CI, 0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749 [95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not reporting these symptoms. Increasing numbers of specific AEs were also associated with better survival outcomes. Outcomes were unrelated to treatment allocation. Certain specific AEs are associated with superior survival outcomes and may therefore be useful in predicting treatment responses in patients with breast cancer treated with endocrine therapy.

Determinants of birth intervals in Kerala: an application of Cox's hazard model.

PubMed

Nair, S N

1996-01-01

"The present study is an attempt to delineate the differences in the patterns and determinants of birth intervals which appear highly relevant in a transitional population such as Kerala [India]. In this country two comparable surveys, with a period difference of 20 years, were conducted. The study tries to estimate the effects of socio-economic, demographic and proximate variables using Cox's proportional hazard model. For the former data-set, socio-economic variables have [a] significant effect on birth intervals, while for the latter data proximate variables are the significant determinants of birth intervals." (SUMMARY IN ITA AND FRE) excerpt

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

PubMed Central

Gagnon, B; Abrahamowicz, M; Xiao, Y; Beauchamp, M-E; MacDonald, N; Kasymjanova, G; Kreisman, H; Small, D

2010-01-01

Background: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). Methods: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). Results: In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03–1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. Conclusion: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP. PMID:20234363

Prognostic value of the chemokine receptor CXCR4 and epithelial-to-mesenchymal transition in patients with squamous cell carcinoma of the mobile tongue.

PubMed

Albert, Sébastien; Hourseau, Muriel; Halimi, Caroline; Serova, Maria; Descatoire, Véronique; Barry, Béatrix; Couvelard, Anne; Riveiro, Maria Eugenia; Tijeras-Raballand, Annemilaï; de Gramont, Armand; Raymond, Eric; Faivre, Sandrine

2012-12-01

The aim of this study was to evaluate the expression and the prognostic value of chemokine receptor 4 (CXCR4), its cognate ligand the CXCL12, and markers of epithelial-to-mesenchymal transition (EMT) in squamous cell carcinoma (SCC) of the mobile tongue. Patients with primary SCC of the mobile tongue who underwent surgery in our center were screened retrospectively. Patients without prior treatment, who had pre-surgery TNM staging and available tumor samples, were eligible. Protein expression of CXCL12, CXCR4, CA9, E-cadherin, and vimentin was determined by immunohistochemical staining, scored, and correlated with clinical and pathological parameters and overall survival. Multivariate and Cox proportional hazards analyses were performed. Among 160 patients treated and screened, 47 were analyzed. CXCR4 and CXCL12 expression was high in tumor cells. CXCR4 expression in primary tumor samples was significantly higher in patients with high-grade tumors, lymph node metastases, and microscopic nerve invasion (p ≤ 0.05). There was a non-significant trend towards a correlation between high CXCL12 expression and pathologic tumor stage (p=0.07). Tumors with high CXCR4 expression correlated with poor overall survival (hazard ratio=3.6, 95% confidence interval 1.3-9.7; p=0.011), notably in the CXCR4(high)/vimentin-positive subgroup. Vimentin-positive tumors, characterizing EMT, were associated with lower survival (hazard ratio=4.5, 95% confidence interval 1.6-12.3; p=0.0086). Multivariate analysis confirmed vimentin (but not CXCR4) expression as an independent prognostic factor of poor overall survival (p=0.016). Our results suggest that CXCR4 is a marker of tumor aggressiveness and vimentin is an important and independent prognostic factor in patients with SCC of the mobile tongue. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of adherence and persistence among adults with type 2 diabetes mellitus initiating saxagliptin or linagliptin.

PubMed

Farr, Amanda M; Sheehan, John J; Davis, Brian M; Smith, David M

2016-01-01

Adherence and persistence to antidiabetes medications are important to control blood glucose levels among individuals with type 2 diabetes mellitus (T2D). The objective of this study was to compare adherence and persistence over a 12-month period between patients initiating saxagliptin and patients initiating linagliptin, two dipeptidyl peptidase-4 inhibitors. This retrospective cohort study was conducted in MarketScan(®) Commercial and Medicare Supplemental claims databases. Patients with T2D initiating saxagliptin or linagliptin between January 1, 2009, and June 30, 2013, were selected. Patients were required to be at least 18 years old and have 12 months of continuous enrollment prior to and following initiation. Adherence and persistence to initiated medication were measured over the 12 months after initiation using outpatient pharmacy claims. Patients were considered adherent if the proportion of days covered was ≥0.80. Patients were considered nonpersistent (or to have discontinued) if there was a gap of >60 days without initiated medication on hand. Multivariable logistic regression and multivariable Cox proportional hazard models were fit to compare adherence and persistence, respectively, between the two cohorts. There were 21,599 saxagliptin initiators (mean age 55 years; 53% male) and 5,786 linagliptin initiators (mean age 57 years; 54% male) included in the study sample. Over the 12-month follow-up, 46% of saxagliptin initiators and 42% of linagliptin initiators were considered adherent and 47% of saxagliptin initiators and 51% of linagliptin initiators discontinued their initiated medication. After controlling for patient characteristics, saxagliptin initiation was associated with significantly greater odds of being adherent (adjusted odds ratio =1.212, 95% CI 1.140-1.289) and significantly lower hazards of discontinuation (adjusted hazard ratio =0.887, 95% CI 0.850-0.926) compared with linagliptin initiation. Compared with patients with T2D who initiated linagliptin, patients with T2D who initiated saxagliptin had significantly better adherence and persistence.

Right retroperitoneoscopic living donor nephrectomy does not increase surgical complications in the recipient and leads to excellent long-term outcome.

PubMed

Schaumeier, Maria Johanna; Nagy, Alexandra; Dell-Kuster, Salome; Rosenthal, Rachel; Schaub, Stefan; Dickenmann, Michael; Gurke, Lorenz; Wolff, Thomas

2017-09-05

Right-sided retroperitoneoscopic living donor nephrectomy (LDN) has been shown to be safe for the donor but it is unknown whether the short renal vein is associated with complications or an impaired long-term outcome in the recipient. In this retrospective cohort study, consecutive transplant recipients after retroperitoneoscopic LDN were enrolled. Complications occurring within 1 year were classified according to the Clavien-Dindo Classification for Surgical Complications and analysed using multivariable logistic regression. Predictors of 1-year creatinine clearance were analysed with multivariable linear regression. Cox proportional hazard models were used to analyse graft survival. Of the 251 recipients, 193 (77%) received a left kidney and 58 (23%) a right kidney. Surgical complications of Clavien-Dindo grade 3 or higher were comparable in recipients of right and left kidneys (33% vs 29%, odds ratio 0.98, 95% confidence interval [CI] 0.50, 1.94). The occurrence of a surgical complication had a significant impact on creatinine clearance at 1 year (decrease of 6 ml/min/m2, p = 0.016). Vascular complications in right kidneys were more common but were all corrected without impact on graft survival. One-year graft-survival was similar in recipients of right (98.3%) and left (96.9%) kidneys, as was creatinine clearance one year after transplantation (mean difference 3.3 ml/min/m2, 95% CI -1.5, 8.1; p = 0.175). After a median follow-up of 5 years, neither the side (hazard ratio 1.56, 95% CI 0.67, 3.63) nor surgical complications (hazard ratio 1.44, 95% CI 0.65, 3.19) were associated with graft failure. Right retroperitoneoscopic LDN does not compromise the outcome of transplantation. Surgical complications, long-term graft function and graft survival were comparable in right and left kidneys.

Cumulative HIV viremia and non-AIDS-defining malignancies among a sample of HIV-infected male veterans.

PubMed

Kowalkowski, Marc A; Day, Rena S; Du, Xianglin L; Chan, Wenyaw; Chiao, Elizabeth Y

2014-10-01

Research suggests that cumulative measurement of HIV exposure is associated with mortality, AIDS, and AIDS-defining malignancies. However, the relationship between cumulative HIV and non-AIDS-defining malignancies (NADMs) remains unclear. The aim of this study was to evaluate the effect of different HIV measures on NADM hazard among HIV-infected male veterans. We performed a retrospective cohort study using Veterans Affairs HIV Clinical Case Registry data from 1985 to 2010. We analyzed the relationship between HIV exposure (recent HIV RNA, % undetectable HIV RNA, and HIV copy-years viremia) and NADM. To evaluate the effect of HIV, we calculated hazard ratios for 3 common virally associated NADM [ie, hepatocarcinoma (HCC), Hodgkin lymphoma (HL), and squamous cell carcinoma of the anus (SCCA)] in multivariable Cox regression models. Among 31,576 HIV-infected male veterans, 383 HCC, 211 HL, and 373 SCCA cases were identified. In multivariable regression models, cross-sectional HIV measurement was not associated with NADM. However, compared with <20% undetectable HIV, individuals with ≥80% had decreased HL [adjusted hazard ratio (aHR) = 0.62; 95% confidence interval (CI): 0.37 to 1.02] and SCCA (aHR = 0.64; 95% CI: 0.44 to 0.93). Conversely, each log10 increase in HIV copy-years was associated with elevated HL (aHR = 1.22; 95% CI: 1.06 to 1.40) and SCCA (aHR = 1.36; 95% CI: 1.21 to 1.52). Model fit was best with HIV copy-years. Cumulative HIV was not associated with HCC. Cumulative HIV was associated with certain virally associated NADM (ie, HL and SCCA), independent of measured covariates. Findings underline the importance of early treatment initiation and durable medication adherence to reduce cumulative HIV burden. Future research should prioritize how to best apply cumulative HIV measures in screening for these cancers.

Oncologic relevance of magnetic resonance imaging-detected threatened mesorectal fascia for patients with mid or low rectal cancer: A longitudinal analysis before and after long-course, concurrent chemoradiotherapy.

PubMed

Son, Il Tae; Kim, Young Hoon; Lee, Kyoung Ho; Kang, Sung Il; Kim, Duck-Woo; Shin, Eun; Lee, Keun-Wook; Ahn, Soyeon; Kim, Jae-Sung; Kang, Sung-Bum

2017-07-01

The oncologic importance of threatened mesorectal fascia detected with magnetic resonance imaging is obscured by the heterogeneity of preoperative treatments. We evaluated the oncologic relevance of threatened mesorectal fascia detected with consecutive magnetic resonance imaging performed before and after long-course, concurrent chemoradiotherapy (LCRT) for mid or low rectal cancer. We evaluated 196 patients who underwent total mesorectal excision with LCRT. Threatened mesorectal fascia was defined as a shortest distance from tumor to mesorectal fascia of ≤ 1 mm on magnetic resonance imaging. Multivariate analyses for disease-free survival using magnetic resonance imaging-based parameters were conducted with a Cox proportional hazard model before and after LCRT, respectively. The pathologic positivity of the circumferential resection margin was greater for threatened mesorectal fascia than for clear mesorectal fascia (pre-LCRT, 14.8% vs 3.0%, P = .004; post-LCRT, 15.4% vs 4.5%, P = .025). At a median follow-up of 68 months, 3-year disease-free survival was worse for threatened mesorectal fascia than for clear mesorectal fascia (pre-LCRT, 77.0% vs 88.1%, P = .023; post-LCRT, 76.9% vs 86.6%, P = .029). On multivariate analyses, threatened mesorectal fascia on pre-LCRT magnetic resonance imaging was an independent factor for poor disease-free survival (hazard ratio = 2.153, 95% confidence interval, 1.07-4.32, P = .031), whereas threatened mesorectal fascia on post-LCRT magnetic resonance imaging was not (hazard ratio = 1.689, 95% confidence interval, 0.77-3.66, P = .189). This study confirms that magnetic resonance imaging-detected threatened mesorectal fascia predicts poor oncologic outcomes for mid or low rectal cancer and shows that the diagnostic performance of pre-LCRT magnetic resonance imaging is different from that of post-LCRT magnetic resonance imaging. Copyright © 2017 Elsevier Inc. All rights reserved.

Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucas, John T., E-mail: jolucas@wakehealth.edu; Colmer, Hentry G.; White, Lance

Purpose: To estimate the hazard for neurologic (central nervous system, CNS) and nonneurologic (non-CNS) death associated with patient, treatment, and systemic disease status in patients receiving stereotactic radiosurgery after whole-brain radiation therapy (WBRT) failure, using a competing risk model. Patients and Methods: Of 757 patients, 293 experienced recurrence or new metastasis following WBRT. Univariate Cox proportional hazards regression identified covariates for consideration in the multivariate model. Competing risks multivariable regression was performed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for both CNS and non-CNS death after adjusting for patient, disease, and treatment factors. The resultantmore » model was converted into an online calculator for ease of clinical use. Results: The cumulative incidence of CNS and non-CNS death at 6 and 12 months was 20.6% and 21.6%, and 34.4% and 35%, respectively. Patients with melanoma histology (relative to breast) (aHR 2.7, 95% CI 1.5-5.0), brainstem location (aHR 2.1, 95% CI 1.3-3.5), and number of metastases (aHR 1.09, 95% CI 1.04-1.2) had increased aHR for CNS death. Progressive systemic disease (aHR 0.55, 95% CI 0.4-0.8) and increasing lowest margin dose (aHR 0.97, 95% CI 0.9-0.99) were protective against CNS death. Patients with lung histology (aHR 1.3, 95% CI 1.1-1.9) and progressive systemic disease (aHR 2.14, 95% CI 1.5-3.0) had increased aHR for non-CNS death. Conclusion: Our nomogram provides individual estimates of neurologic death after salvage stereotactic radiosurgery for patients who have failed prior WBRT, based on histology, neuroanatomical location, age, lowest margin dose, and number of metastases after adjusting for their competing risk of death from other causes.« less

Association between bilirubin and mode of death in severe systolic heart failure.

PubMed

Wu, Audrey H; Levy, Wayne C; Welch, Kathleen B; Neuberg, Gerald W; O'Connor, Christopher M; Carson, Peter E; Miller, Alan B; Ghali, Jalal K

2013-04-15

The bilirubin level has been associated with worse outcomes, but it has not been studied as a predictor for the mode of death in patients with systolic heart failure. The Prospective Randomized Amlodipine Evaluation Study (PRAISE) cohort (including New York Heart Association class IIIB-IV patients with left ventricular ejection fraction <30%, n = 1,135) was analyzed, divided by bilirubin level: ≤0.6 mg/dl, group 1; >0.6 to 1.2 mg/dl, group 2; and >1.2 mg/dl, group 3. Multivariate Cox proportional hazards models were used to determine the association of bilirubin with the risk of sudden or pump failure death. Total bilirubin was entered as a base 2 log-transformed variable (log2 bilirubin), indicating doubling of the bilirubin level corresponding to each increase in variable value. The higher bilirubin groups had a lower ejection fraction (range 19% to 21%), sodium (range 138 to 139 mmol/L), and systolic blood pressure (range 111 to 120 mm Hg), a greater heart rate (range 79 to 81 beats/min), and greater diuretic dosages (range 86 to 110 furosemide-equivalent total daily dose in mg). The overall survival rates declined with increasing bilirubin (24.3, 31.3, and 44.3 deaths per 100 person-years, respectively, for groups 1, 2, and 3). Although a positive relation was seen between log2 bilirubin and both pump failure risk and sudden death risk, the relation in multivariate modeling was significant only for pump failure mortality (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82, p = 0.0004), not for sudden death mortality (hazard ratio 1.21, 95% confidence interval 0.98 to 1.49, p = 0.08). In conclusion, an increasing bilirubin level was significantly associated with the risk of pump failure death but not for sudden death in patients with severe systolic heart failure. Copyright © 2013 Elsevier Inc. All rights reserved.

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, Kristin A., E-mail: kristin.higgins@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; O'Connell, Kelli

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822more » patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.« less

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

PubMed

Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

2017-07-01

The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Statins use and risk of new-onset diabetes in hypertensive patients: a population-based retrospective cohort study in Yinzhou district, Ningbo city, People's Republic of China.

PubMed

Li, Hailong; Lin, Hongbo; Zhao, Houyu; Xu, Yang; Cheng, Yinchu; Shen, Peng; Zhan, Siyan

2018-01-01

Reports have suggested that statin use is associated with an increased incidence of type 2 diabetes mellitus (T2DM). Guidelines suggested that statins should be prescribed in hypertensive patients for primary prevention. However, there were very few studies on the risk of T2DM associated with statin use among patients with hypertension in mainland People's Republic of China. To determine the association between statin use and new-onset diabetes mellitus among patients with hypertension in mainland People's Republic of China. We performed a retrospective cohort study of hypertensive patients using the Yinzhou regional health care database from January 1, 2010, to August 31, 2016. Patients aged 30-90 years old without T2DM were eligible for inclusion. We identified new statin initiators and nonusers by using prescription records of inpatients and outpatients. Multivariate Cox model and propensity score methods were used to adjust potential confounders, including age, sex, body mass index, comorbidities, lifestyle characteristics, and baseline antihypertensive drug use. The risk of incident T2DM among statin initiators compared to nonusers was estimated by the Cox proportional hazards model. Propensity scores for statin use were then developed using logistic regression, statin initiators were matched 1:1 with nonusers according to propensity scores with the nearest neighbor matching method within 0.2 caliper width, and Cox regression was again conducted. Among 67,993 patients (21,551 statin initiators; 46,442 nonusers), the unadjusted incidence rate of incident T2DM was higher in statin initiators than nonusers (25.68 versus 14.19 events/1,000 person-years; adjusted hazard ratio: 1.55; 95% confidence interval: 1.44-1.66). After propensity score 1:1 matching (19,818 statin initiators; 19,818 nonusers), baseline characteristics between 2 groups were balanced except that the nonusers group was 0.53 years older on average ( P <0.001). Then statin use was still associated with a significant increased risk for T2DM in the matched cohort (adjusted hazard ratio: 1.54; 95% confidence interval: 1.41-1.67). Subgroup analyses also demonstrated similar findings. Our study indicated an association between statin use and an increased risk of new-onset diabetes mellitus. It provides better understanding of statin and new-onset diabetes mellitus association among hypertensive patients in real-word setting. As an observational study, our findings were prone to unmeasured confounding and bias.

Association of Modality with Mortality among Canadian Aboriginals

PubMed Central

Hemmelgarn, Brenda; Rigatto, Claudio; Komenda, Paul; Yeates, Karen; Promislow, Steven; Mojica, Julie; Tangri, Navdeep

2012-01-01

Summary Background and objectives Previous studies have shown that Aboriginals and Caucasians experience similar outcome on dialysis in Canada. Using the Canadian Organ Replacement Registry, this study examined whether dialysis modality (peritoneal or hemodialysis) impacted mortality in Aboriginal patients. Design, setting, participants, & measurements This study identified 31,576 adult patients (hemodialysis: Aboriginal=1839, Caucasian=21,430; peritoneal dialysis: Aboriginal=554, Caucasian=6769) who initiated dialysis between January of 2000 and December of 2009. Aboriginal status was identified by self-report. Dialysis modality was determined 90 days after dialysis initiation. Multivariate Cox proportional hazards and competing risk models were constructed to determine the association between race and mortality by dialysis modality. Results During the study period, 939 (51.1%) Aboriginals and 12,798 (53.3%) Caucasians initiating hemodialysis died, whereas 166 (30.0%) and 2037 (30.1%), respectively, initiating peritoneal dialysis died. Compared with Caucasians, Aboriginals on hemodialysis had a comparable risk of mortality (adjusted hazards ratio=1.04, 95% confidence interval=0.96–1.11, P=0.37). However, on peritoneal dialysis, Aboriginals experienced a higher risk of mortality (adjusted hazards ratio=1.36, 95% confidence interval=1.13–1.62, P=0.001) and technique failure (adjusted hazards ratio=1.29, 95% confidence interval=1.03–1.60, P=0.03) than Caucasians. The risk of technique failure varied by patient age, with younger Aboriginals (<50 years old) more likely to develop technique failure than Caucasians (adjusted hazards ratio=1.76, 95% confidence interval=1.23–2.52, P=0.002). Conclusions Aboriginals on peritoneal dialysis experience higher mortality and technique failure relative to Caucasians. Reasons for this race disparity in peritoneal dialysis outcomes are unclear. PMID:22997343

Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study.

PubMed

Olsen, Anne-Marie Schjerning; Fosbøl, Emil L; Lindhardsen, Jesper; Folke, Fredrik; Charlot, Mette; Selmer, Christian; Bjerring Olesen, Jonas; Lamberts, Morten; Ruwald, Martin H; Køber, Lars; Hansen, Peter R; Torp-Pedersen, Christian; Gislason, Gunnar H

2012-10-16

The cardiovascular risk after the first myocardial infarction (MI) declines rapidly during the first year. We analyzed whether the cardiovascular risk associated with using nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with the time elapsed following first-time MI. We identified patients aged 30 years or older admitted with first-time MI in 1997 to 2009 and subsequent NSAID use by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. We calculated the incidence rates of death and a composite end point of coronary death or nonfatal recurrent MIs associated with NSAID use in 1-year time intervals up to 5 years after inclusion and analyzed risk by using multivariable adjusted time-dependent Cox proportional hazards models. Of the 99 187 patients included, 43 608 (44%) were prescribed NSAIDs after the index MI. There were 36 747 deaths and 28 693 coronary deaths or nonfatal recurrent MIs during the 5 years of follow-up. Relative to noncurrent treatment with NSAIDs, the use of any NSAID in the years following MI was persistently associated with an increased risk of death (hazard ratio 1.59 [95% confidence interval, 1.49-1.69]) after 1 year and hazard ratio 1.63 [95% confidence interval, 1.52-1.74] after 5 years) and coronary death or nonfatal recurrent MI (hazard ratio, 1.30 [95% confidence interval,l 1.22-1.39] and hazard ratio, 1.41 [95% confidence interval, 1.28-1.55]). The use of NSAIDs is associated with persistently increased coronary risk regardless of time elapsed after first-time MI. We advise long-term caution in the use of NSAIDs for patients after MI.

Mining gene link information for survival pathway hunting.

PubMed

Jing, Gao-Jian; Zhang, Zirui; Wang, Hong-Qiang; Zheng, Hong-Mei

2015-08-01

This study proposes a gene link-based method for survival time-related pathway hunting. In this method, the authors incorporate gene link information to estimate how a pathway is associated with cancer patient's survival time. Specifically, a gene link-based Cox proportional hazard model (Link-Cox) is established, in which two linked genes are considered together to represent a link variable and the association of the link with survival time is assessed using Cox proportional hazard model. On the basis of the Link-Cox model, the authors formulate a new statistic for measuring the association of a pathway with survival time of cancer patients, referred to as pathway survival score (PSS), by summarising survival significance over all the gene links in the pathway, and devise a permutation test to test the significance of an observed PSS. To evaluate the proposed method, the authors applied it to simulation data and two publicly available real-world gene expression data sets. Extensive comparisons with previous methods show the effectiveness and efficiency of the proposed method for survival pathway hunting.

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups.

PubMed

Bosse, Tjalling; Nout, Remi A; McAlpine, Jessica N; McConechy, Melissa K; Britton, Heidi; Hussein, Yaser R; Gonzalez, Carlene; Ganesan, Raji; Steele, Jane C; Harrison, Beth T; Oliva, Esther; Vidal, August; Matias-Guiu, Xavier; Abu-Rustum, Nadeem R; Levine, Douglas A; Gilks, C Blake; Soslow, Robert A

2018-05-01

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.

Outcomes for Spine Stereotactic Body Radiation Therapy and an Analysis of Predictors of Local Recurrence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, Andrew J.; Tao, Randa; Rebueno, Neal C.

Purpose: To investigate local control, survival outcomes, and predictors of local relapse for patients treated with spine stereotactic body radiation therapy. Methods and Materials: We reviewed the records of 332 spinal metastases consecutively treated with stereotactic body radiation therapy between 2002 and 2012. The median follow-up for all living patients was 33 months (range, 0-111 months). Endpoints were overall survival and local control (LC); recurrences were classified as either in-field or marginal. Results: The 1-year actuarial LC and overall survival rates were 88% and 64%, respectively. Patients with local relapses had poorer dosimetric coverage of the gross tumor volume (GTV) compared withmore » patients without recurrence (minimum dose [Dmin] biologically equivalent dose [BED] 23.9 vs 35.1 Gy, P<.001; D98 BED 41.8 vs 48.1 Gy, P=.001; D95 BED 47.2 vs 50.5 Gy, P=.004). Furthermore, patients with marginal recurrences had poorer prescription coverage of the GTV (86% vs 93%, P=.01) compared with those with in-field recurrences, potentially because of more upfront spinal canal disease (78% vs 24%, P=.001). Using a Cox regression univariate analysis, patients with a GTV BED Dmin ≥33.4 Gy (median dose) (equivalent to 14 Gy in 1 fraction) had a significantly higher 1-year LC rate (94% vs 80%, P=.001) compared with patients with a lower GTV BED Dmin; this factor was the only significant variable on multivariate Cox analysis associated with LC (P=.001, hazard ratio 0.29, 95% confidence interval 0.14-0.60) and also was the only variable significant in a separate competing risk multivariate model (P=.001, hazard ratio 0.30, 95% confidence interval 0.15-0.62). Conclusions: Stereotactic body radiation therapy offers durable control for spinal metastases, but there is a subset of patients that recur locally. Patients with local relapse had significantly poorer tumor coverage, which was likely attributable to treatment planning directives that prioritized the spinal cord constraints over tumor coverage. When possible, we recommend maintaining a GTV Dmin above 14 Gy in 1 fraction and 21 Gy in 3 fractions.« less

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data.

PubMed

Ching, Travers; Zhu, Xun; Garmire, Lana X

2018-04-01

Artificial neural networks (ANN) are computing architectures with many interconnections of simple neural-inspired computing elements, and have been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosis from high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet achieves the same or better predictive accuracy compared to other methods, including Cox-proportional hazards regression (with LASSO, ridge, and mimimax concave penalty), Random Forests Survival and CoxBoost. Cox-nnet also reveals richer biological information, at both the pathway and gene levels. The outputs from the hidden layer node provide an alternative approach for survival-sensitive dimension reduction. In summary, we have developed a new method for accurate and efficient prognosis prediction on high throughput data, with functional biological insights. The source code is freely available at https://github.com/lanagarmire/cox-nnet.

Meat, eggs, dairy products, and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

PubMed

Pala, Valeria; Krogh, Vittorio; Berrino, Franco; Sieri, Sabina; Grioni, Sara; Tjønneland, Anne; Olsen, Anja; Jakobsen, Marianne Uhre; Overvad, Kim; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Romieu, Isabelle; Linseisen, Jakob; Rohrmann, Sabine; Boeing, Heiner; Steffen, Annika; Trichopoulou, Antonia; Benetou, Vassiliki; Naska, Androniki; Vineis, Paolo; Tumino, Rosario; Panico, Salvatore; Masala, Giovanna; Agnoli, Claudia; Engeset, Dagrun; Skeie, Guri; Lund, Eiliv; Ardanaz, Eva; Navarro, Carmen; Sánchez, Maria-José; Amiano, Pilar; Svatetz, Carlos Alberto Gonzalez; Rodriguez, Laudina; Wirfält, Elisabet; Manjer, Jonas; Lenner, Per; Hallmans, Göran; Peeters, Petra H M; van Gils, Carla H; Bueno-de-Mesquita, H Bas; van Duijnhoven, Fränzel J B; Key, Timothy J; Spencer, Elizabeth; Bingham, Sheila; Khaw, Kay-Tee; Ferrari, Pietro; Byrnes, Graham; Rinaldi, Sabina; Norat, Teresa; Michaud, Dominique S; Riboli, Elio

2009-09-01

A Western diet is associated with breast cancer risk. We investigated the relation of meat, egg, and dairy product consumption with breast cancer risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Between 1992 and 2003, information on diet was collected from 319,826 women. Disease hazard ratios were estimated with multivariate Cox proportional hazard models. Breast cancer cases (n = 7119) were observed during 8.8 y (median) of follow-up. No consistent association was found between breast cancer risk and the consumption of any of the food groups under study, when analyzed by both categorical and continuous exposure variable models. High processed meat consumption was associated with a modest increase in breast cancer risk in the categorical model (hazard ratio: 1.10; 95% CI: 1.00, 1.20; highest compared with lowest quintile: P for trend = 0.07). Subgroup analyses suggested an association with butter consumption, limited to premenopausal women (hazard ratio: 1.28; 95% CI: 1.06, 1.53; highest compared with lowest quintile: P for trend = 0.21). Between-country heterogeneity was found for red meat (Q statistic = 18.03; P = 0.05) and was significantly explained (P = 0.023) by the proportion of meat cooked at high temperature. We have not consistently identified intakes of meat, eggs, or dairy products as risk factors for breast cancer. Future studies should investigate the possible role of high-temperature cooking in the relation of red meat intake with breast cancer risk.

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma

PubMed Central

Nerich, Virginie; Hugues, Marion; Paillard, Marie Justine; Borowski, Laëtitia; Nai, Thierry; Stein, Ulrich; Nguyen Tan Hon, Thierry; Montcuquet, Philippe; Maurina, Tristan; Mouillet, Guillaume; Kleinclauss, François; Pivot, Xavier; Limat, Samuel; Thiery-Vuillemin, Antoine

2014-01-01

Introduction The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. Patients and methods All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. Results For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13–22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22–0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31–0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22–0.82], P=0.002). Median OS was 21 months [14–29 months] for patients who received at least one targeted therapy compared with 12 months [7–15 months] for patients who were treated only by immunotherapy agents (P=0.003). Conclusion Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications. PMID:24600236

Marital status and survival in patients with rectal cancer: A population-based STROBE cohort study.

PubMed

Li, Zhuyue; Wang, Kang; Zhang, Xuemei; Wen, Jin

2018-05-01

To examine the impact of marital status on overall survival (OS) and rectal cancer-specific survival (RCSS) for aged patients.We used the Surveillance, Epidemiology and End Results database to identify aged patients (>65 years) with early stage rectal cancer (RC) (T1-T4, N0, M0) in the United States from 2004 to 2010. Propensity score matching was conducted to avoid potential confounding factors with ratio at 1:1. We used Kaplan-Meier to compare OS and RCSS between the married patients and the unmarried, respectively. We used cox proportion hazard regressions to obtain hazard rates for OS, and proportional subdistribution hazard model was performed to calculate hazard rates for RCSS.Totally, 5196 patients were included. The married (2598 [50%]) aged patients had better crude 5-year overall survival rate (64.2% vs 57.3%, P < .001) and higher crude 5-year cancer-specific survival rate (80% vs 75.9%, P < .001) than the unmarried (2598 (50%)), respectively. In multivariate analyses, married patients had significantly lower overall death than unmarried patients (HR = 0.77, 95% CI = 0.71-0.83, P < .001), while aged married patients had no cancer-specific survival benefit versus the unmarried aged patients (HR = 0.92, 95% CI = 0.81-1.04, P = .17).Among old population, married patients with early stage RC had better OS than the unmarried, while current evidence showed that marital status might have no protective effect on cancer-specific survival.

Herpes zoster correlates with pyogenic liver abscesses in Taiwan.

PubMed

Mei-Ling, Shen; Kuan-Fu, Liao; Sung-Mao, Tsai; Cheng-Li, Lin Ms; Shih-Wei, Lai

2016-12-01

The purpose of the paper was to explore the relationship between herpes zoster and pyogenic liver abscesses in Taiwan. This was a nationwide cohort study. Using the database of the Taiwan National Health Insurance Program, there were 33049 subjects aged 20-84 years who were newly diagnosed with herpes zoster from 1998 to 2010 that were selected for our study, and they were our herpes zoster group. 131707 randomly selected subjects without herpes zoster were our non-herpes zoster group. Both groups were matched by sex, age, other comorbidities, and the index year of their herpes zoster diagnosis. The incidence of pyogenic liver abscesses at the end of 2011 was then estimated. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratio and 95% confidence interval for pyogenic liver abscesses associated with herpes zoster and other comorbidities. The overall incidence rate was 1.38-fold higher in the herpes zoster group than in the non-herpes zoster group (4.47 vs. 3.25 per 10000 person-years, 95% confidence interval 1.32, 1.44). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscesses was 1.34 in the herpes zoster group (95% confidence interval 1.05, 1.72) when compared with the non-herpes zoster group. Sex (in this case male), age, presence of biliary stones, chronic kidney diseases, chronic liver diseases, cancers, and diabetes mellitus were also significantly associated with pyogenic liver abscesses. Patients with herpes zoster are associated with an increased hazard of developing pyogenic liver abscesses.

Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multiethnic Urban Population: The Northern Manhattan Study.

PubMed

Willey, Joshua; Gardener, Hannah; Cespedes, Sandino; Cheung, Ying K; Sacco, Ralph L; Elkind, Mitchell S V

2017-11-01

There is growing evidence that increased dietary sodium (Na) intake increases the risk of vascular diseases, including stroke, at least in part via an increase in blood pressure. Higher dietary potassium (K), seen with increased intake of fruits and vegetables, is associated with lower blood pressure. The goal of this study was to determine the association of a dietary Na:K with risk of stroke in a multiethnic urban population. Stroke-free participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were followed-up for incident stroke. Baseline food frequency questionnaires were analyzed for Na and K intake. We estimated the hazard ratios and 95% confidence intervals for the association of Na:K with incident total stroke using multivariable Cox proportional hazards models. Among 2570 participants with dietary data (mean age, 69±10 years; 64% women; 21% white; 55% Hispanic; 24% black), the mean Na:K ratio was 1.22±0.43. Over a mean follow-up of 12 years, there were 274 strokes. In adjusted models, a higher Na:K ratio was associated with increased risk for stroke (hazard ratio, 1.6; 95% confidence interval, 1.2-2.1) and specifically ischemic stroke (hazard ratio, 1.6; 95% confidence interval, 1.2-2.1). Na:K intake is an independent predictor of stroke risk. Further studies are required to understand the joint effect of Na and K intake on risk of cardiovascular disease. © 2017 American Heart Association, Inc.

Association between GFR Estimated by Multiple Methods at Dialysis Commencement and Patient Survival

PubMed Central

Wong, Muh Geot; Pollock, Carol A.; Cooper, Bruce A.; Branley, Pauline; Collins, John F.; Craig, Jonathan C.; Kesselhut, Joan; Luxton, Grant; Pilmore, Andrew; Harris, David C.

2014-01-01

Summary Background and objectives The Initiating Dialysis Early and Late study showed that planned early or late initiation of dialysis, based on the Cockcroft and Gault estimation of GFR, was associated with identical clinical outcomes. This study examined the association of all-cause mortality with estimated GFR at dialysis commencement, which was determined using multiple formulas. Design, setting, participants, & measurements Initiating Dialysis Early and Late trial participants were stratified into tertiles according to the estimated GFR measured by Cockcroft and Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease-Epidemiology Collaboration formula at dialysis commencement. Patient survival was determined using multivariable Cox proportional hazards model regression. Results Only Initiating Dialysis Early and Late trial participants who commenced on dialysis were included in this study (n=768). A total of 275 patients died during the study. After adjustment for age, sex, racial origin, body mass index, diabetes, and cardiovascular disease, no significant differences in survival were observed between estimated GFR tertiles determined by Cockcroft and Gault (lowest tertile adjusted hazard ratio, 1.11; 95% confidence interval, 0.82 to 1.49; middle tertile hazard ratio, 1.29; 95% confidence interval, 0.96 to 1.74; highest tertile reference), Modification of Diet in Renal Disease (lowest tertile hazard ratio, 0.88; 95% confidence interval, 0.63 to 1.24; middle tertile hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; highest tertile reference), and Chronic Kidney Disease-Epidemiology Collaboration equations (lowest tertile hazard ratio, 0.93; 95% confidence interval, 0.67 to 1.27; middle tertile hazard ratio, 1.15; 95% confidence interval, 0.86 to 1.54; highest tertile reference). Conclusion Estimated GFR at dialysis commencement was not significantly associated with patient survival, regardless of the formula used. However, a clinically important association cannot be excluded, because observed confidence intervals were wide. PMID:24178976

Is copeptin level associated with 1-year mortality after out-of-hospital cardiac arrest? Insights from the Paris registry*.

PubMed

Geri, Guillaume; Dumas, Florence; Chenevier-Gobeaux, Camille; Bouglé, Adrien; Daviaud, Fabrice; Morichau-Beauchant, Tristan; Jouven, Xavier; Mira, Jean-Paul; Pène, Frédéric; Empana, Jean-Philippe; Cariou, Alain

2015-02-01

The availability of circulating biomarkers that helps to identify early out-of-hospital cardiac arrest survivors who are at increased risk of long-term mortality remains challenging. Our aim was to prospectively study the association between copeptin and 1-year mortality in patients with out-of-hospital cardiac arrest admitted in a tertiary cardiac arrest center. Retrospective monocenter study. Tertiary cardiac arrest center in Paris, France. Copeptin was assessed at admission and day 3. Pre- and intrahospital factors associated with 1-year mortality were analyzed by multivariate Cox proportional analysis. None. Two hundred ninety-eight consecutive out-of-hospital cardiac arrest patients (70.3% male; median age, 60.2 yr [49.9-71.4]) were admitted in a tertiary cardiac arrest center in Paris (France). After multivariate analysis, higher admission copeptin was associated with 1-year mortality with a threshold effect (hazard ratio(5th vs 1st quintile) = 1.64; 95% CI, 1.05-2.58; p = 0.03). Day 3 copeptin was associated with 1-year mortality in a dose-dependent manner (hazard ratio(2nd vs 1st quintile) = 1.87; 95% CI, 1.00-3.49; p = 0.05; hazard ratio(3rd vs 1st quintile) = 1.92; 95% CI, 1.02-3.64; p = 0.04; hazard ratio(4th vs 1st quintile) = 2.12; 95% CI, 1.14-3.93; p = 0.02; and hazard ratio(5th vs 1st quintile) = 2.75; 95% CI, 1.47-5.15; p < 0.01; p for trend < 0.01). For both admission and day 3 copeptin, association with 1-year mortality existed for out-of-hospital cardiac arrest of cardiac origin only (p for interaction = 0.05 and < 0.01, respectively). When admission and day 3 copeptin were mutually adjusted, only day 3 copeptin remained associated with 1-year mortality in a dose-dependent manner (p for trend = 0.01). High levels of copeptin were associated with 1-year mortality independently from prehospital and intrahospital risk factors, especially in out-of-hospital cardiac arrest of cardiac origin. Day 3 copeptin was superior to admission copeptin: this could permit identification of out-of-hospital cardiac arrest survivors at increased risk of mortality and allow for close observation of such patients.

[Use of multiple regression models in observational studies (1970-2013) and requirements of the STROBE guidelines in Spanish scientific journals].

PubMed

Real, J; Cleries, R; Forné, C; Roso-Llorach, A; Martínez-Sánchez, J M

In medicine and biomedical research, statistical techniques like logistic, linear, Cox and Poisson regression are widely known. The main objective is to describe the evolution of multivariate techniques used in observational studies indexed in PubMed (1970-2013), and to check the requirements of the STROBE guidelines in the author guidelines in Spanish journals indexed in PubMed. A targeted PubMed search was performed to identify papers that used logistic linear Cox and Poisson models. Furthermore, a review was also made of the author guidelines of journals published in Spain and indexed in PubMed and Web of Science. Only 6.1% of the indexed manuscripts included a term related to multivariate analysis, increasing from 0.14% in 1980 to 12.3% in 2013. In 2013, 6.7, 2.5, 3.5, and 0.31% of the manuscripts contained terms related to logistic, linear, Cox and Poisson regression, respectively. On the other hand, 12.8% of journals author guidelines explicitly recommend to follow the STROBE guidelines, and 35.9% recommend the CONSORT guideline. A low percentage of Spanish scientific journals indexed in PubMed include the STROBE statement requirement in the author guidelines. Multivariate regression models in published observational studies such as logistic regression, linear, Cox and Poisson are increasingly used both at international level, as well as in journals published in Spanish. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX).

PubMed

Burgos, P I; Vilá, L M; Reveille, J D; Alarcón, G S

2009-12-01

To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16-87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01-1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09-1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10-1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07-5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival.

Confounder summary scores when comparing the effects of multiple drug exposures.

PubMed

Cadarette, Suzanne M; Gagne, Joshua J; Solomon, Daniel H; Katz, Jeffrey N; Stürmer, Til

2010-01-01

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.

Coffee, caffeine, and risk of completed suicide: results from 3 prospective cohorts of American adults

PubMed Central

Lucas, Michel; O’Reilly, Eilis J.; Pan, An; Mirzaei, Fariba; Willett, Walter C.; Okereke, Olivia I.; Ascherio, Alberto

2014-01-01

Objective To evaluate the association between coffee and caffeine consumption and suicide risk in three large-scale cohorts of U.S. men and women. Methods We accessed data of 43,599 men enrolled in the Health Professionals Follow-up Study (HPFS, 1988–2008), 73,820 women in the Nurses’ Health Study (NHS, 1992–2008), and 91,005 women in the NHS II (1993–2007). Consumption of caffeine, coffee, and decaffeinated coffee, was assessed every four years by validated food-frequency questionnaires. Deaths from suicide were determined by physician review of death certificates. Multivariate adjusted relative risks (RRs) were estimated with Cox proportional hazard models. Cohort specific RRs were pooled using random-effect models. Results We documented 277 deaths from suicide. Compared to those consuming ≤1 cup/week of caffeinated coffee (≤8 oz/237 ml), the pooled multivariate RR (95% confidence interval [CI]) of suicide was 0.55 (0.38–0.78) for those consuming 2–3 cups/day and 0.47 (0.27–0.81) for those consuming ≥4 cups/day (P trend <0.001). The pooled multivariate RR (95% CI) for suicide was 0.75 (0.63–0.90) for each increment of 2 cups/day of caffeinated coffee and 0.77 (0.63–0.93) for each increment of 300 mg/day of caffeine. Conclusions These results from three large cohorts support an association between caffeine consumption and lower risk of suicide. PMID:23819683

Assessing the effect of quantitative and qualitative predictors on gastric cancer individuals survival using hierarchical artificial neural network models.

PubMed

Amiri, Zohreh; Mohammad, Kazem; Mahmoudi, Mahmood; Parsaeian, Mahbubeh; Zeraati, Hojjat

2013-01-01

There are numerous unanswered questions in the application of artificial neural network models for analysis of survival data. In most studies, independent variables have been studied as qualitative dichotomous variables, and results of using discrete and continuous quantitative, ordinal, or multinomial categorical predictive variables in these models are not well understood in comparison to conventional models. This study was designed and conducted to examine the application of these models in order to determine the survival of gastric cancer patients, in comparison to the Cox proportional hazards model. We studied the postoperative survival of 330 gastric cancer patients who suffered surgery at a surgical unit of the Iran Cancer Institute over a five-year period. Covariates of age, gender, history of substance abuse, cancer site, type of pathology, presence of metastasis, stage, and number of complementary treatments were entered in the models, and survival probabilities were calculated at 6, 12, 18, 24, 36, 48, and 60 months using the Cox proportional hazards and neural network models. We estimated coefficients of the Cox model and the weights in the neural network (with 3, 5, and 7 nodes in the hidden layer) in the training group, and used them to derive predictions in the study group. Predictions with these two methods were compared with those of the Kaplan-Meier product limit estimator as the gold standard. Comparisons were performed with the Friedman and Kruskal-Wallis tests. Survival probabilities at different times were determined using the Cox proportional hazards and a neural network with three nodes in the hidden layer; the ratios of standard errors with these two methods to the Kaplan-Meier method were 1.1593 and 1.0071, respectively, revealed a significant difference between Cox and Kaplan-Meier (P < 0.05) and no significant difference between Cox and the neural network, and the neural network and the standard (Kaplan-Meier), as well as better accuracy for the neural network (with 3 nodes in the hidden layer). Probabilities of survival were calculated using three neural network models with 3, 5, and 7 nodes in the hidden layer, and it has been observed that none of the predictions was significantly different from results with the Kaplan-Meier method and they appeared more comparable towards the last months (fifth year). However, we observed better accuracy using the neural network with 5 nodes in the hidden layer. Using the Cox proportional hazards and a neural network with 3 nodes in the hidden layer, we found enhanced accuracy with the neural network model. Neural networks can provide more accurate predictions for survival probabilities compared to the Cox proportional hazards mode, especially now that advances in computer sciences have eliminated limitations associated with complex computations. It is not recommended in order to adding too many hidden layer nodes because sample size related effects can reduce the accuracy. We recommend increasing the number of nodes to a point that increased accuracy continues (decrease in mean standard error), however increasing nodes should cease when a change in this trend is observed.

The Impact of the Crown-Root Ratio on Survival of Abutment Teeth for Dentures.

PubMed

Tada, S; Allen, P F; Ikebe, K; Zheng, H; Shintani, A; Maeda, Y

2015-09-01

Crown-root ratio (CRR) is commonly recorded when planning prosthodontic procedures. However, there is a lack of longitudinal clinical data evaluating the association between CRR and tooth survival. The aim of this longitudinal practice-based study was to assess the impact of CRR on the survival of abutment teeth for removable partial dentures (RPDs). Data were collected from 147 patients provided with RPDs at a dental hospital in Japan. In total, 236 clasp-retained RPDs and 856 abutment teeth were analyzed. Survival of abutment teeth was assessed using Kaplan-Meier methods and Cox's proportional hazard (PH) regression. The Cox PH regression was used to assess the prognostic significance of initial CRR value with adjustments for clinically relevant factors, including age, sex, frequency of periodontal maintenance programs, occlusal support area, type of abutment tooth, status of endodontic treatment, and probing pocket depth. Abutment teeth were divided into 1 of 5 risk groups according to CRR: A (≤0.75), B (0.76-1.00), C (1.01-1.25), D (1.26-1.50) and E (≥1.51). The 7-year survival rate was 89.1% for group A, 85.9% for group B, 86.5% for group C, 76.9% for group D, and 46.7% for group E. The survival curves of groups A, B, and C were illustrated to be quite similar and favorable. The multivariable analysis treating CRR as a continuous variable allowed estimation of the hazard ratio at any specific CRR value. When CRR = 0.80 was set as a reference, the estimated hazard ratio was 0.58 for CRR = 0.50 (95% confidence interval [CI], 0.36-0.91), 1.13 for CRR = 1.00 (95% CI, 0.93-1.37), 1.35 for CRR = 1.25 (95% CI, 1.02-1.80), 1.53 for CRR = 1.50 (95% CI, 1.15-2.08), or 1.95 for CRR = 2.00 (95% CI, 1.44-2.65). These practice-based longitudinal data provide information to improve the evidence-based prognosis of teeth in providing prosthodontic procedures. © International & American Associations for Dental Research.

Prognostic and survival analysis of 837 Chinese colorectal cancer patients.

PubMed

Yuan, Ying; Li, Mo-Dan; Hu, Han-Guang; Dong, Cai-Xia; Chen, Jia-Qi; Li, Xiao-Fen; Li, Jing-Jing; Shen, Hong

2013-05-07

To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P < 0.05. The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage III CRC (P < 0.0001). We divided 341 stage III patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage III CRC patients.

Impact of age, sex, therapeutic intent, race and severity of advanced heart failure on short-term principal outcomes in the MOMENTUM 3 trial.

PubMed

Goldstein, Daniel J; Mehra, Mandeep R; Naka, Yoshifumi; Salerno, Christopher; Uriel, Nir; Dean, David; Itoh, Akinobu; Pagani, Francis D; Skipper, Eric R; Bhat, Geetha; Raval, Nirav; Bruckner, Brian A; Estep, Jerry D; Cogswell, Rebecca; Milano, Carmelo; Fendelander, Lahn; O'Connell, John B; Cleveland, Joseph

2018-01-01

Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Cox proportional hazard models were used to analyze patients enrolled in the "as-treated cohort" (n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Baseline characteristics were well balanced among HM3 (n = 151) and HMII (n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Phobic anxiety symptom scores and incidence of type 2 diabetes in US men and women.

PubMed

Farvid, Maryam S; Qi, Lu; Hu, Frank B; Kawachi, Ichiro; Okereke, Olivia I; Kubzansky, Laura D; Willett, Walter C

2014-02-01

Emotional stress may be a risk factor for type 2 diabetes (T2D), but the relation between phobic anxiety symptoms and risk of T2D is uncertain. To evaluate prospectively the association between phobic anxiety symptoms and incident T2D in three cohorts of US men and women. We followed 30,791 men in the Health Professional's Follow-Up Study (HPFS) (1988-2008), 68,904 women in the Nurses' Health Study (NHS) (1988-2008), and 79,960 women in the Nurses' Health Study II (NHS II) (1993-2011). Phobic anxiety symptom scores, as measured by the Crown-Crisp index (CCI), calculated from 8 questions, were administered at baseline and updated in 2004 for NHS, in 2005 for NHS II, and in 2000 for HPFS. Incident T2D was confirmed by a validated supplementary questionnaire. We used Cox proportional hazards analysis to evaluate associations with incident T2D. During 3,099,651 person-years of follow-up, we documented 12,831 incident T2D cases. In multivariate Cox proportional-hazards models with adjustment for major lifestyle and dietary risk factors, the hazard ratios (HRs) of T2D across categories of increasing levels of CCI (scores=2 to <3, 3 to <4, 4 to <6, ⩾6), compared with a score of <2, were increased significantly by 6%, 10%, 10% and 13% (Ptrend=0.001) for NHS; and by 19%, 11%, 21%, and 29% (Ptrend<0.0001) for NHS II. Each score increment in CCI was associated with 2% higher risk of T2D in NHS (HRs, 1.02, 95% confidence intervals: 1.01-1.03) and 4% higher risk of T2D in NHS II (HRs, 1.04, 95% confidence intervals: 1.02-1.05). Further adjustment for depression did not change the results. In HPFS, the association between CCI and T2D was not significant after adjusting for lifestyle variables. Our results suggest that higher phobic anxiety symptoms are associated with an increased risk of T2D in women. Copyright © 2013 Elsevier Inc. All rights reserved.

Prognostic value of FDG PET/CT-based metabolic tumor volumes in metastatic triple negative breast cancer patients

PubMed Central

Marinelli, Brett; Espinet-Col, Carina; Ulaner, Gary A; McArthur, Heather L; Gonen, Mithat; Jochelson, Maxine; Weber, Wolfgang A

2016-01-01

FDG PET/CT-based measures of tumor burden show promise to predict survival in patients with metastatic breast cancer, but the patient populations studied so far are heterogeneous. The reports may have been confounded by the markedly different prognosis of the various subtypes of breast cancer. The purpose of this study is to evaluate the correlation between tumor burden on FDG PET/CT and overall survival (OS) in patients within a defined population: metastatic triple negative breast cancer (MTNBC). FDG PET/CT scans of 47 consecutive MTNBC patients (54±12 years-old) with no other known malignancies were analyzed. A total 393 lesions were identified, and maximum standardized uptake value (SUVmax), mean SUV, metabolic tumor volume (MTV), total lesion number (TLN) and total lesion glycolysis (TLG), were measured and correlated with patient survival by Mantel-Cox tests and Cox regression analysis. At a median follow-up time of 12.4 months, 41 patients died with a median OS of 12.1 months. Patients with MTV less than 51.5 ml lived nearly three times longer (22 vs 7.1 months) than those with a higher MTV (χ2=21.3, P<0.0001). In a multivariate Cox regression analysis only TLN and MTV were significantly correlated with survival. Those with an MTV burden in the 75th percentile versus the 25th percentile had a hazard ratio of 6.94 (p=0.001). In patients with MTNBC, MTV appears to be a strong prognostic factor. If validated in prospective studies, MTV may be a valuable tool for risk stratification of MTNBC patients in clinical trials and to guide patient management. PMID:27186439

Quantitative assessment of metal elements using moss species as biomonitors in downwind area of lead-zinc mine.

PubMed

Balabanova, Biljana; Stafilov, Trajče; Šajn, Robert; Andonovska, Katerina Bačeva

2017-02-23

Distributions of a total of 21 elements were monitored in significantly lead-zinc polluted area using moss species (Hypnum cupressiforme and Camptothecium lutescens) used interchangeably, covering a denser sampling network. Interspecies comparison was conducted using Box-Cox transformed values, due to their skewed distribution. The median concentrations of trace elements in the both mosses examined decreased in the following order: Fe>Mn>Zn>Pb>Cu>Ni∼Cr∼As>Co>Cd>Hg. For almost all analyzed elements, H. cupressiforme revealed higher bio-accumulative abilities. For arsenic contents was obtained ER-value in favor of C. lutescens. The ER for the element contents according to the distance from the pollution source in selected areas was significantly enriched for the anthropogenic introduced elements As, Cd, Cu, Pb and Zn. After Box-Cox transformation of the content values, T B was significantly different for As (4.82), Cd (3.84), Cu (2.95), Pb (4.38), and Zn (4.23). Multivariate factor analysis singled out four elemental associations: F1 (Al-Co-Cr-Fe-Li-Ni-V), F2 (Cd-Pb-Zn), F3 (Ca-Mg-Na-P) and F4 (Cu) with a total variance of 89%. Spatial distribution visualized the hazardously higher contents of "hot spots" of Cd > 1.30 mg/kg, Cu > 22 mg/kg, Pb > 130 mg/kg and Zn > 160 mg/kg. Therefore, main approach in moss biomonitoring should be based on data management of the element distribution by reducing the effect of extreme values (considering Box-Cox data transformation); the interspecies variation in sampling media does not deviate in relation to H. cupressiforme vs. C. lutescens.

NSAIDs and spontaneous abortions – true effect or an indication bias?

PubMed Central

Daniel, Sharon; Koren, Gideon; Lunenfeld, Eitan; Levy, Amalia

2015-01-01

Aim The aim of the study was to characterize the extent of indication bias resulting from the excessive use of NSAIDs on the days preceding a spontaneous abortion to relieve pain. Methods We used data from a retrospective cohort study assessing the risk for spontaneous abortions following exposure to NSAIDs. Three definitions of exposure for cases of spontaneous abortions were compared, from the first day of pregnancy until the day of spontaneous abortion and until 3 and 2 days before a spontaneous abortion. Statistical analysis was performed using multivariate time programmed Cox regression. Results A sharp increase was observed in the dispensation of indomethacin, diclofenac and naproxen, and a milder increase was found in the use of ibuprofen during the week before a spontaneous abortion. Non- selective COX inhibitors in general and specifically diclofenac and indomethacin were found to be associated with spontaneous abortions when the exposure period was defined until the day of spontaneous abortion (hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04, 1.28; HR 1.31, 95% CI 1.08, 1.59 and HR 3.33, 95% CI 2.09, 5.29, respectively). The effect disappears by excluding exposures occurring on the day before the spontaneous abortion for non-selective COX inhibitors and on the last week before the spontaneous abortion for indomethacin. In general, decreasing HRs were found with the exclusion of exposures occurring on the days immediately before the spontaneous abortion. Conclusions The increased use of NSAIDs during the last few days that preceded a spontaneous abortion to relieve pain associated with the miscarriage could bias studies assessing the association between exposure to NSAIDs and spontaneous abortions. PMID:25858169

Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

PubMed Central

Kempny, Aleksander; Diller, Gerhard-Paul; Alonso-Gonzalez, Rafael; Uebing, Anselm; Rafiq, Isma; Li, Wei; Swan, Lorna; Hooper, James; Donovan, Jackie; Wort, Stephen J; Gatzoulis, Michael A; Dimopoulos, Konstantinos

2015-01-01

Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population. PMID:25736048

The Cox proportional Hazard model on duration of birth process

NASA Astrophysics Data System (ADS)

Wuryandari, Triastuti; Haryatmi Kartiko, Sri; Danardono

2018-05-01

The duration of birth process, which is measured from the birth sign until baby born, is one important factor to the whole outcome of delivery process. There is a method of birth process that given relaxing and gentle treatment to the mother caled as gentlebirth. Gentlebirth is a method of birth process that combines brain science, birth science and technology to empower positive birth without pain. However the effect of method to the duration of birth process is still need empirical investigations. Therefore, the objective of this paper is to analyze the duration of birth process using the appropriate statistical methods for durational data, survival data or time to event data. Since there are many variables or factor that may affect the duration, a regression model is considerated. The flexibility of the Cox Proportional Hazard Model in the sense that there is no distributional assumption required, makes the Cox Model as the appropriate model and method to analyze the duration birth process. It is concluded that the Gentlebirth method affects on duration of birth process, with Hazard Ratio of 2.073, showing that the duration of birth process with gentlebirth method is faster than the other method.

Statistical power to detect violation of the proportional hazards assumption when using the Cox regression model.

PubMed

Austin, Peter C

2018-01-01

The use of the Cox proportional hazards regression model is widespread. A key assumption of the model is that of proportional hazards. Analysts frequently test the validity of this assumption using statistical significance testing. However, the statistical power of such assessments is frequently unknown. We used Monte Carlo simulations to estimate the statistical power of two different methods for detecting violations of this assumption. When the covariate was binary, we found that a model-based method had greater power than a method based on cumulative sums of martingale residuals. Furthermore, the parametric nature of the distribution of event times had an impact on power when the covariate was binary. Statistical power to detect a strong violation of the proportional hazards assumption was low to moderate even when the number of observed events was high. In many data sets, power to detect a violation of this assumption is likely to be low to modest.

Statistical power to detect violation of the proportional hazards assumption when using the Cox regression model

PubMed Central

Austin, Peter C.

2017-01-01

The use of the Cox proportional hazards regression model is widespread. A key assumption of the model is that of proportional hazards. Analysts frequently test the validity of this assumption using statistical significance testing. However, the statistical power of such assessments is frequently unknown. We used Monte Carlo simulations to estimate the statistical power of two different methods for detecting violations of this assumption. When the covariate was binary, we found that a model-based method had greater power than a method based on cumulative sums of martingale residuals. Furthermore, the parametric nature of the distribution of event times had an impact on power when the covariate was binary. Statistical power to detect a strong violation of the proportional hazards assumption was low to moderate even when the number of observed events was high. In many data sets, power to detect a violation of this assumption is likely to be low to modest. PMID:29321694

Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.

PubMed

Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C

2015-03-01

To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prospective Validation of a Screening Biomarker Approach Combining Amino-Terminal Pro-Brain Natriuretic Peptide With Galectin-3 Predicts Death and Cardiovascular Events in Asymptomatic Hemodialysis Patients.

PubMed

Voroneanu, Luminita; Siriopol, Dimitrie; Apetrii, Mugurel; Hogas, Simona; Onofriescu, Mihai; Nistor, Ionut; Kanbay, Mehmet; Dumea, Raluca; Cusai, Silvia; Cianga, Petru; Constantinescu, Daniela; Covic, Adrian

2018-05-01

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey

PubMed Central

Chen, Ying-Jen; Liang, Chang-Min; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lin, Tzu-Yu; Chung, Chi-Hsiang; Lin, Fu-Huang; Tsao, Chang-Huei; Chien, Wu-Chien

2017-01-01

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767–3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss. PMID:29156847

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey.

PubMed

Chen, Ying-Jen; Liang, Chang-Min; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lin, Tzu-Yu; Chung, Chi-Hsiang; Lin, Fu-Huang; Tsao, Chang-Huei; Chien, Wu-Chien

2017-10-17

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767-3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss.

Social consequences of multiple sclerosis: clinical and demographic predictors - a historical prospective cohort study.

PubMed

Pfleger, C C H; Flachs, E M; Koch-Henriksen, N

2010-11-01

Time to disability pension is one of the endpoints to be used to determine the prognosis of multiple sclerosis (MS) in prospective studies.   To assess the time to cessation of work and receiving disability pension in MS, and how it may depend on gender, type of work and age and symptom at onset. A total of 2240 Danes with onset of definite/probable MS 1980-1989, identified from the Danish MS-Registry, were included. Information on social endpoints was retrieved from Statistics Denmark. Cox regression analyses were used with onset as starting point. Afferent onset symptoms [hazard ratio (HR 0.57)] and non-physical type of work (HR 0.70) were favourable prognostic factors compared with high age at onset, physical work and efferent symptoms at onset. The mean time to disability pension was 13 years for patients with afferent/brainstem onset symptom but 8.7 years for those with efferent onset symptoms (P < 0.0001). The effect of onset symptom was reduced and the effect of sex became significant when all covariates and age at onset were included in multivariate Cox regression. Onset age, type of onset symptom and work are robust predictors of disability pension in MS. Disability pension proves to be a reliable milestone in estimation of the prognosis of MS. © 2010 The Author(s). Journal compilation © 2010 EFNS.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

[Psychiatric readmissions: individual and organizational factors].

PubMed

Plancke, Laurent; Amariei, Alina; Flament, Clara; Dumesnil, Chloé

2017-01-01

Psychiatric readmission often constitutes a criterion to assess the effects of various therapies, as well as the impact of organizational changes in the healthcare system. It is used to characterize relapse or decompensation. The purpose of this study was to determine readmission rates and identify individual and organizational factors associated with significant variations in these rates. Adult psychiatric readmissions were identified from the full-time hospital stays registered in psychiatric wards in 2011-2012 in the Nord and Pas-de-Calais departments of France, available in the medical the RimP psychiatric admission database. Readmission rates for various follow-up periods after discharge were measured by Kaplan-Meier survival analysis and multivariate analysis was conducted using the Cox proportional hazards model. Approximately 30,000 adults were hospitalized full-time in psychiatric units of the region during the study period. The 24-month readmission rate was 51.6% (95%CI: 50.8-52.3%). The Cox model showed that a diagnosis of schizophrenia (F2 - HR = 1.72 - 95%CI: 1.61-1.84 - p < 0.001) and personality disorder (F6 - HR = 1.45 - 95%CI: 1.32-1.58 - p < 0.001) was associated with a higher readmission rate. Readmission rates were higher among dependent patients in non-profit private hospitals. Psychiatric readmission is a very frequent event and is linked to organizational as well as individual factors.

A novel risk score for mortality in renal transplant recipients beyond the first posttransplant year.

PubMed

Hernández, Domingo; Sánchez-Fructuoso, Ana; González-Posada, José Manuel; Arias, Manuel; Campistol, Josep María; Rufino, Margarita; Morales, José María; Moreso, Francesc; Pérez, Germán; Torres, Armando; Serón, Daniel

2009-09-27

All-cause mortality is high after kidney transplantation (KT), but no prognostic index has focused on predicting mortality in KT using baseline and emergent comorbidity after KT. A total of 4928 KT recipients were used to derive a risk score predicting mortality. Patients were randomly assigned to two groups: a modeling population (n=2452), used to create a new index, and a testing population (n=2476), used to test this index. Multivariate Cox regression model coefficients of baseline (age, weight, time on dialysis, diabetes, hepatitis C, and delayed graft function) and emergent comorbidity within the first posttransplant year (diabetes, proteinuria, renal function, and immunosuppressants) were used to weigh each variable in the calculation of the score and allocated into risk quartiles. The probability of death at 3 years, estimated by baseline cumulative hazard function from the Cox model [P (death)=1-0.993592764 (exp(score/100)], increased from 0.9% in the lowest-risk quartile (score=40) to 4.7% in the highest risk-quartile (score=200). The observed incidence of death increased with increasing risk quartiles in testing population (log-rank analysis, P<0.0001). The overall C-index was 0.75 (95% confidence interval: 0.72-0.78) and 0.74 (95% confidence interval: 0.70-0.77) in both populations, respectively. This new index is an accurate tool to identify high-risk patients for mortality after KT.

Substantial adverse association of visual and vascular comorbidities on visual disability in multiple sclerosis.

PubMed

Marrie, Ruth Ann; Cutter, Gary; Tyry, Tuula

2011-12-01

Visual comorbidities are common in multiple sclerosis (MS) but the impact of visual comorbidities on visual disability is unknown. We assessed the impact of visual and vascular comorbidities on severity of visual disability in MS. In 2006, we queried participants of the North American Research Committee on Multiple Sclerosis (NARCOMS) about cataracts, glaucoma, uveitis, hypertension, hypercholesterolemia, heart disease, diabetes and peripheral vascular disease. We assessed visual disability using the Vision subscale of Performance Scales. Using Cox regression, we investigated whether visual or vascular comorbidities affected the time between MS symptom onset and the development of mild, moderate and severe visual disability. Of 8983 respondents, 1415 (15.9%) reported a visual comorbidity while 4745 (52.8%) reported a vascular comorbidity. The median (interquartile range) visual score was 1 (0-2). In a multivariable Cox model the risk of mild visual disability was higher among participants with vascular (hazard ratio [HR] 1.45; 95% confidence interval [CI]: 1.39-1.51) and visual comorbidities (HR 1.47; 95% CI: 1.37-1.59). Vascular and visual comorbidities were similarly associated with increased risks of moderate and severe visual disability. Visual and vascular comorbidities are associated with progression of visual disability in MS. Clinicians hearing reports of worsening visual symptoms in MS patients should consider visual comorbidities as contributing factors. Further study of these issues using objective, systematic neuro-ophthalmologic evaluations is warranted.

Success and duration of dynamic bracing for pectus carinatum: A four-year prospective study.

PubMed

Emil, Sherif; Sévigny, Marika; Montpetit, Kathleen; Baird, Robert; Laberge, Jean-Martin; Goyette, Jade; Finlay, Ian; Courchesne, Guylaine

2017-01-01

This study sought to establish factors that can prognosticate outcomes of bracing for pectus carinatum (PC). Prospective data were collected on all patients enrolled in a dynamic bracing protocol from July 2011 to July 2015. Pressure of correction (POC) was measured at initiation of treatment, and pressure of treatment (POT) was measured pre- and post-adjustment at every follow-up visit. Univariate and Cox regression analysis tested the following possible determinants of success and bracing duration: age, sex, symmetry, POC, and POT drop during the first two follow-up visits. Of 114 patients, 64 (56%) succeeded, 33 (29%) were still in active bracing, and 17 (15%) failed or were lost to follow-up. In successful patients, active and maintenance bracing was 5.66±3.81 and 8.80±3.94months, respectively. Asymmetry and older age were significantly associated with failure. Multivariable Cox proportional hazard analysis of time-to-maintenance showed that asymmetry (p=0.01) and smaller first drop in POT (p=0.02) were associated with longer time to reach maintenance. Pressure of correction does not predict failure of bracing, but older age, asymmetry, and smaller first drop in pressure of treatment are associated with failure and longer bracing duration. Prospective Study/Level of Evidence IV. Copyright © 2017 Elsevier Inc. All rights reserved.

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population.

PubMed

Tao, Li; Chu, Laura; Wang, Lisa I; Moy, Lisa; Brammer, Melissa; Song, Chunyan; Green, Marjorie; Kurian, Allison W; Gomez, Scarlett L; Clarke, Christina A

2016-09-01

To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression. We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality. Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2- breast cancer. De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

Prognostic determinants of community-acquired bloodstream infection in type 2 diabetic patients in ED.

PubMed

Yo, Chia-Hung; Lee, Meng-Tse Gabriel; Gi, Weng-Tein; Chang, Shy-Shin; Tsai, Kuang-Chau; Chen, Shyr-Chyr; Lee, Chien-Chang

2014-12-01

The objective of the study is to describe the epidemiology and outcome of community-acquired bloodstream infection (BSI) in type 2 diabetic patients in emergency department (ED). All patients admitted to the ED of the university hospital from June 2010 to June 2011 with a history of type 2 diabetes mellitus and microbiologically documented BSI were retrospectively enrolled. Demographic characteristics, Charlson comorbidity index, antibiotic therapy, clinical severity, microbiological etiology, and diabetes-related complications were recorded in a standardized form. The major outcome measure was 30-day survival. χ2 Or Student t test was used for univariate analysis, and Cox proportional hazards models were used for multivariate analysis. Among 250 enrolled emergency patients with BSI, the overall 30-day mortality rate was 15.5%. Twenty-seven patients (10.7%) developed diabetic ketoacidosis (DKA), and 22 patients (8.8%) developed hyperosmolar hyperglycemic state. On univariate analysis, DKA rather than hyperosmolar hyperglycemic state was associated with adverse outcome. Other risk factors include higher mean glycated hemoglobin level, presence of underlying malignancy, long-term use of steroids, lower respiratory tract infection, and higher Charlson scores. Multivariate analysis identified 3 independent risk factors for early mortality when severity, comorbidity, age, and sex were under control: DKA (hazard ratio, 3.89; 95% confidence interval, 1.6-8.9), inappropriate antibiotics (2.25, 1.05-4.82), and chronic use of steroid (3.89, 1.1-13.2). In type 2 diabetic patients with BSI, a substantial proportion of patients developed DKA. This condition was probably underrecognized by clinicians and constituted an independent risk factor for short-term mortality. Other identified risk factors are potentially correctable and may allow preventive efforts to individuals at greatest potential benefit. Copyright © 2014 Elsevier Inc. All rights reserved.

Primary fascial closure with mesh reinforcement is superior to bridged mesh repair for abdominal wall reconstruction.

PubMed

Booth, Justin H; Garvey, Patrick B; Baumann, Donald P; Selber, Jesse C; Nguyen, Alexander T; Clemens, Mark W; Liu, Jun; Butler, Charles E

2013-12-01

Many surgeons believe that primary fascial closure with mesh reinforcement should be the goal of abdominal wall reconstruction (AWR), yet others have reported acceptable outcomes when mesh is used to bridge the fascial edges. It has not been clearly shown how the outcomes for these techniques differ. We hypothesized that bridged repairs result in higher hernia recurrence rates than mesh-reinforced repairs that achieve fascial coaptation. We retrospectively reviewed prospectively collected data from consecutive patients with 1 year or more of follow-up, who underwent midline AWR between 2000 and 2011 at a single center. We compared surgical outcomes between patients with bridged and mesh-reinforced fascial repairs. The primary outcomes measure was hernia recurrence. Multivariate logistic regression analysis was used to identify factors predictive of or protective for complications. We included 222 patients (195 mesh-reinforced and 27 bridged repairs) with a mean follow-up of 31.1 ± 14.2 months. The bridged repairs were associated with a significantly higher risk of hernia recurrence (56% vs 8%; hazard ratio [HR] 9.5; p < 0.001) and a higher overall complication rate (74% vs 32%; odds ratio [OR] 3.9; p < 0.001). The interval to recurrence was more than 9 times shorter in the bridged group (HR 9.5; p < 0.001). Multivariate Cox proportional hazard regression analysis identified bridged repair and defect width > 15 cm to be independent predictors of hernia recurrence (HR 7.3; p < 0.001 and HR 2.5; p = 0.028, respectively). Mesh-reinforced AWRs with primary fascial coaptation resulted in fewer hernia recurrences and fewer overall complications than bridged repairs. Surgeons should make every effort to achieve primary fascial coaptation to reduce complications. Published by Elsevier Inc.

Fruit and vegetable consumption and mortality in Eastern Europe: Longitudinal results from the Health, Alcohol and Psychosocial Factors in Eastern Europe study.

PubMed

Stefler, Denes; Pikhart, Hynek; Kubinova, Ruzena; Pajak, Andrzej; Stepaniak, Urszula; Malyutina, Sofia; Simonova, Galina; Peasey, Anne; Marmot, Michael G; Bobak, Martin

2016-03-01

It is estimated that disease burden due to low fruit and vegetable consumption is higher in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) than any other parts of the world. However, no large scale studies have investigated the association between fruit and vegetable (F&V) intake and mortality in these regions yet. The Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) study is a prospective cohort study with participants recruited from the Czech Republic, Poland and Russia. Dietary data was collected using food frequency questionnaire. Mortality data was ascertained through linkage with death registers. Multivariable adjusted hazard ratios were calculated by Cox regression models. Among 19,333 disease-free participants at baseline, 1314 died over the mean follow-up of 7.1 years. After multivariable adjustment, we found statistically significant inverse association between cohort-specific quartiles of F&V intake and stroke mortality: the highest vs lowest quartile hazard ratio (HR) was 0.52 (95% confidence interval (CI): 0.28-0.98). For total mortality, significant interaction (p = 0.008) between F&V intake and smoking was found. The associations were statistically significant in smokers, with HR 0.70 (0.53-0.91, p for trend: 0.011) for total mortality, and 0.62 (0.40-0.97, p for trend: 0.037) for cardiovascular disease (CVD) mortality. The association was appeared to be mediated by blood pressure, and F&V intake explained a considerable proportion of the mortality differences between the Czech and Russian cohorts. Our results suggest that increasing F&V intake may reduce CVD mortality in CEE and FSU, particularly among smokers and hypertensive individuals. © The European Society of Cardiology 2015.

Subclinical Hypothyroidism and Risk for Incident Myocardial Infarction Among Postmenopausal Women

PubMed Central

LeGrys, Vicky A.; Funk, Michele Jonsson; Lorenz, Carol E.; Giri, Ayush; Jackson, Rebecca D.; Manson, JoAnn E.; Schectman, Robin; Edwards, Todd L.; Heiss, Gerardo

2013-01-01

Context: Subclinical hypothyroidism (SCH) has been associated with an increased risk for cardiovascular disease. However, few studies have specifically examined the association between SCH and myocardial infarction (MI), and the relationship is poorly understood. Objectives: The purpose of this study was to evaluate incident MI risk in relation to SCH and severities of SCH among postmenopausal women. Methods: We used a population-based nested case-cohort design within the Women's Health Initiative observational study to examine the association between SCH and incident first-time MI risk among postmenopausal women in the United States. SCH was assessed using blood specimens collected at baseline. Participants presenting with normal free T4 levels and with thyrotropin levels of greater than 4.68–6.99 mU/L or 7.00 mU/L or greater were defined as having mild SCH or moderate/severe SCH, respectively. MI cases were centrally adjudicated by trained Women's Health Initiative staff. The primary analysis included 736 incident MI cases and 2927 randomly selected subcohort members. Multivariable adjusted Cox-proportional hazard models were used to assess MI risk in relation to SCH. Results: Compared with euthyroid participants, the multivariable adjusted hazard ratio (HR) for participants with any SCH was 1.05 [95% confidence interval (CI) 0.77–1.44]. HRs for participants with mild SCH, moderate/severe SCH, and moderate/severe SCH and the presence of antithyroid peroxidase antibodies (TPOAb) were 0.99 (95% CI 0.67–1.46), 1.19 (95% CI 0.72–1.96), and 0.90 (95% CI 0.47–1.74), respectively. Conclusion: We did not find evidence to suggest that SCH is associated with increased MI risk among a population of predominantly older postmenopausal women with no prior history of MI. PMID:23539723

Different Risk Factors of Proximal Junctional Kyphosis and Proximal Junctional Failure Following Long Instrumented Fusion to the Sacrum for Adult Spinal Deformity: Survivorship Analysis of 160 Patients.

PubMed

Park, Se-Jun; Lee, Chong-Suh; Chung, Sung-Soo; Lee, Jun-Young; Kang, Sang-Soo; Park, Se-Hwan

2017-02-01

The failure modes, time to development, and clinical relevance are known to differ between proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). However, there are no reports that study the risk factors of PJK and PJF separately. The aim of this study was to investigate the risk factors for PJK and PJF separately. A retrospective study of 160 consecutive patients who underwent a long instrumented fusion to the sacrum for adult spinal deformity with a minimum follow-up of 2 years was conducted. A separate survivorship analysis of PJK and PJF was performed using the Cox proportional hazards model for the 3 categorical parameters of surgical, radiographic, and patient factors. PJK developed in 27 patients (16.9%) and PJF in 29 patients (18.1%). The median survival time was 17.0 months for PJK and 3.0 months for PJF. Multivariate analyses revealed that a high body mass index was an independent risk factor for PJK (hazard ratio [HR] = 1.179), whereas the significant risk factors for PJF were older age, the presence of osteoporosis, the uppermost instrumented vertebra level at T11-L1, and a greater preoperative sagittal vertical axis (HR = 1.082, 6.465, 5.236, and 1.017, respectively). A large correction of sagittal deformity was shown to be a risk factor for PJF on univariate analyses, but not on multivariate analyses. PJK developed at a median of 17 months and PJF at a median of 3 months. A high body mass index was an independent risk factor for PJK, whereas older age, osteoporosis, uppermost instrumented vertebra level at the thoracolumbar junction, and greater preoperative sagittal vertical axis were risk factors for PJF.

Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soto, Daniel E., E-mail: dsoto2@partners.org; Passarelli, Michael N.; Daignault, Stephanie

2012-03-01

Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjustedmore » Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.« less

Different pathological features and prognosis in gastric cancer patients coming from high-risk and low-risk areas of Italy.

PubMed

Marrelli, Daniele; Pedrazzani, Corrado; Corso, Giovanni; Neri, Alessandro; Di Martino, Marianna; Pinto, Enrico; Roviello, Franco

2009-07-01

To compare clinicopathological features and long-term outcome in gastric cancer patients coming from high-risk and low-risk areas of Italy. Better survival rates have been reported from countries with higher incidence of gastric cancer. Data regarding 829 patients coming from Tuscany (group A) and 143 patients coming from Southern Italy (group B) were analyzed. Mean follow-up time was 56 +/- 57 months; it was 85 +/- 63 months in surviving patients or not tumor-related deaths. Prognostic factors were investigated by multivariate analysis with Cox proportional hazard model after verifying the assumption of proportionality of the risk associated with covariates. Lauren diffuse-mixed histotype, younger age, extended lymphadenectomy, and advanced stages were more common in group B. Gastric cancer-related 10-year survival probability was 48% in group A versus 29% in group B (log-rank test: P < 0.001). By multivariate analysis, geographic area was confirmed as a significant prognostic factor (hazard ratio for group B vs. group A: 1.52, 95% confidence interval: 1.12-2.06, P = 0.006). The influence of this factor on long-term survival was independent from other clinical, surgical, and pathologic factors, and was notable in neoplasms involving the serosa (10-year survival probability: 15% in group A vs. 3% in group B, log-rank test: P = 0.005). Patients coming from low-risk area of Italy showed distinct pathologic features, more advanced stage, and worse prognosis when compared with patients coming from high-risk area. These findings may be indicative of different tumor biology, and may contribute to partly explain worldwide geographic variability in prognosis reported in different series.

Comparison of Adjuvant Radiation Therapy Alone and Chemotherapy Alone in Surgically Resected Low-Grade Gliomas: Survival Analyses of 2253 Cases from the National Cancer Data Base.

PubMed

Wu, Jing; Neale, Natalie; Huang, Yuqian; Bai, Harrison X; Li, Xuejun; Zhang, Zishu; Karakousis, Giorgos; Huang, Raymond; Zhang, Paul J; Tang, Lei; Xiao, Bo; Yang, Li

2018-04-01

It is becoming increasingly common to incorporate chemotherapy (CT) with radiotherapy (RT) in the treatment of low-grade gliomas (LGGs) after surgical resection. However, there is a lack of literature comparing survival of patients who underwent RT or CT alone. The U.S. National Cancer Data Base was used to identify patients with histologically confirmed, World Health Organization grade 2 gliomas who received either RT alone or CT alone after surgery from 2004 to 2013. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity-score-matched analysis. In total, 2253 patients with World Health Organization grade 2 gliomas were included, of whom 1466 (65.1%) received RT alone and 787 (34.9%) CT alone. The median OS was 98.9 months for the RT alone group and 125.8 months for the CT alone group. On multivariable analysis, CT alone was associated with a significant OS benefit compared with RT alone (hazard ratio [HR], 0.405; 95% confidence interval, 0.277-0.592; P < 0.001). On subgroup analyses, the survival advantage of CT alone over RT alone persisted across all age groups, and for the subtotal resection and biopsy groups, but not in the gross total resection group. In propensity-score-matched analysis, CT alone still showed significantly improved OS compared with RT alone (HR, 0.612; 95% confidence interval, 0.506-0.741; P < 0.001). Our results suggest that CT alone was independently associated with longer OS compared with RT alone in patients with LGGs who underwent surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Use of Tanning Beds and Incidence of Skin Cancer

PubMed Central

Zhang, Mingfeng; Qureshi, Abrar A.; Geller, Alan C.; Frazier, Lindsay; Hunter, David J.; Han, Jiali

2012-01-01

Purpose We sought to evaluate the risk effect of tanning bed use on skin cancers among teenage and young adults. We also expected to determine whether a dose-response relationship was evident. Patients and Methods We observed 73,494 female nurses for 20 years (from 1989 to 2009) in a large and well-characterized cohort in the United States and investigated whether frequency of tanning bed use during high school/college and at ages 25 to 35 years were associated with a risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We used Cox proportional hazards models and carefully adjusted for host risk factors, ultraviolet index of residence, and sun exposure behaviors at a young age. Results During follow-up, 5,506 nurses were diagnosed with BCC, 403 with SCC, and 349 with melanoma. The multivariable-adjusted hazard ratio (HR) of skin cancer for an incremental increase in use of tanning beds of four times per year during both periods was 1.15 (95% CI, 1.11 to 1.19; P < .001) for BCC, 1.15 (95% CI, 1.01 to 1.31; P = .03) for SCC, and 1.11 (95% CI, 0.97 to 1.27; P = .13) for melanoma. Compared with tanning bed use at ages 25 to 35 years, we found a significantly higher risk of BCC for use during high school/college (multivariable-adjusted HR for use more than six times per year compared with no use was 1.73 during high school/college v 1.28 at ages 25 to 35 years; P for heterogeneity < .001). Conclusion Our data provide evidence for a dose-response relationship between tanning bed use and the risk of skin cancers, especially BCC, and the association is stronger for patients with a younger age at exposure. PMID:22370316

Use of tanning beds and incidence of skin cancer.

PubMed

Zhang, Mingfeng; Qureshi, Abrar A; Geller, Alan C; Frazier, Lindsay; Hunter, David J; Han, Jiali

2012-05-10

We sought to evaluate the risk effect of tanning bed use on skin cancers among teenage and young adults. We also expected to determine whether a dose-response relationship was evident. We observed 73,494 female nurses for 20 years (from 1989 to 2009) in a large and well-characterized cohort in the United States and investigated whether frequency of tanning bed use during high school/college and at ages 25 to 35 years were associated with a risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We used Cox proportional hazards models and carefully adjusted for host risk factors, ultraviolet index of residence, and sun exposure behaviors at a young age. During follow-up, 5,506 nurses were diagnosed with BCC, 403 with SCC, and 349 with melanoma. The multivariable-adjusted hazard ratio (HR) of skin cancer for an incremental increase in use of tanning beds of four times per year during both periods was 1.15 (95% CI, 1.11 to 1.19; P < .001) for BCC, 1.15 (95% CI, 1.01 to 1.31; P = .03) for SCC, and 1.11 (95% CI, 0.97 to 1.27; P = .13) for melanoma. Compared with tanning bed use at ages 25 to 35 years, we found a significantly higher risk of BCC for use during high school/college (multivariable-adjusted HR for use more than six times per year compared with no use was 1.73 during high school/college v 1.28 at ages 25 to 35 years; P for heterogeneity < .001). Our data provide evidence for a dose-response relationship between tanning bed use and the risk of skin cancers, especially BCC, and the association is stronger for patients with a younger age at exposure.

Impact of treatment and insurance on socioeconomic disparities in survival after adolescent and young adult Hodgkin lymphoma: A population-based study

PubMed Central

Keegan, Theresa H.M.; DeRouen, Mindy C.; Parsons, Helen M.; Clarke, Christina A.; Goldberg, Debbie; Flowers, Christopher R.; Glaser, Sally L.

2015-01-01

Background Previous studies documented racial/ethnic and socioeconomic disparities in survival after Hodgkin lymphoma (HL) among adolescents and young adults (AYAs), but did not consider the influence of combined-modality treatment and health insurance. Methods Data for 9,353 AYA patients aged 15–39 when diagnosed with HL during 1988–2011 were obtained from the California Cancer Registry. Using multivariate Cox proportional hazards regression, we examined the impact of socio-demographic characteristics (race/ethnicity, neighborhood socioeconomic status (SES), and health insurance), initial combined-modality treatment, and subsequent cancers on survival. Results Over the 24-year study period, we observed improvements in HL-specific survival by diagnostic period and differences in survival by race/ethnicity, neighborhood SES and health insurance for a subset of more recently diagnosed patients (2001–2011). In multivariable analyses, HL-specific survival was worse for Blacks than Whites with early-stage (Hazard Ratio (HR): 1.68; 95% Confidence Interval (CI): 1.14, 2.49) and late-stage disease (HR: 1.68; 95% CI: 1.17, 2.41) and for Hispanics than Whites with late-stage disease (HR: 1.58; 95% CI: 1.22, 2.04). AYAs diagnosed with early-stage disease experienced worse survival if they also resided in lower SES neighborhoods (HR: 2.06; 95% CI: 1.59, 2.68). Furthermore, more recently diagnosed AYAs with public health insurance or who were uninsured experienced worse HL-specific survival (HR: 2.08; 95% CI: 1.52, 2.84). Conclusion Our findings identify several subgroups of HL patients at higher risk for HL mortality. Impact Identifying and reducing barriers to recommended treatment and surveillance in these AYAs at much higher risk of mortality is essential to ameliorating these survival disparities. PMID:26826029

Cardiovascular disease incidence in adolescent and young adult cancer survivors: a retrospective cohort study.

PubMed

Keegan, Theresa H M; Kushi, Lawrence H; Li, Qian; Brunson, Ann; Chawla, X; Chew, Helen K; Malogolowkin, Marcio; Wun, Ted

2018-06-01

Few population-based studies have focused on cardiovascular disease (CVD) risk in adolescent and young adult (AYA; 15-39 years) cancer survivors and none have considered whether CVD risk differs by sociodemographic factors. Analyses focused on 79,176 AYA patients diagnosed with 14 first primary cancers in 1996-2012 and surviving > 2 years after diagnosis with follow-up through 2014. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. The cumulative incidence of developing CVD accounted for the competing risk of death. Multivariable Cox proportional hazards regression evaluated factors associated with CVD and the impact of CVD on mortality. Overall, 2249 (2.8%) patients developed CVD. Survivors of central nervous system cancer (7.3%), acute lymphoid leukemia (6.9%), acute myeloid leukemia (6.8%), and non-Hodgkin lymphoma (4.1%) had the highest 10-year CVD incidence. In multivariable models, African-Americans (hazard ratio (HR) = 1.55, 95% confidence interval (CI) = 1.33-1.81; versus non-Hispanic Whites), those with public/no health insurance (HR = 1.78, 95% CI = 1.61-1.96; versus private) and those who resided in lower socioeconomic status neighborhoods had a higher CVD risk. These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by eightfold or higher among AYAs who developed CVD. While cancer therapies are known to increase the risk of CVD, this study additionally shows that CVD risk varies by sociodemographic factors. The identification and mitigation of CVD risk factors in these subgroups may improve long-term patient outcomes.

Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in the Japanese Normotensive General Population.

PubMed

Takase, Hiroyuki; Sugiura, Tomonori; Kimura, Genjiro; Ohte, Nobuyuki; Dohi, Yasuaki

2015-07-29

Although there is a close relationship between dietary sodium and hypertension, the concept that persons with relatively high dietary sodium are at increased risk of developing hypertension compared with those with relatively low dietary sodium has not been studied intensively in a cohort. We conducted an observational study to investigate whether dietary sodium intake predicts future blood pressure and the onset of hypertension in the general population. Individual sodium intake was estimated by calculating 24-hour urinary sodium excretion from spot urine in 4523 normotensive participants who visited our hospital for a health checkup. After a baseline examination, they were followed for a median of 1143 days, with the end point being development of hypertension. During the follow-up period, hypertension developed in 1027 participants (22.7%). The risk of developing hypertension was higher in those with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to 1.50). In multivariate Cox proportional hazards regression analysis, baseline sodium intake and the yearly change in sodium intake during the follow-up period (as continuous variables) correlated with the incidence of hypertension. Furthermore, both the yearly increase in sodium intake and baseline sodium intake showed significant correlations with the yearly increase in systolic blood pressure in multivariate regression analysis after adjustment for possible risk factors. Both relatively high levels of dietary sodium intake and gradual increases in dietary sodium are associated with future increases in blood pressure and the incidence of hypertension in the Japanese general population. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Periodontal disease, tooth loss, and colorectal cancer risk: results from the Nurses’ Health Study

PubMed Central

Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S.; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A.; Ogino, Shuji; Chan, Andrew T.; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S.; Stampfer, Meir J.; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

2016-01-01

Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation, and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses’ Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25–32 teeth, the multivariable HR (95% CI) for CRC for women with < 17 teeth was 1.20 (1.04–1.39). With regard to tumor site, the HRs (95% CIs) for the same comparison were 1.23 (1.01–1.51) for proximal colon cancer, 1.03 (0.76–1.38) for distal colon cancer, and 1.48 (1.07–2.05) for rectal cancer. Additionally, compared to those without periodontal disease, HRs for CRC were 0.91 (95% CI 0.74–1.12) for periodontal disease, and 1.22 (95% CI 0.91–1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index, or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. PMID:27778343

Glycemic index, glycemic load and invasive breast cancer incidence in postmenopausal women: The PREDIMED study.

PubMed

Castro-Quezada, Itandehui; Sánchez-Villegas, Almudena; Martínez-González, Miguel Á; Salas-Salvadó, Jordi; Corella, Dolores; Estruch, Ramón; Schröder, Helmut; Álvarez-Pérez, Jacqueline; Ruiz-López, María D; Artacho, Reyes; Ros, Emilio; Bulló, Mónica; Sorli, Jose V; Fitó, Montserrat; Ruiz-Gutiérrez, Valentina; Toledo, Estefanía; Buil-Cosiales, Pilar; García Rodríguez, Antonio; Lapetra, José; Pintó, Xavier; Salaverría, Itziar; Tur, Josep A; Romaguera, Dora; Tresserra-Rimbau, Anna; Serra-Majem, Lluís

2016-11-01

The objective of this study was to evaluate the prospective associations between dietary glycemic index (GI) and glycemic load (GL) and the risk for invasive breast cancer incidence in postmenopausal women at high cardiovascular disease (CVD) risk. This study was conducted within the framework of the PREvención con DIeta MEDiterránea (PREDIMED) study, a nutritional intervention trial for primary cardiovascular prevention. We included 4010 women aged between 60 and 80 years who were initially free from breast cancer but at high risk for CVD disease. Dietary information was collected using a validated 137-item food frequency questionnaire. We assigned GI values using the International Tables of GI and GL values. Cases were ascertained through yearly consultation of medical records and through consultation of the National Death Index. Only cases confirmed by results from cytology tests or histological evaluation were included. We estimated multivariable-adjusted hazard ratios for invasive breast cancer risk across tertiles of energy-adjusted dietary GI/GL using Cox regression models. We repeated our analyses using yearly repeated measures of GI/GL intakes. No associations were found between baseline dietary GI/GL and invasive breast cancer incidence. The multivariable hazard ratio and 95% confidence interval (CI) for the top tertile of dietary GI was 1.02 (95% CI: 0.42-2.46) and for dietary GL was 1.00 (95% CI: 0.44-2.30) when compared with the bottom tertile. Repeated-measures analyses yielded similar results. In sensitivity analyses, no significant associations were observed for women with obesity or diabetes. Dietary GI and GL did not appear to be associated with an increased risk for invasive breast cancer in postmenopausal women at high CVD risk.

Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial.

PubMed

Bartlett, John M S; Christiansen, Jason; Gustavson, Mark; Rimm, David L; Piper, Tammy; van de Velde, Cornelis J H; Hasenburg, Annette; Kieback, Dirk G; Putter, Hein; Markopoulos, Christos J; Dirix, Luc Y; Seynaeve, Caroline; Rea, Daniel W

2016-01-01

Hormone receptors HER2/neu and Ki-67 are markers of residual risk in early breast cancer. An algorithm (IHC4) combining these markers may provide additional information on residual risk of recurrence in patients treated with hormone therapy. To independently validate the IHC4 algorithm in the multinational Tamoxifen Versus Exemestane Adjuvant Multicenter Trial (TEAM) cohort, originally developed on the trans-ATAC (Arimidex, Tamoxifen, Alone or in Combination Trial) cohort, by comparing 2 methodologies. The IHC4 biomarker expression was quantified on TEAM cohort samples (n = 2919) by using 2 independent methodologies (conventional 3,3'-diaminobezidine [DAB] immunohistochemistry with image analysis and standardized quantitative immunofluorescence [QIF] by AQUA technology). The IHC4 scores were calculated by using the same previously established coefficients and then compared with recurrence-free and distant recurrence-free survival, using multivariate Cox proportional hazards modeling. The QIF model was highly significant for prediction of residual risk (P < .001), with continuous model scores showing a hazard ratio (HR) of 1.012 (95% confidence interval [95% CI]: 1.010-1.014), which was significantly higher than that for the DAB model (HR: 1.008, 95% CI: 1.006-1.009); P < .001). Each model added significant prognostic value in addition to recognized clinical prognostic factors, including nodal status, in multivariate analyses. Quantitative immunofluorescence, however, showed more accuracy with respect to overall residual risk assessment than the DAB model. The use of the IHC4 algorithm was validated on the TEAM trial for predicting residual risk in patients with breast cancer. These data support the use of the IHC4 algorithm clinically, but quantitative and standardized approaches need to be used.

Suture, synthetic, or biologic in contaminated ventral hernia repair.

PubMed

Bondre, Ioana L; Holihan, Julie L; Askenasy, Erik P; Greenberg, Jacob A; Keith, Jerrod N; Martindale, Robert G; Roth, J Scott; Liang, Mike K

2016-02-01

Data are lacking to support the choice between suture, synthetic mesh, or biologic matrix in contaminated ventral hernia repair (VHR). We hypothesize that in contaminated VHR, suture repair is associated with the lowest rate of surgical site infection (SSI). A multicenter database of all open VHR performed at from 2010-2011 was reviewed. All patients with follow-up of 1 mo and longer were included. The primary outcome was SSI as defined by the Centers for Disease Control and Prevention. The secondary outcome was hernia recurrence (assessed clinically or radiographically). Multivariate analysis (stepwise regression for SSI and Cox proportional hazard model for recurrence) was performed. A total of 761 VHR were reviewed for a median (range) follow-up of 15 (1-50) mo: there were 291(38%) suture, 303 (40%) low-density and/or mid-density synthetic mesh, and 167(22%) biologic matrix repair. On univariate analysis, there were differences in the three groups including ethnicity, ASA, body mass index, institution, diabetes, primary versus incisional hernia, wound class, hernia size, prior VHR, fascial release, skin flaps, and acute repair. The unadjusted outcomes for SSI (15.1%; 17.8%; 21.0%; P = 0.280) and recurrence (17.8%; 13.5%; 21.5%; P = 0.074) were not statistically different between groups. On multivariate analysis, biologic matrix was associated with a nonsignificant reduction in both SSI and recurrences, whereas synthetic mesh associated with fewer recurrences compared to suture (hazard ratio = 0.60; P = 0.015) and nonsignificant increase in SSI. Interval estimates favored biologic matrix repair in contaminated VHR; however, these results were not statistically significant. In the absence of higher level evidence, surgeons should carefully balance risk, cost, and benefits in managing contaminated ventral hernia repair. Copyright © 2016 Elsevier Inc. All rights reserved.

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation.

PubMed

Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan; Xu, Jie

2017-01-01

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668-4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78-28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells.

PD-L2 expression in colorectal cancer: Independent prognostic effect and targetability by deglycosylation

PubMed Central

Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan

2017-01-01

ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668–4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78–28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells. PMID:28811964

Characteristics and risk of syphilis diagnosis among HIV-infected male cohort: a population-based study in Houston, Texas.

PubMed

Yang, Biru; Hallmark, Camden J; Huang, Jamie S; Wolverton, Marcia L; McNeese-Ward, Marlene; Arafat, Raouf R

2013-12-01

This population-based study assessed the characteristics, timing, and risk of syphilis diagnoses among HIV-infected males in Houston, Texas. A retrospective cohort of males newly diagnosed as having HIV between January 2000 and December 2002 was constructed using HIV surveillance data. These individuals were cross-referenced to sexually transmitted disease surveillance data to ascertain early syphilis diagnoses for the subsequent 10 years. Multivariable Cox regression was used to identify risk factors for syphilis diagnosis while controlling for the effects of covariates. Approximately 6% of the HIV-infected male cohort received early syphilis diagnoses during a 10-year period. Of these comorbid individuals, 40.8% received an incident syphilis diagnosis 5 years or more after their HIV diagnosis. Men who have sex with men (MSM) transmission risk was associated with significantly increased hazard of having a syphilis diagnosis in multivariable analysis (adjusted hazard ratio [HR] of a syphilis diagnosis, 5.24; 95% confidence interval, 3.41-8.05). Compared with men who were older than 40 years at HIV diagnosis, those 13 to 19 years old were 4.06 (2.18-7.55) times more likely to obtain a syphilis diagnosis. The HRs of having an HIV-syphilis comorbidity decreased as age increased. Compared with whites, non-Hispanic African Americans had 1.59 (1.11-2.26) times increased risk of having a subsequent syphilis diagnosis. Risk-stratified HRs showed that MSM had an increased risk of contracting syphilis in all race/ethnicity and age groups. This study suggests that HIV-positive African Americans, youth, and MSM had increased risk of having a subsequent syphilis diagnosis. Targeting these groups with STI prevention messaging may be beneficial to reducing comorbidity.

Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma.

PubMed

Haddad, Ahmed Q; Jiang, Lai; Cadeddu, Jeffrey A; Lotan, Yair; Gahan, Jeffrey C; Hynan, Linda S; Gupta, Neil; Raj, Ganesh V; Sagalowsky, Arthur I; Margulis, Vitaly

2015-12-01

To evaluate the association of statin use and preoperative serum lipid parameters with oncologic outcomes following surgery for renal cell carcinoma. A total of 850 patients who underwent surgery for localized renal cell carcinoma at our institution from 2000 to 2012 were included. Use of statins, preoperative serum lipid profile, and comprehensive clinicopathologic features were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox proportional hazards model were employed to compare survival outcomes. There were 342 statin users and 508 non-users. Median follow-up was 25.0 months. Statin users were older, had greater body mass index, and had worse performance status than non-users. Tumor pathologic characteristics were balanced between groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared with 87.6% for statin users (P = .004). After adjustment for clinicopathologic variables, statin use was independently associated with improved RFS (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides <250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P <.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis. Statin use was independently associated with improved survival, whereas elevated serum triglyceride levels correlated with worse oncologic outcomes in this cohort. These findings warrant validation in prospective studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Interleukin-6 predicts recurrence and survival among head and neck cancer patients.

PubMed

Duffy, Sonia A; Taylor, Jeremy M G; Terrell, Jeffrey E; Islam, Mozaffarul; Li, Yun; Fowler, Karen E; Wolf, Gregory T; Teknos, Theodoros N

2008-08-15

Increased pretreatment serum interleukin (IL)-6 levels among patients with head and neck squamous cell carcinoma (HNSCC) have been shown to correlate with poor prognosis, but sample sizes in prior studies have been small and thus unable to control for other known prognostic variables. A longitudinal, prospective cohort study determined the correlation between pretreatment serum IL-6 levels, and tumor recurrence and all-cause survival in a large population (N = 444) of previously untreated HNSCC patients. Control variables included age, sex, smoking, cancer site and stage, and comorbidities. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to study the association between IL-6 levels, control variables, and time to recurrence and survival. The median serum IL-6 level was 13 pg/mL (range, 0-453). The 2-year recurrence rate was 35.2% (standard error, 2.67%). The 2-year death rate was 26.5% (standard error, 2.26%). Multivariate analyses showed that serum IL-6 levels independently predicted recurrence at significant levels [hazard ratio (HR) = 1.32; 95% confidence interval (CI), 1.11 to 1.58; P = .002] as did cancer site (oral/sinus). Serum IL-6 level was also a significant independent predictor of poor survival (HR = 1.22; 95% CI, 1.02 to 1.46; P = .03), as were older age, smoking, cancer site (oral/sinus), higher cancer stage, and comorbidities. Pretreatment serum IL-6 could be a valuable biomarker for predicting recurrence and overall survival among HNSCC patients. Using IL-6 as a biomarker for recurrence and survival may allow for earlier identification and treatment of disease relapse. 2008 American Cancer Society

Clinical impact of prolonged diagnosis to treatment interval (DTI) among patients with oropharyngeal squamous cell carcinoma.

PubMed

Sharma, Sonam; Bekelman, Justin; Lin, Alexander; Lukens, J Nicholas; Roman, Benjamin R; Mitra, Nandita; Swisher-McClure, Samuel

2016-05-01

We examined practice patterns using the National Cancer Data Base (NCDB) to determine risk factors for prolonged diagnosis to treatment interval (DTI) and survival outcomes in patients receiving chemoradiation for oropharyngeal squamous cell carcinoma (OPSCC). We identified 6606 NCDB patients with Stage III-IV OPSCC receiving chemoradiation from 2003 to 2006. We determined risk factors for prolonged DTI (>30days) using univariate and multivariable logistic regression models. We examined overall survival (OS) using Kaplan Meier and multivariable Cox proportional hazards models. 3586 (54.3%) patients had prolonged DTI. Race, IMRT, insurance status, and high volume facilities were significant risk factors for prolonged DTI. Patients with prolonged DTI had inferior OS compared to DTI⩽30days (Hazard Ratio (HR)=1.12, 95% CI 1.04-1.20, p=0.005). For every week increase in DTI there was a 2.2% (95% CI 1.1-3.3%, p<0.001) increase in risk of death. Patients receiving IMRT, treatment at academic, or high-volume facilities were more likely to experience prolonged DTI (High vs. Low volume: 61.5% vs. 51.8%, adjusted OR 1.38, 95% CI 1.21-1.58; Academic vs. Community: 59.5% vs. 50.6%, adjusted OR 1.26, 95% CI 1.13-1.42; non-IMRT vs. IMRT: 53.4% vs. 56.5%; adjusted OR 1.17, 95% CI 1.04-1.31). Our results suggest that prolonged DTI has a significant impact on survival outcomes. We observed disparities in DTI by socioeconomic factors. However, facility level factors such as academic affiliation, high volume, and IMRT also increased risk of DTI. These findings should be considered in developing efficient pathways to mitigate adverse effects of prolonged DTI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sociodemographic disparities in the occurrence of medical conditions among adolescent and young adult Hodgkin lymphoma survivors.

PubMed

Keegan, Theresa H M; Li, Qian; Steele, Amy; Alvarez, Elysia M; Brunson, Ann; Flowers, Christopher R; Glaser, Sally L; Wun, Ted

2018-06-01

Hodgkin lymphoma (HL) survivors experience high risks of second cancers and cardiovascular disease, but no studies have considered whether the occurrence of these and other medical conditions differ by sociodemographic factors in adolescent and young adult (AYA) survivors. Data for 5,085 patients aged 15-39 when diagnosed with HL during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to hospitalization data. We examined the impact of race/ethnicity, neighborhood socioeconomic status (SES), and health insurance on the occurrence of medical conditions (≥ 2 years after diagnosis) and the impact of medical conditions on survival using multivariable Cox proportional hazards regression. Twenty-six percent of AYAs experienced at least one medical condition and 15% had ≥ 2 medical conditions after treatment for HL. In multivariable analyses, Black HL survivors had a higher likelihood (vs. non-Hispanic Whites) of endocrine [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.05-1.78] and circulatory system diseases (HR = 1.58, CI 1.17-2.14); Hispanics had a higher likelihood of endocrine diseases [HR = 1.24 (1.04-1.48)]. AYAs with public or no insurance (vs. private/military) had higher likelihood of circulatory system diseases, respiratory system diseases, chronic kidney disease/renal failure, liver disease, and endocrine diseases. AYAs residing in low SES neighborhoods (vs. high) had higher likelihood of respiratory system and endocrine diseases. AYAs with these medical conditions or second cancers had an over twofold increased risk of death. Strategies to improve health care utilization for surveillance and secondary prevention among AYA HL survivors at increased risk of medical conditions may improve outcomes.

Differential Impact of Net Atrioventricular Compliance on Clinical Outcomes in Patients with Mitral Stenosis According to Cardiac Rhythm.

PubMed

Cho, In-Jeong; Chang, Hyuk-Jae; Lee, Soo Yeon; Shim, Chi Young; Hong, Geu-Ru; Chung, Namsik

2017-06-01

Net atrioventricular compliance (Cn), a parameter for the net compliance of the left atrium and left ventricle, is known to be a useful predictor of outcomes in patients with mitral stenosis (MS). The present study aimed to evaluate whether the impact of Cn on symptom status and clinical outcomes, as well as its contribution toward systolic pulmonary artery pressure (SPAP), differed according to cardiac rhythm. We retrospectively reviewed patients (N = 308) with rheumatic pure MS. Doppler-derived Cn was calculated using planimetered mitral valve area and E-wave downslope of transmitral flow. The primary endpoint was defined as a composite of all-cause death, percutaneous mitral valvotomy, surgical mitral valve replacement, admission for heart failure, and stroke. Overall, there were 178 patients (58%) with sinus rhythm (SR) and 130 patients (42%) with atrial fibrillation (AF). In multivariable linear regression analysis, there was a significant independent association between Cn and SPAP in patients with SR (P = .014), but not in those with AF (P = .112). During a median follow-up of 38 months, 130 patients (27%) experienced the study endpoint. In multivariable Cox regression, high Cn was associated with a more favorable prognosis in patients with SR (hazard ratio = 0.83; 95% CI, 0.69-0.99; P = .038). Conversely, high Cn was not found to offset the burden of adverse clinical outcomes in those with AF (hazard ratio = 1.18; 95% CI, 0.99-1.40; P = .071). Cn appears to be associated with SPAP and clinical outcomes in MS patients with SR. The predictive role of Cn in patients with AF requires further clarification. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Association Between Severe Hypoglycemia and Cardiovascular Disease Risk in Japanese Patients With Type 2 Diabetes.

PubMed

Goto, Atsushi; Goto, Maki; Terauchi, Yasuo; Yamaguchi, Naohito; Noda, Mitsuhiko

2016-03-09

It remains unclear whether severe hypoglycemia is associated with cardiovascular disease (CVD) in Asian populations with type 2 diabetes (T2D). Furthermore, no study in Japan, where the prescription patterns differ from those in other countries, has examined this association. We retrospectively included 58 223 patients (18-74 years old) with T2D. First, we examined the potential predictors of severe hypoglycemia. Then, we investigated the association between severe hypoglycemia and CVD risk. Finally, we performed an updated systematic review and meta-analysis to incorporate our findings and recently published studies into the previous systematic review and meta-analysis. During 134 597 person-years from cumulative observation periods, 128 persons experienced severe hypoglycemia and 550 developed CVD events. In a multivariate Cox proportional hazard model, severe hypoglycemia was strongly and positively associated with the risk of CVD (multivariate-adjusted adjusted hazard ratio, 3.39; 95% CI, 1.25-9.18). In a propensity score-matched cohort that had similar baseline characteristics for patients with severe hypoglycemia and those without, severe hypoglycemia was more strongly associated with the risk of CVD. An updated systematic review and meta-analysis that included 10 studies found that severe hypoglycemia was associated with an ≈2-fold increased risk of CVD (pooled relative risk, 1.91; 95% CI, 1.69-2.15). Our results suggest that severe hypoglycemia is strongly associated with an increased risk of CVD in Japanese patients with T2D, further supporting the notion that avoiding severe hypoglycemia may be important in preventing CVD in this patient population. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Gender Differences in Receipt of National Institutes of Health R01 Grants Among Junior Faculty at an Academic Medical Center: The Role of Connectivity, Rank, and Research Productivity.

PubMed

Warner, Erica T; Carapinha, René; Weber, Griffin M; Hill, Emorcia V; Reede, Joan Y

2017-10-01

To determine whether there were gender differences in likelihood of receiving a first National Institutes of Health (NIH) R01 award among 5445 instructors and assistant professors at Harvard Medical School (HMS). Data on R01 award principal investigators were obtained from NIH ExPORTER and linked with faculty data. Using Cox proportional hazard regression, we examined the association of gender with receipt of first R01 award between 2008 and 2015 accounting for demographics, research productivity metrics, and professional characteristics. Compared to males, females had fewer publications, lower h-index, smaller coauthor networks and were less likely to be assistant professors (p < 0.0001). Four hundred and thirteen of 5445 faculty (7.6%) received their first R01 award during the study period. There was no gender difference in receipt of R01 awards in age-adjusted (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.70-1.08) or multivariable-adjusted models (HR: 1.07, 95% CI: 0.86-1.34). Compared to white males, there was a nonsignificant 10%, 18%, and 30% lower rate of R01 receipt among white, Asian or Pacific Islander, and underrepresented minority females, respectively. These differences were eliminated in the multivariable-adjusted model. Network reach, age, HMS start year, h-index, academic rank, previous K award, terminal degree, and HMS training were all significant predictors of receiving an R01 award. A relatively small proportion of HMS junior faculty obtained their first NIH R01 award during the study period. There was no significant gender difference in likelihood of award. However, we are unable to distinguish faculty that never applied from those who applied and were not successful.

Comparison of rehospitalization rates and associated costs among patients with schizophrenia receiving paliperidone palmitate or oral antipsychotics.

PubMed

Lafeuille, Marie-Hélène; Grittner, Amanda Melina; Fortier, Jonathan; Muser, Erik; Fasteneau, John; Duh, Mei Sheng; Lefebvre, Patrick

2015-03-01

Comparative data on rehospitalization patterns and associated institutional costs after inpatient treatment with paliperidone palmitate or oral antipsychotic therapy are reported. A retrospective cohort study was conducted using discharge and billing records from a large hospital database. Selected clinical and cost outcomes were compared in a cohort of adult patients who received the long-acting antipsychotic paliperidone palmitate during a schizophrenia-related index hospital stay and a cohort of patients who received oral antipsychotic therapy during their index admission. Inverse probability-of-treatment weights based on propensity scores were used to reduce confounding. Rates of all-cause and schizophrenia-related rehospitalization and emergency room (ER) use in the two cohorts over periods of up to 12 months were analyzed using a multivariate Cox proportional hazard model. Institutional costs for the evaluated postdischarge events were compared via multivariate linear regression analysis. In the first 12 months after index hospital discharge, the risk of all-cause rehospitalization and ER use was significantly lower in the paliperidone palmitate cohort than in the oral antipsychotic cohort (hazard ratio, 0.61; 95% confidence interval [CI], 0.59-0.63; p < 0.0001); institutional costs during the first 6 months after discharge were significantly lower in the paliperidone palmitate cohort than in the comparator group (adjusted mean monthly cost difference -$404; 95% CI, -$781 to -$148; p < 0.0001). The use of paliperidone palmitate therapy during patients' index hospital admission for schizophrenia was associated with a reduced risk of hospital readmission or ER use and lower postdischarge institutional costs. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Prognostic Significance of the Number of Positive Lymph Nodes in Women With T1-2N1 Breast Cancer Treated With Mastectomy: Should Patients With 1, 2, and 3 Positive Lymph Nodes Be Grouped Together?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dai Kubicky, Charlotte, E-mail: charlottedai@gmail.com; Mongoue-Tchokote, Solange

2013-04-01

Purpose: To determine whether patients with 1, 2, or 3 positive lymph nodes (LNs) have similar survival outcomes. Methods and Materials: We analyzed the Surveillance, Epidemiology, and End Results registry of breast cancer patients diagnosed between 1990 and 2003. We identified 10,415 women with T1-2N1M0 breast cancer who were treated with mastectomy with no adjuvant radiation, with at least 10 LNs examined and 6 months of follow-up. The Kaplan-Meier method and log–rank test were used for survival analysis. Multivariate analysis was performed using the Cox proportional hazard model. Results: Median follow-up was 92 months. Ten-year overall survival (OS) and cause-specificmore » survival (CSS) were progressively worse with increasing number of positive LNs. Survival rates were 70%, 64%, and 60% (OS), and 82%, 76%, and 72% (CSS) for 1, 2, and 3 positive LNs, respectively. Pairwise log–rank test P values were <.001 (1 vs 2 positive LNs), <.001 (1 vs 3 positive LNs), and .002 (2 vs 3 positive LNs). Multivariate analysis showed that number of positive LNs was a significant predictor of OS and CSS. Hazard ratios increased with the number of positive LNs. In addition, age, primary tumor size, grade, estrogen receptor and progesterone receptor status, race, and year of diagnosis were significant prognostic factors. Conclusions: Our study suggests that patients with 1, 2, and 3 positive LNs have distinct survival outcomes, with increasing number of positive LNs associated with worse OS and CSS. The conventional grouping of 1-3 positive LNs needs to be reconsidered.« less

Intentional Weight Loss and Endometrial Cancer Risk.

PubMed

Luo, Juhua; Chlebowski, Rowan T; Hendryx, Michael; Rohan, Thomas; Wactawski-Wende, Jean; Thomson, Cynthia A; Felix, Ashley S; Chen, Chu; Barrington, Wendy; Coday, Mace; Stefanick, Marcia; LeBlanc, Erin; Margolis, Karen L

2017-04-10

Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women's Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.

Risk of falling in a stroke unit after acute stroke: The Fall Study of Gothenburg (FallsGOT).

PubMed

Persson, Carina U; Kjellberg, Sigvar; Lernfelt, Bodil; Westerlind, Ellen; Cruce, Malin; Hansson, Per-Olof

2018-03-01

This study aimed to investigate incidence of falls and different baseline variables and their association with falling during hospitalization in a stroke unit among patients with acute stroke. Prospective observational study. A stroke unit at a university hospital. A consecutive sample of stroke patients, out of which 504 were included, while 101 declined participation. The patients were assessed a mean of 1.7 days after admission and 3.8 days after stroke onset. The primary end-point was any fall, from admission to the stroke unit to discharge. Factors associated with falling were analysed using univariable and multivariable Cox hazard regression analyses. Independent variables were related to function, activity and participation, as well as personal and environmental factors. In total, 65 patients (13%) fell at least once. Factors statistically significantly associated with falling in the multivariable analysis were male sex (hazard ratio (HR): 1.88, 95% confidence interval (CI): 1.13-3.14, P = 0.015), use of a walking aid (HR: 2.11, 95% CI: 1.24-3.60, P = 0.006) and postural control as assessed with the modified version of the Postural Assessment Scale for Stroke Patients (SwePASS). No association was found with age, cognition or stroke severity, the HR for low SwePASS scores (⩽24) was 9.33 (95% CI: 2.19-39.78, P = 0.003) and for medium SwePASS scores (25-30) was 6.34 (95% CI: 1.46-27.51, P = 0.014), compared with high SwePASS scores (⩾31). Postural control, male sex and use of a walking aid are associated with falling during hospitalization after acute stroke.

Adherence to recommendations of the German food pyramid and risk of chronic diseases: results from the EPIC-Potsdam study.

PubMed

von Ruesten, A; Illner, A-K; Buijsse, B; Heidemann, C; Boeing, H

2010-11-01

The German food pyramid was set up to foster and communicate healthy food choices. The adherence to recommendations of the food pyramid was translated into an index (German Food Pyramid Index (GFPI)) by scoring the ratio of consumed and recommended daily servings of eight food groups, wherein higher scores indicated greater adherence. The GFPI was calculated for 23 531 subjects who participated in the European Prospective Investigation into Cancer and Nutrition-Potsdam study and were recruited between 1994 and 1998. Associations between quintiles of GFPI scores and risk of incident cardiovascular diseases (CVD), type-2 diabetes (T2D) and cancer were evaluated using Cox proportional hazard regression models. During 183 740 person-years of follow-up, 363 incident cases of CVD (myocardial infarction or stroke), 837 incident cases of T2D and 844 incident cases of cancer occurred. The GFPI was inversely related to CVD risk in men (multivariable-adjusted hazard ratio (HR) for highest versus lowest quintiles=0.56; 95% confidence interval (CI): 0.34-0.94) but not in women (HR=1.39; 95% CI: 0.76-2.55). No association between GFPI and cancer was observed. An inverse relation between GFPI and T2D (men: HR= 0.71 (0.52-0.97); women: HR= 0.69 (0.50-0.96)) in age-adjusted models was substantially attenuated after multivariable adjustments, particularly by body mass index (BMI) (men: HR=0.94 (0.69-1.30); women: HR=1.09 (0.77-1.54)). The same was observed for overall major chronic disease risk (CVD, T2D and total cancer). Adherence to the German food pyramid recommendations is not associated with a decreased risk of chronic diseases when considering BMI as confounder, except of CVD in men.

Survival Following Radiation and Androgen Suppression Therapy for Prostate Cancer in Healthy Older Men: Implications for Screening Recommendations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Paul L., E-mail: pnguyen@LROC.harvard.ed; Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA; Chen, Ming-Hui

2010-02-01

Purpose: The U.S. Preventive Services Task Force has recommended against screening men over 75 for prostate cancer. We examined whether older healthy men could benefit from aggressive prostate cancer treatment. Methods and Materials: 206 men with intermediate to high risk localized prostate cancer randomized to 70 Gy of radiation (RT) or RT plus 6 months of androgen suppression therapy (RT+AST) constituted the study cohort. Within subgroups stratified by Adult Comorbidity Evaluation-27 comorbidity score and age, Cox multivariable analysis was used to determine whether treatment with RT+AST as compared with RT was associated with a decreased risk of death. Results: Amongmore » healthy men (i.e., with mild or no comorbidity), 78 were older than the median age of 72.4 years, and in this subgroup, RT+AST was associated with a significantly lower risk of death on multivariable analysis (adjusted hazard ratio = 0.36 (95% CI=0.13-0.98), p = 0.046, with significantly lower 8-year mortality estimates of 16.5% vs. 41.4% (p = 0.011). Conversely, among men with moderate or severe comorbidity, 24 were older than the median age of 73, and in this subgroup, treatment with RT+AST was associated with a higher risk of death (adjusted hazard ratio = 5.2 (1.3-20.2), p = 0.018). Conclusion: In older men with mild or no comorbidity, treatment with RT+AST was associated with improved survival compared with treatment with RT alone, suggesting that healthy older men may derive the same benefits from prostate cancer treatment as younger men. We therefore suggest that prostate cancer screening recommendations should not be based on strict age cutoffs alone but should also take into account comorbidity.« less

Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease.

PubMed

Sargent, Julia; Muzzi, Ruthnea; Mukherjee, Rajat; Somarathne, Sharlene; Schranz, Katherine; Stephenson, Hannah; Connolly, David; Brodbelt, David; Fuentes, Virginia Luis

2015-03-01

To evaluate vena contracta and other echocardiographic measures of myxomatous mitral valve disease (MMVD) severity in a multivariable analysis of survival in dogs. 70 dogs diagnosed with MMVD from stored echocardiographic images that met study inclusion criteria. Left heart dimensions were measured as well as mitral regurgitant jet area/left atrial area (JAR), early mitral filling velocity (Evel), extent of mitral valve prolapse in right and left views (ProlR, ProlL), Prol indexed to aortic diameter (ProlR:Ao, ProlL:Ao), presence of a flail leaflet (FlailR, FlailL), and mitral regurgitation vena contracta diameter (VCR, VCL) indexed to aortic diameter (VCR:Ao, VCL:Ao). Follow-up from referring veterinarians was obtained by questionnaire or telephone to determine survival times. Inter- and intra-observer agreement was evaluated with Bland-Altman plots and weighted Kappa analysis. Survival was analyzed using Kaplan-Meier curves, logrank tests and Cox's proportional hazards. Logrank analysis showed VCL:Ao, VCR:Ao, FlailL, ProlR:Ao, ProlL:Ao, left ventricular internal dimension in diastole indexed to aortic diameter (LVIDD:Ao) >2.87, left atrium to aorta ratio (LA/Ao) >1.6, and Evel >1.4 m/s were predictors of cardiac mortality. In a multivariable analysis, the independent predictors of cardiac mortality were Evel >1.4 m/s [hazard ratio (HR) 5.0, 95% confidence interval (CI) 2.5-10.3], FlailL (HR 3.1, 95% CI 1.3-7.9), and ProlR:Ao (HR 2.8, 95% CI 1.3-6.3). Echocardiographic measures of mitral regurgitation severity and mitral valve pathology provide valuable prognostic information independent of chamber enlargement in dogs with MMVD. Copyright © 2014 Elsevier B.V. All rights reserved.

Overexpression of MutSα Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma.

PubMed

Wagner, Vivian Petersen; Webber, Liana Preto; Salvadori, Gabriela; Meurer, Luise; Fonseca, Felipe Paiva; Castilho, Rogério Moraes; Squarize, Cristiane Helena; Vargas, Pablo Agustin; Martins, Manoela Domingues

2016-05-01

The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ± 15.21 and 31.46 ± 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.

Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

PubMed

Hwang, Ki-Tae; Kim, Eun-Kyu; Jung, Sung Hoo; Lee, Eun Sook; Kim, Seung Il; Lee, Seokwon; Park, Heung Kyu; Kim, Jongjin; Oh, Sohee; Kim, Young A

2018-06-01

To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

Early and late mortality of spontaneous hemorrhagic transformation of ischemic stroke.

PubMed

D'Amelio, Marco; Terruso, Valeria; Famoso, Giorgia; Di Benedetto, Norma; Realmuto, Sabrina; Valentino, Francesca; Ragonese, Paolo; Savettieri, Giovanni; Aridon, Paolo

2014-04-01

Hemorrhagic transformation (HT), a complication of ischemic stroke (IS), might influence patient's prognosis. Our aim is to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and mortality. We compared mortality of individuals with spontaneous HT with that of individuals without. Medical records of patients diagnosed with anterior IS were retrospectively reviewed. Outcome measures were 30- and 90-day survival after IS onset. Kaplan-Meier estimates were used to construct survival curves. Cox proportional hazards model was used to estimate hazard ratio (HR) for the main outcome measure (death). HT was stratified in hemorrhagic infarction and parenchymal hematoma (PH). We also evaluated the relationship between HT and the main mortality risk factors (gender, age, premorbid status, severity of stroke, and radiological features). Thirty days from stroke onset, 8.1% (19 of 233) of patients died. At multivariate analysis, PH (HR: 7.7, 95% confidence interval [CI]: 2.1, 27.8) and low level of consciousness at admission (HR: 5.0, 95% CI: 1.3, 18.6) were significantly associated with death. At 3-month follow-up, mortality rate was 12.1% (28 of 232). At multivariate analysis, large infarct size (HR: 2.7, 95% CI: 1.2, 6.0) and HT (HR: 2.3, 95% CI: 1.0, 5.4) were independent risk factors for mortality. Parenchymal hematoma was, however, the strongest predictor of late mortality (HR: 7.9, 95% CI: 2.9, 21.4). Neurological status and infarct size play a significant role, respectively, in early and late mortality after IS. Parenchymal hematoma independently predicts both early and late mortality. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Short Sleep Duration is an Independent Predictor of Cardiovascular Events in Japanese Hypertensive Patients

PubMed Central

Eguchi, Kazuo; Pickering, Thomas G.; Schwartz, Joseph E.; Hoshide, Satoshi; Ishikawa, Joji; Ishikawa, Shizukiyo; Shimada, Kazuyuki; Kario, Kazuomi

2013-01-01

Context It is not known whether short duration of sleep is a predictor of future cardiovascular events in hypertensive patients. Objective To test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD). Design, Setting, and Participants We performed ambulatory BP monitoring (ABPM) in 1255 subjects with hypertension (mean age: 70.4±9.9 years) and they were followed for an average of 50±23 months. Short sleep duration was defined as <7.5 hrs (20th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio (HR) and 95% CI for short sleep duration. A riser pattern was defined when average nighttime SBP exceeded daytime SBP. Main Outcome Measures The end point was cardiovascular events: stroke, fatal or non-fatal myocardial infarction (MI), and sudden cardiac death. Results In multivariable analyses, short duration of sleep (<7.5 hrs) was associated with incident CVD (HR=1.68; 1.06–2.66, P=.03). A synergistic interaction was observed between short sleep duration and the riser pattern (P=.089). When subjects were categorized on the basis of their sleep time and riser/non-riser patterns, the shorter sleep+riser group had a substantially and significantly higher incidence of CVD than the predominant normal sleep+non-riser group (HR=4.43;2.09–9.39, P<0.001), independent of covariates. Conclusions Short duration of sleep is associated with incident CVD risk, and the combination of riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of hypertensive patients. PMID:19001199

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

PubMed

Swords, Douglas S; Mulvihill, Sean J; Skarda, David E; Finlayson, Samuel R G; Stoddard, Gregory J; Ott, Mark J; Firpo, Matthew A; Scaife, Courtney L

2017-07-11

To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

Pathologic Predictors of Survival During Lymph Node Dissection for Metastatic Renal-Cell Carcinoma: Results From a Multicenter Collaboration.

PubMed

Chipollini, Juan; Abel, E Jason; Peyton, Charles C; Boulware, David C; Karam, Jose A; Margulis, Vitaly; Master, Viraj A; Zargar-Shoshtari, Kamran; Matin, Surena F; Sexton, Wade J; Raman, Jay D; Wood, Christopher G; Spiess, Philippe E

2018-04-01

To determine the therapeutic value of lymph node dissection (LND) during cytoreductive nephrectomy (CN) and assess predictors of cancer-specific survival (CSS) in metastatic renal-cell carcinoma. We identified 293 consecutive patients treated with CN at 4 academic institutions from March 2000 to May 2015. LND was performed in 187 patients (63.8%). CSS was estimated by the Kaplan-Meier method for the entire cohort and for a propensity score-matched cohort. Cox proportional hazards regression was used to evaluate CSS in a multivariate model and in an inverse probability weighting-adjusted model for patients who underwent dissection. Median follow-up was 12.6 months (interquartile range, 4.47, 30.3), and median survival was 15.9 months. Of the 293 patients, 187 (63.8%) underwent LND. One hundred six patients had nodal involvement (pN+) with a median CSS of 11.3 months (95% confidence interval [CI], 6.6, 15.9) versus 24.2 months (95% confidence interval, 14.1, 34.3) for pN- patients (log-rank P = .002). The hazard ratio for LND was 1.325 (95% CI, 1.002, 1.75) for the whole cohort and 1.024 (95% CI, 0.682, 1.537) in the propensity score-matched cohort. Multivariate analysis revealed that number of positive lymph nodes (P < .001) was a significant predictor of worse CSS. For patients with metastatic renal-cell carcinoma undergoing CN with lymphadenectomy, the number of nodes positive was predictive of survival at short-term follow-up. However, nonstandardized lymphadenectomy only provided prognostic information without therapeutic benefit. Prospective studies with standardized templates are required to further ascertain the therapeutic value of LND. Copyright © 2017 Elsevier Inc. All rights reserved.